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Sample records for clear cell renal-cell

  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. 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

  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. 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

  5. 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

  6. 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

  7. 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

  8. 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 ...

  9. 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.

  10. 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.

  11. 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.

  12. 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

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

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

    2015-05-01

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

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

    NARCIS (Netherlands)

    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

  15. 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...

  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. 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

  18. 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

  19. 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

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

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    Weber T

    2014-05-01

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

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

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

    Science.gov (United States)

    Bhatnagar, Ramneesh; Alexiev, Borislav A

    2012-02-01

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

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

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    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.

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

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    Almeida, Catarina Faria de

    2013-01-01

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

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

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    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.

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

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    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

  7. 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.

  8. 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

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

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    Mijušković Mirjana

    2016-01-01

    Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

  10. 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

  11. 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

  12. 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

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

    Science.gov (United States)

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

    2015-09-01

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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  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. 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

  5. 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

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  13. 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. 

  14. 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.

  15. 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

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

    Science.gov (United States)

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

    2015-09-15

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

  17. 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

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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

  3. 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.

  4. [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

  5. 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

  6. 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

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

    Science.gov (United States)

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

    2016-10-01

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

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.)....

  3. 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

  4. 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.

  5. 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

  6. 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....

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  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. 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 ...

  19. 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

  20. 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....

  1. Renal cell carcinoma: links and risks

    Directory of Open Access Journals (Sweden)

    Kabaria R

    2016-03-01

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

  2. 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.

  3. Bilateral acrometastasis in a case renal cell carcinoma

    Science.gov (United States)

    Vaishya, Raju; Vijay, Vipul; Vaish, Abhishek

    2014-01-01

    We present a unique case of bilateral skeletal metastasis below the knee in a patient with renal cell carcinoma. In this rarest of rare cases, bony metastases were the first presentation of a primary tumour. Incidentally, the primary tumour (renal cell carcinoma) involved the solitary kidney of the patient and the same patient also had coexisting carcinoma of the prostate. PMID:25368128

  4. 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...

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. [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

  15. 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....

  16. 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.)

  17. 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

  18. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fengju Chen

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

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

  1. 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.

  2. 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.

  3. Perfusion computed tomography in renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  4. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

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

    2012-10-01

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

  5. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

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

  6. 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...

  7. 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 ...

  8. 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...

  9. 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

  10. 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.

  11. 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

  12. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  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. {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.)

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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

  5. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

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    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.

  6. 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

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

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    Rombo, Roman

    2016-04-01

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

  8. 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 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...

  9. 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.

  10. 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...

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  13. 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.)....

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Georgios Kravvas

    2014-01-01

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

  1. 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

  2. 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.

  3. 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.

  4. Surgical Treatment of Pancreatic Metastases of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Oncogenic micro-RNAs and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cristina eGrange

    2014-03-01

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

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

    Directory of Open Access Journals (Sweden)

    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 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...

  10. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  20. 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.

  1. 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.

  2. [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.

  3. 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

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    Isabella Dash

    2010-12-01

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

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Thomas C. Wehler

    2008-01-01

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

  9. 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

  10. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    Directory of Open Access Journals (Sweden)

    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.

  11. Tivozanib in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hepgur M

    2013-06-01

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

  12. 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

  13. 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.

  14. 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 ...

  15. 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

  16. 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

  17. 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.

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

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    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.

  19. 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.

  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. 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.

  2. 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

  3. 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.

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

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    Sumanta K. Pal

    2015-01-01

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

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

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    Rachna Raman

    2015-01-01

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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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

  15. 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)

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    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.

  16. 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.

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

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

    2005-12-01

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

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

    Directory of Open Access Journals (Sweden)

    2005-12-01

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

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    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 above indices into the MSKCC scale revealed that the groups were prognostically heterogeneous. The median survival in patients with good prognosis was 36.2 months (50.3, 38.3, and 24.5 months in those with 0—1, 2—3, and more than 3 immunological factors, respectively and in those with relatively good and poor prognosis it was 15.3 (29.1, 15.3, and 18.1 months and 8.5 (12.1, 9.3, and 6.3 months months, respectively.Conclusion. The cytokine status reflects the aggressiveness of a tumor process. The cytokine level changes may be used to predict the out- come of the disease.  

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

    Directory of Open Access Journals (Sweden)

    O. E. Molchanov

    2014-08-01

    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 above indices into the MSKCC scale revealed that the groups were prognostically heterogeneous. The median survival in patients with good prognosis was 36.2 months (50.3, 38.3, and 24.5 months in those with 0—1, 2—3, and more than 3 immunological factors, respectively and in those with relatively good and poor prognosis it was 15.3 (29.1, 15.3, and 18.1 months and 8.5 (12.1, 9.3, and 6.3 months months, respectively.Conclusion. The cytokine status reflects the aggressiveness of a tumor process. The cytokine level changes may be used to predict the out- come of the disease.  

  2. 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.

  3. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  5. 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.

  6. 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.

  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. 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.

  9. The clinicalapplication of interleukin-2therapy in patients withmetastatic renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Wen Zhou

    2015-01-01

    Objective: To analyze the clinical application of interleukin-2 therapy in patients with metastatic renal cell carcinoma.Methods:From January 2010 to July 2014 of 108 patients with metastatic renal cell carcinoma patients in our hospital as research subjects were randomly divided into the experimental group and the control group. The experimental group received IL-2 combined with Nexavar therapy, and the control group only received Nexavar treatment, clinical efficacy and incidence of adverse reactions between the two groups of patients were compared.Results:Compared with the control group, clinical efficacy in the experimental group was significantly higher, the difference was statistically significant. The incidence of adverse events was higher in patients than that in the experimental group, the difference was statistically significant, but IL-2 had no new adverse reactions and side effects.Conclusions:Interleukin-2 combined with Nexavar treatment of metastatic renal cell carcinoma can improve the clinical efficacy of metastatic renal cell carcinoma in patients, and ease the patient's condition from worsening and promote the quality of life. However, adverse reactions caused by drugs were inevitable; we should pay attention to treatment and prevention of adverse reactions in order to improve the quality of life of patients with metastatic renal cell carcinoma.

  10. 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.

  11. 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.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Concurrent renal-cell carcinoma and cutaneous leiomyomas: A case of HLRCC

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    Sara A. Fondriest, BS

    2015-01-01

    Full Text Available A 51-year-old Caucasian female presenting with renal-cell cancer and cutaneous leiomyomas was later diagnosed with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC Syndrome. HLRCC is an autosomal dominant condition caused by a mutation in the fumarate hydratase gene, which encodes for an enzyme in the citric acid cycle. This syndrome has been reported in over 100 families throughout the world, the majority of whom are of Eastern European descent. Those with this syndrome have a significantly increased risk of developing renal-cell carcinoma, cutaneous leiomyomas, and uterine leiomyomas, and a smaller chance of developing uterine leiomyosarcomas. This syndrome has a relatively poor prognosis, with tumor metastasis occurring in approximately 50% of patients. However, more aggressive prophylactic measures and recent studies have shown potential to improve patient prognosis.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-09-01

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

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

    Directory of Open Access Journals (Sweden)

    J. P. Barras

    1996-01-01

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

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

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    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.

  3. 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.)

  4. Expression of mitochondrial fission protein locus Fisl and ultrastructural changes in the renal cells of rats with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    秦双立

    2013-01-01

    Objective To observe the expression of mitochondrial fission protein locus Fis1 and ultrastructural changes in the renal cells of rats with chronic fluorosis,and to reveal the mechanism in mitochondrial damage of the renal cells.Methods Sixty SD rats were randomly divided into 3 groups according

  5. 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

  6. 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

  7. 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.

  8. 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

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  10. Clear cell chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. 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...

  12. 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

  13. Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands

    NARCIS (Netherlands)

    Mihajlović, J.; Minović, I.; Bruinsma, A.; Postma, M.J.

    2013-01-01

    Objectives: Metastatic renal cell cancer (mRCC) is becoming an important part of Dutch health care expenditure due to expensive pharmaceutical options for disease control and lack of adequate prevention methods. New targeted therapeutics, such as sunitinib, sorafenib and everolimus, have recently em

  14. Balancing treatment efficacy, toxicity and complication risk in elderly patients with metastatic renal cell carcinoma

    NARCIS (Netherlands)

    van den Brom, R R H; van Es, S C; Leliveld, A M; Gietema, J A; Hospers, G A P; de Jong, I J; de Vries, E G E; Oosting, S F

    2016-01-01

    The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients

  15. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

    NARCIS (Netherlands)

    Patard, J.J.; Leray, E.; Rioux-Leclercq, N.; Cindolo, L.; Ficarra, V.; Zisman, A.; Taille, A. De La; Tostain, J.; Artibani, W.; Abbou, C.C.; Lobel, B.; Guille, F.; Chopin, D.K.; Mulders, P.F.A.; Wood, C.G.; Swanson, D.A.; Figlin, R.A.; Belldegrun, A.S.; Pantuck, A.J.

    2005-01-01

    PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Hist

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  19. 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.

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

    NARCIS (Netherlands)

    T.M. Reijke; J. Bellmunt; H. van Poppel; S. Marreaud; M. Aapro

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    Directory of Open Access Journals (Sweden)

    S. Malde

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  5. Cruciferous vegetables consumption and risk of renal cell carcinoma: a meta-analysis.

    Science.gov (United States)

    Liu, Ben; Mao, Qiqi; Wang, Xiao; Zhou, Feng; Luo, Jindan; Wang, Chaojun; Lin, Yiwei; Zheng, Xiangyi; Xie, Liping

    2013-01-01

    Previous cohort and case-control studies on the association between cruciferous vegetables consumption and risk of renal cell carcinoma have illustrated conflicting results so far. To demonstrate the potential association between them, a meta-analysis was performed. Eligible studies were retrieved via both computerized searches and review of references. The summary relative risks (RRs) with 95% confidence interval (CI) for the highest vs. the lowest consumption of cruciferous vegetables were calculated. Heterogeneity and publication bias were also evaluated. Stratified analyses were performed as well. Three cohort and 7 case-control studies were included. A significantly decreased risk with renal cell carcinoma was observed in overall cruciferous vegetables consumption group (RR = 0.73; 95% CI, 0.63-0.83) and subgroup of case-control studies (RR = 0.69; 95% CI, 0.60-0.78), but not in cohort studies (RR = 0.96; 95% CI, 0.71-1.21). No heterogeneity and publication bias were detected across studies. Our findings supported that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma. Because of the limited number of studies, further well-designed prospective studies and researches need to be conducted to better clarify the protective effect of cruciferous vegetables on renal cell carcinoma and potential mechanism.

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

    Directory of Open Access Journals (Sweden)

    Michael Kongnyuy

    2015-01-01

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

  7. 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

  8. 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.

  9. 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.

  10. [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.)

  11. 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

  12. 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)

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  15. 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.

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

    Science.gov (United States)

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

    2016-01-01

    ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. PMID:27564279

  17. 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.

  18. Reversible Posterior Leukoencephalopathy Syndrome Developing After Restart of Sunitinib Therapy for Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Shinji Fukui

    2016-01-01

    Full Text Available A 64-year-old Japanese man had started molecular-targeted therapy with sunitinib for lymph node metastasis 5 years after nephrectomy for left renal cell carcinoma (clear cell carcinoma, G2, pT2N0M0. He was transported to our emergency department because of generalized tonic-clonic seizure, vision loss, and impaired consciousness with acute hypertension after 8 cycles of treatment (2 years after the initiation of sunitinib therapy, including a drug withdrawal period for one year. MRI of the brain (FLAIR images showed multiple high-intensity lesions in the white matter of the occipital and cerebellar lobes, dorsal brain stem, and left thalamus. Reversible posterior leukoencephalopathy syndrome caused by sunitinib was suspected. In addition to the immediate discontinuation of sunitinib therapy, the administration of antihypertensive agents and anticonvulsants improved the clinical symptoms without neurological damage. Physicians should be aware that sunitinib causes reversible posterior leukoencephalopathy syndrome. The early recognition of reversible posterior leukoencephalopathy syndrome is critical to avoid irreversible neurological damage.

  19. 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

  20. 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

  1. 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

  2. Pancreatic metastases from renal cell carcinoma: The state of the art

    Institute of Scientific and Technical Information of China (English)

    Roberto Ballarin; Giuseppe D'Amico; Giorgio Enrico Gerunda; Fabrizio Di Benedetto; Mario Spaggiari; Nicola Cautero; Nicola De Ruvo; Roberto Montalti; Cristina Longo; Anna Pecchi; Patrizia Giacobazzi; Giuseppina De Marco

    2011-01-01

    Pancreatic metastases are rare, with a reported inci-dence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. Howev-er, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

  3. Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?

    Directory of Open Access Journals (Sweden)

    Asim Amin

    2014-11-01

    Full Text Available Modulation of the immune response plays an important role in the natural history of renal cell carcinoma.  Spontaneous regression of metastases has been well documented in a small percentage of patients after they undergo de-bulking nephrectomy without any additional systemic intervention.  The only logical explanation for these observations is “resetting” of the balance between tumor and the host immune system that, having been overwhelmed by the tumor burden, is able to function better after tumor de-bulking.  Attempts to modulate the activity of the immune system “on demand” have included the use of vaccines, cytokines/lymphokines, adoptive cell transfer, monoclonal antibodies and most recently manipulation of immune checkpoint inhibitors.  Here we review the data for infusional interleukin-2 in the management of advanced renal cell carcinoma and its role in current clinical practice.

  4. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Wang Yong

    2013-02-01

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

  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. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    with a DC- based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...

  11. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn;

    2008-01-01

    with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

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

    2012-01-01

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

  14. Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

    LENUS (Irish Health Repository)

    Curry, Sarah

    2012-02-01

    The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

  15. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-11

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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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. 

  19. 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. 

  20. Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?

    OpenAIRE

    Asim Amin; White, Richard L.

    2014-01-01

    Modulation of the immune response plays an important role in the natural history of renal cell carcinoma.  Spontaneous regression of metastases has been well documented in a small percentage of patients after they undergo de-bulking nephrectomy without any additional systemic intervention.  The only logical explanation for these observations is “resetting” of the balance between tumor and the host immune system that, having been overwhelmed by the tumor burden, is able to function better afte...

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2005-01-01

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

  3. Evaluating the safety and efficacy of axitinib in the treatment of advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Gunnarsson O

    2015-02-01

    Full Text Available Orvar Gunnarsson,1 Nicklas R Pfanzelter,2 Roger B Cohen,1 Stephen M Keefe1 1Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 2Department of Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor-α, and c-kit. Phase I studies demonstrated 5 mg twice daily as the recommended starting dose with notable effects seen in renal cell carcinoma, an observation confirmed in Phase II trials. The trial of comparative effectivess of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS was an international randomized Phase III study designed for registration purposes, compared axitinib to sunitinib. This trial randomized 723 patients with metastatic kidney cancer to axitinib or sunitinib in the second-line setting and demonstrated a median progression-free survival of 6.7 months for axitinib versus 4.7 months for sorafenib (P<0.0001. Clinical benefit was detected regardless of prior therapy, but no overall survival benefit has been observed. Axitinib is well tolerated without a significant effect on quality of life. The most common grade 3 toxicities are hypertension (16%, diarrhea (11%, and fatigue (11%, with other notable side effects being anorexia, nausea, hand–foot syndrome, and rash. Patients who developed diastolic blood pressure >90 mmHg were noted to have significantly longer median overall survival and overall response rates when compared to normotensive patients. Therefore, the manufacturer recommends escalating the twice-daily dose to 7 mg and 10 mg, as tolerated, if there is no significant increase in blood pressure on treatment. Currently, axitinib is approved for use in the second-line setting for patients with metastatic renal cell carcinoma. Research is ongoing in other disease

  4. 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...

  5. 8-year survival in a patient with several recurrences of renal cell carcinoma after radical nephrectomy

    OpenAIRE

    Joshi, Shivam; Eldefrawy, Ahmed; Ciancio, Gaetano

    2012-01-01

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

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

    Science.gov (United States)

    Bukowski, Ronald M

    2009-05-15

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

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

    Directory of Open Access Journals (Sweden)

    Majd Alfreijat

    2016-10-01

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

  8. The occult nature of intramedullary spinal cord metastases from renal cell carcinoma.

    LENUS (Irish Health Repository)

    Zakaria, Zaitun

    2012-01-01

    Renal cell carcinomas (RCC) are characterised by a tendency to metastasise widely, often while remaining occult. Intramedullary spinal cord metastases (ISCM) from RCC may be the presenting feature of the disease or present at any time in the disease course. This case report discusses an ISCM from RCC which became manifested at the time of resection of the primary tumour. We review the literature published on ISCM from RCC from 1990 to date comparing disease characteristics and presentations.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. 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 ...

  11. Genome-wide methylation analysis of tubulocystic and papillary renal cell carcinomas.

    Science.gov (United States)

    Korabecna, M; Geryk, J; Hora, M; Steiner, P; Seda, O; Tesar, V

    2016-01-01

    Tubulocystic renal cell carcinoma (TRCC) represents a rare tumor with incidence lower than 1 % of all renal carcinomas. This study was undertaken to contribute to characterization of molecular signatures associated with TRCC and to compare them with the features of papillary renal cell carcinoma (PRCC) at the level of genome wide methylation analysis.We performed methylated DNA immunoprecipitation (MeDIP) coupled with microarray analysis (Roche NimbleGen). Using the CHARM package, we compared the levels of gene methylation between paired samples of tumors and control renal tissues of each examined individual. We found significant global demethylation in all tumor samples in comparison with adjacent kidney tissues of normal histological appearance but no significant differences in gene methylation between the both compared tumor entities. Therefore we focused on characterization of differentially methylated regions between both tumors and control tissues. We found 42 differentially methylated genes.Hypermethylated genes for protocadherins (PCDHG) and genes coding for products associated with functions of plasma membrane were evaluated as significantly overrepresented among hypermethylated genes detected in both types of renal cell carcinomas.In our pilot study, we provide the first evidence that identical features in the process of carcinogenesis leading to TRCC and/or to PRCC may be found at the gene methylation level.

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

    Directory of Open Access Journals (Sweden)

    Priluck JC

    2012-11-01

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

  13. Renal Cell Carcinoma Mimicking Igg4-Related Pseudotumor in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2014-09-01

    Full Text Available Context Autoimmune pancreatitis is classified into two distinct clinical profiles. Care report Type 1 autoimmunepancreatitis (AIP is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosingdisease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bileducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevationof IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile ductstrictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. Conclusion Wepresent a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

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

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten;

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indic...

  15. Renal cell carcinoma presenting as a solitary cutaneous facial metastasis: case report and review of the literature

    OpenAIRE

    Porter, Neil A; Anderson, Helen L; Al-Dujaily, Saad

    2006-01-01

    Background Renal cell carcinoma is well known for its frequency to metastasise, particularly to lungs, liver, bones and brain. Metastasis to the skin is much less common. Presentation as a result of the skin lesion is even more unusual, with only 14 previously reported cases in the English literature. The majority of these cases have been reported in patients with recurrent disease or with other metastases. Case presentation We present only the second case of non-recurrent renal cell carcinom...

  16. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2010-01-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

  17. THE AUTHOR’S EXPERIENCE IN USING BEVACIZUMAB PLUS INTERFERON ALFA-2A IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2014-08-01

    Full Text Available Target therapy is a main approach to treating metastatic renal cell carcinoma. Bevacizumab plus interferon alfa-2A is now standard first-line options for patients with previously untreated, good or intermediate prognosis (using the Memorial Sloan-Kettering Cancer Center criteria. We have presented our experience in using bevacisumab plus interferon alfa-2A in patients with metastatic renal cell carcinoma. Median progression-free survival and overall survival were 10 months and 22 months, respectively.

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

    Science.gov (United States)

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

    2013-08-01

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

  19. Surgical management of renal cell carcinoma with inferior vena caval thrombus: A teaching hospital experience

    Directory of Open Access Journals (Sweden)

    Kulkarni Jagdeesh

    2007-01-01

    Full Text Available Purpose: To evaluate the outcome of patients of renal cell carcinoma (RCC with inferior vena caval (IVC thrombus treated by radical nephrectomy and IVC thrombectomy in terms of clinical and pathological factors and prognosis. Materials and Methods: Sixty-three consecutive patients of RCC with IVC thrombus who underwent radical nephrectomy with IVC thrombectomy between June 1993 and May 2003 were included in this retrospective analysis. Data was analyzed in terms of clinical factors, such as level of thrombus, and pathological factors, such as grade, local invasion and N status. Results: Tumor thrombus level was infrahepatic in 35 patients, retrohepatic in 20 and suprahepatic in 8, including 5 with right atrial thrombus. The immediate post-operative mortality was 3%, and the incidence of major post-operative complications was 34%, but most of them improved after conservative management except one who needed surgery for burst abdomen. The disease free survival (DFS was 48.5%, 50.6%, 66.6% and 40% for infrahepatic, retrohepatic, suprahepatic and intra-atrial tumors, respectively. Of the histological types, patients with clear cell tumors had the best prognosis; those with granular cell had the worst prognosis (DFS of 53.5% vs 33.3%, though statistically not significant. Grade-2 tumors had better prognosis than grade-4 tumors (DFS 66.6% vs 0%, P < 0.001. Sixty-eight percent of patients without perinephric fat invasion were free of disease as compared to 31% of those with perinephric fat invasion (P < 0.01. Further, N status showed DFS of 60.9% in patients with negative nodes and 30% in patients with positive nodes (P < 0.05. Conclusion: Though surgery for RCC with IVC thrombus has high morbidity, it can give good results in terms of prolonged DFS in expert hands. Regarding long-term survival, pathological factors, such as local stage and grade, are more important than clinical factors, such as level of thrombus.

  20. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Steven M Yip

    2016-03-01

    Full Text Available 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 database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

  1. Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Xue-song; ZHANG Zheng; ZHANG Qian; WANG Gang; HE Zhi-song; ZHOU Li-quan; JIN Jie; WU Xiang; ZHAO Peng-ju; HUANG Li-hua; SONG Yi; GONG Kan; SHEN Cheng YU Wei; SONG Gang; ZHAO Zheng

    2011-01-01

    Background The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.Methods A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.Results The median follow-up was 15 months (10 cycles, range 1.5-30.0 months (1-20 cycles)). Ten patients (29.4%)achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting >2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0-28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7-24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

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

  4. 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.

  5. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... the major advances in the characterization and application of TIL therapy for patients with RCC and OC....... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-31

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

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

    Directory of Open Access Journals (Sweden)

    Pasupuleti Santhosh Kumar

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Andres Borja Alvarez

    2015-01-01

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

  11. 肾嫌色细胞癌临床特征分析%Clinical features on chromophobe renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王志华; 杜立环; 胡志全; 陈先国; 赵霞; 王少刚; 庄乾元; 叶章群

    2011-01-01

    Objectives To explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma. Methods From January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations,treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis. Results All cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases,pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free.The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63. 8% and 49. 9% at the same periods, and there is no difference in the survival rate of five years( P > 0. 05

  12. Overexpression of Csk-binding protein contributes to renal cell carcinogenesis.

    Science.gov (United States)

    Feng, X; Lu, X; Man, X; Zhou, W; Jiang, L Q; Knyazev, P; Lei, L; Huang, Q; Ullrich, A; Zhang, Z; Chen, Z

    2009-09-17

    C-terminal Src kinase (Csk)-binding protein (Cbp) is a transmembrane adaptor protein that localizes exclusively in lipid rafts, where it regulates Src family kinase (SFK) activities through recruitment of Csk. Although SFKs are well known for their involvement in cancer, the function of Cbp in carcinogenesis remains largely unknown. In this study, we reported overexpression of Cbp in more than 70% of renal cell carcinoma (RCC) specimens and in the majority of tested RCC cell lines. Depletion of Cbp in RCC cells by RNA interference led to remarkable inhibition of cell proliferation, migration, anchorage-independent growth as well as tumorigenicity in nude mice. Strikingly, silencing of Cbp negatively affected the sustaining of Erk1/2 activation but not c-Src activation induced by serum. Besides, the RhoA activity in RCC cells was remarkably impaired when Cbp was knocked down. Overexpression of wild-type Cbp, but not its mutant Cbp/DeltaCP lacking C-terminal PDZ-binding motif, significantly enhanced RhoA activation and cell migration of RCC cells. These results provided new insights into the function of Cbp in modulating RhoA activation, by which Cbp might contribute to renal cell carcinogenesis. PMID:19581936

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

    OpenAIRE

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

    2013-01-01

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

  14. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael;

    2014-01-01

    , stage, performance status and white cell blood count were related to poor OS. Using multivariate analyses to adjust for risk predictors the difference in OS disappeared. Median OS before and after introduction of TKIs was 16 months and 14 months, respectively (p = 0.189). Memorial Sloan Kettering Cancer......Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

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

    Directory of Open Access Journals (Sweden)

    Clara E. Jäkel

    2012-01-01

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

  16. The Presence of Recipient-Derived Renal Cells in Kidney Allografts

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    Türkan METE

    2011-09-01

    Full Text Available OBJECTIVE: Stem cells may be involved in the repair processes of renal tissues during various disorders. We aimed to search the presence of recipient originated cells in renal allograft tissues from patients with various types of allograft dysfunction including acute rejection, acute tubular necrosis, calcineurin inhibitor toxicity, and chronic rejection. MATERIAL and METHODS: Eleven kidney transplant recipients were enrolled in the study. Seven patients who had sex-mismatched donors were regarded as the study group and the remaining were the controls (male-male, positive controls, n=2; female-female, negative controls, n=2. Histopathological examinations in the study group had revealed chronic rejection in four patients(together with calcineurin inhibitor toxicity in three and acute rejection, acute tubular necrosis, and cyclosporine toxicity in one patient each. Deparaffi nised biopsy specimens were examined using chromogenic in situ hybridization (CISH method for the XY cocktail probe. RESULTS: Renal cells of positive controls had XY, whereas those of negative controls had XX chromosomal signals. Examination of the biopsy samples from the study group showed variable ratios of recipient-derived tubular(2-76%, interstitial mesenchymal(5-83%, and endothelial cells(1-53%. CONCLUSION: The presence of recipient-derived renal cells in injured kidney allografts suggests that there is a possible dynamic interaction between allograft and stem cells of the recipient. Further studies are needed to clarify the origin and the function of these cells.

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anatoly Nikolaev

    2016-01-01

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

  20. COMBINED TREATMENT OF RENAL CELL CARCINOMA METASTASIS LOCATED IN THE HUMERUS WITH RECONSTRUCTIVE PLASTIC SURGERY STAGE

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    S. A. Ivanov

    2014-01-01

    Full Text Available In the recent years, the effectiveness of the treatment of even advanced cases of metastatic renal cell carcinoma is relatively high due to the possibility of targeted therapy, removal of metastatic lesions. Therefore, the issue of the quality of life of such patients often comes to the fore. This paper presents a clinical case of radical surgical treatment of metastasis located in the humerus, resulting in partial recovery of the limb function which eventually led to the improvement of the patient’s quality of life.

  1. Sorafenib-induced hand-foot syndrome in a patient of renal cell carcinoma

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    Amrita Sil

    2014-01-01

    Full Text Available Sorafenib, a multikinase inhibitor, is approved for treatment of renal cell cancer and hepatocellular cancer. Hand-foot syndrome (HFD is a condition where erythema, scaling, and bullous lesion affect the hand and feet. In this case, a post-nephrectomy renal carcinoma patient prescribed sorafenib developed HFD 1 week after the drug usage. All laboratory parameters were within normal limits. The dose of sorafenib was reduced and topical corticosteroids, antihistamines, and emollients were prescribed. The reaction reduced after 2 weeks of therapy, only to reappear again when the second cycle of sorafenib-targeted therapy was started. The case was diagnosed as sorafenib-induced HFD.

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

    Science.gov (United States)

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

    2010-10-01

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

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

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    Andrew T. Schlussel

    2013-01-01

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

  4. Fish, Vitamin D, and Flavonoids in Relation to Renal Cell Cancer Among Smokers

    OpenAIRE

    Wilson, Robin Taylor; Wang, Jiangyue; Chinchilli, Vernon; Richie, John P.; Virtamo, Jarmo; Moore, Lee E.; Albanes, Demetrius

    2009-01-01

    Fish, vitamin D, flavonoids, and flavonoid-containing foods may have cardiovascular benefits and therefore may also reduce the risk of renal cell cancer. Risk was prospectively assessed in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (1985–2002) cohort (N = 27,111; 15.2 mean person-years of follow-up). At enrollment, demographic, health, and dietary history information was recorded. Individuals who smoked less than 5 cigarettes/day, with chronic renal insufficiency or prior canc...

  5. 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

  6. Metastases of Renal Cell Carcinoma to the Thyroid Gland with Synchronous Benign and Malignant Follicular Cell-Derived Neoplasms

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    Carlos Zamarrón

    2013-01-01

    Full Text Available Clear cell renal cell carcinoma (CCRCC is the most common origin for metastasis in the thyroid. A 51-year-old woman was referred to our hospital for a subcarinal lesion. Ten years before, the patient had undergone a nephrectomy for CCRCC. Whole-body fluorodeoxyglucose positron emission tomography revealed elevated values in the thyroid gland, while the mediastinum was normal. An endoscopic ultrasonography-guided fine-needle aspiration biopsy of the mediastinal mass was consistent with CCRCC, and this was confirmed after resection. The thyroidectomy specimen also revealed lymphocytic thyroiditis, nodular hyperplasia, one follicular adenoma, two papillary microcarcinomas, and six foci of metastatic CCRCC involving both thyroid lobes. Curiously two of the six metastatic foci were located inside two adenomatoid nodules (tumor-in-tumor. The metastatic cells were positive for cytokeratins, CD10, epidermal growth factor receptor, and vascular endothelial growth factor receptor 2. No BRAF gene mutations were found in any of the primary and metastatic lesions. The patient was treated with sunitinib and finally died due to CCRCC distant metastases 6 years after the thyroidectomy. In CCRCC patients, a particularly prolonged survival rate may be achieved with the appropriate therapy, in contrast to the ominous prognosis typically found in patients with thyroid metastases from other origins.

  7. Renal cell carcinomas with t(6;11)(p21;q12) presenting with tubulocystic renal cell carcinoma-like features.

    Science.gov (United States)

    Rao, Qiu; Zhang, Xiu-Mei; Tu, Pin; Xia, Qiu-Yuan; Shen, Qin; Zhou, Xiao-Jun; Shi, Qun-Li

    2013-01-01

    In this study, we reported an additional genetically confirmed case of renal cell carcinomas (RCCs) with t(6;11)(p21;q12) showing an unusual histological pattern. Histologically, the tumor was entirely composed of small to intermediate sized tubules and cysts. The tubules and cysts were lined by a single layer of flat, hobnail, cuboidal to columnar epithelial cells. Most cells demonstrated abundant eosinophilic cytoplasm with regular, round or oval nuclei and some inconspicuous nucleoli. All these morphological features are suggestive of tubulocystic carcinoma of the kidney. However, the tumor demonstrated moderately (2+) or strongly (3+) positive staining for TFEB, Cathepsin K, Ksp-cadherin, and vimentin but negative for TFE3, CD10, HMB45, melan A, CKpan, and CK7. Using a recently developed TFEB split FISH assay, the presence of TFEB rearrangement was demonstrated. Our results support the clinical application of a TFEB break-apart FISH assay for diagnosis and confirmation of TFEB RCC and further expand the morphologic spectrum that may be present in these neoplasms, sometimes raising a challenging differential diagnosis with other renal tumors.

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

    Science.gov (United States)

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

    2010-09-01

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

  9. Bisphenol S Interacts with Catalase and Induces Oxidative Stress in Mouse Liver and Renal Cells.

    Science.gov (United States)

    Zhang, Rui; Liu, Rutao; Zong, Wansong

    2016-08-31

    Bisphenol S (BPS) is present in multitudinous consumer products and detected in both food and water. It also has been a main substitute for bisphenol A (BPA) in the food-packaging industry. Yet, the toxicity of BPS is not fully understood. The present study of the toxicity of BPS was divided into two parts. First, oxidative stress, cell viability, apoptosis level, and catalase (CAT) activity in mouse hepatocytes and renal cells were investigated after BPS exposure. After 12 h of incubation with BPS, all of these parameters of hepatocytes and renal cells changed by >15% as the concentration of BPS ranged from 0.1 to 1 mM. Second, the direct interaction between BPS and CAT on the molecule level was investigated by multiple spectral methods and molecular docking investigations. BPS changed the structure and the activity of CAT through binding to the Gly 117 residue on the substrate channel of the enzyme. The main binding forces were hydrogen bond and hydrophobic force. PMID:27508457

  10. Bisphenol S Interacts with Catalase and Induces Oxidative Stress in Mouse Liver and Renal Cells.

    Science.gov (United States)

    Zhang, Rui; Liu, Rutao; Zong, Wansong

    2016-08-31

    Bisphenol S (BPS) is present in multitudinous consumer products and detected in both food and water. It also has been a main substitute for bisphenol A (BPA) in the food-packaging industry. Yet, the toxicity of BPS is not fully understood. The present study of the toxicity of BPS was divided into two parts. First, oxidative stress, cell viability, apoptosis level, and catalase (CAT) activity in mouse hepatocytes and renal cells were investigated after BPS exposure. After 12 h of incubation with BPS, all of these parameters of hepatocytes and renal cells changed by >15% as the concentration of BPS ranged from 0.1 to 1 mM. Second, the direct interaction between BPS and CAT on the molecule level was investigated by multiple spectral methods and molecular docking investigations. BPS changed the structure and the activity of CAT through binding to the Gly 117 residue on the substrate channel of the enzyme. The main binding forces were hydrogen bond and hydrophobic force.

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

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    Bodnar Lubomir

    2009-10-01

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

  12. Coexistence of a colon carcinoma with two distinct renal cell carcinomas: a case report

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    Giannopoulos Lambros A

    2011-04-01

    Full Text Available Abstract Introduction We present the case of a patient with two tumors in his left kidney and a synchronous colon cancer. While coexisting tumors have been previously described in the same kidney or the kidney and other organs, or the colon and other organs, to the best of our knowledge no such concurrency of three primary tumors has been reported in the literature to date. Case presentation A 72-year-old man of Greek nationality presenting with pain in the right hypochondrium underwent a series of examinations that revealed gallstones, a tumor in the hepatic flexure of the colon and an additional tumor in the upper pole of the left kidney. He was subjected to a right hemicolectomy, left nephrectomy and cholecystectomy, and his postoperative course was uneventful. Histopathology examinations showed a mucinous colon adenocarcinoma, plus two tumors in the left kidney, a papillary renal cell carcinoma and a chromophobe renal cell carcinoma. Conclusion This case underlines the need to routinely scan patients pre-operatively in order to exclude coexisting tumors, especially asymptomatic renal tumors in patients with colorectal cancer, and additionally to screen concurrent tumors genetically in order to detect putative common genetic alterations.

  13. Flexibility and efficacy of automatic continuous fluorodeoxyuridine infusion in metastases from a renal cell carcinoma.

    Science.gov (United States)

    Damascelli, B; Marchianò, A; Frigerio, L F; Salvetti, M; Spreafico, C; Garbagnati, F; Zanoni, F; Radice, F

    1991-09-01

    Complete and lasting control of diffuse metastases from a renal cell carcinoma has been achieved by automatic continuous infusion of a single cytotoxic agent, fluorodeoxyuridine (FUDR). A patient with a single brain metastasis from renal cell carcinoma developed pulmonary, mediastinal, and retroperitoneal metastases after radical nephrectomy. A Medtronic Synchromed pump (Medtronic Inc., Minneapolis, MN) was implanted for the circadian systemic infusion of FUDR in 14-day courses with 14-day drug-free intervals. A complete response (CR) at all sites, was obtained in 3 months, and maintained for 22 months. After a second brain metastasis, treated by radiation therapy and cisplatin as radiosensitizer, a CR was obtained again and is now of 31 months' duration, which is four times the record to date. The overall hospitalization was 2 days. Acceptance of the pump is excellent and it functions precisely and reliably. This case should stimulate greater interest in techniques of automatic continuous infusion of cytostatics, given its greater efficacy and lower toxicity. PMID:1833043

  14. Macroamylasemia with a markedly increased amylase clearance ratio in a patient with renal cell carcinoma.

    Science.gov (United States)

    Kazmierczak, S C; Van Lente, F; McHugh, A M; Katzin, W E

    1988-02-01

    We report hyperamylasemia, macroamylasemia, and a markedly increased amylase clearance/creatinine clearance ratio in a patient with renal cell carcinoma. Serum amylase activity was characterized as macroamylase by gel exclusion chromatography. Electrophoretic separation revealed an atypical band of amylase, migrating anodal to the S2 control fraction. Electrophoresis of urine revealed the presence of both S1 and S2 fractions, but not the atypical band found in serum. Quantification of the salivary- and pancreatic-type amylase fractions showed amylase in urine to be 100% salivary. Immunofixation disclosed the macroamylase to consist of an immune complex between amylase and IgA-lambda antibody. Binding-capacity studies showed that the serum immunoglobulin was present in excess and could bind 46% and 49% additional S-type amylase activity derived from saliva and the patient's urine, respectively. The amylase clearance/creatinine clearance ratio was markedly supranormal (0.134), unexpected in a patient with macroamylasemia. A biopsy specimen of the renal cell tumor was found to contain significant salivary-type amylase activity. These results suggest production of amylase by tumor tissue in the renal carcinoma and secretion of S-type amylase into the patient's urine. Evidently, macroamylase should be confirmed by gel exclusion chromatography.

  15. 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;}

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Karami Sara

    2012-08-01

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

  18. Immunotherapeutic strategies for the treatment of renal cell carcinoma: where are we now?

    Science.gov (United States)

    Bedke, Jens; Stenzl, Arnulf

    2013-12-01

    Immunotherapy with cytokines was the first effective treatment in metastatic renal cell carcinoma (mRCC). Long-term responders and complete remissions were observed, but efficacy in the overall population was limited with the consequence that targeted agents replaced cytokines. The discovery of tumor associated antigens as direct targets paved the way from theses rather unspecific to specific immunotherapeutic strategies, which are discussed in this review. Autologous or dendritic cell (DC) based tumor vaccination with vitespen or AGS-003, adoptive T-cell transfer and synthetic peptide vaccination with IMA901 are new and promising approaches. Besides that the more passive strategies of antibody dependent cytotoxicity with the VEGF antibody bevacizumab or the carbonic anhydrase IX antibody girentuximab are discussed. Immunomodulation by cyclophosphamide, tyrosine kinase inhibitors or nivolumab, which targets the PD-1 axis, further promote T-cell activation and combinatory strategies with these agents are outlined.

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

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    Shengqiang Xu

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

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

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    Meyer Werner

    2010-10-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.

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

    Science.gov (United States)

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

    2014-09-01

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

  2. Metastatic Renal Cell Carcinoma in the Thyroid Gland and Pancreas Showing Uptake on 68Ga DOTATATE PET/CT Scan.

    Science.gov (United States)

    Kanthan, Gowri L; Schembri, Geoffrey Paul; Samra, Jaswinder; Roach, Paul; Hsiao, Edward

    2016-07-01

    Ga DOTATATE PET/CT is an imaging technique used in the diagnosis of neuroendocrine tumors. We report a case of 66-year-old woman with a history of surgically removed renal cell carcinoma who presented for a DOTATATE PET/CT scan to characterize a newly diagnosed pancreatic lesion. DOTATATE-avid lesions were identified in the thyroid gland and pancreas. Subsequent biopsy confirmed the diagnosis of metastatic renal cell carcinoma at both sites. It is important to be aware that tumors other than neuroendocrine tumors may also show uptake on DOTATATE PET/CT scan. A biopsy may be required if lesions are identified at atypical sites. PMID:27055137

  3. Robot-assisted heminephrectomy for chromophobe renal cell carcinoma in L-shaped fused crossed ectopia: Surgical challenge.

    Science.gov (United States)

    Kumar, Santosh; Singh, Shivanshu; Jain, Siddharth; Bora, Girdhar Singh; Singh, Shrawan Kumar

    2015-10-01

    Renal cell carcinoma associated with fused ectopic kidneys has rarely been reported in the literature. Here we report the first case of robot-assisted heminephrectomy for chromophobe renal cell carcinoma in an L-shaped fused ectopic kidney. The present case report highlights the importance of three-dimensional vision and enhanced maneuverability with the EndoWrist technology of the robotic surgical system for precise dissection. This report also highlights the importance of preoperative contrast-enhanced computed tomography with three-dimensional arterial reconstruction for surgical planning. PMID:26495075

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

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    Susan Yung

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

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

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    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC model established in our laboratory. Methods The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. Results In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-20

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

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

    Science.gov (United States)

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

    2016-08-01

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

  9. IMMUNOMODULATORY EFFECTS OF INTRAVENOUS BIS-1 F(AB')(2) ADMINISTRATION IN RENAL-CELL CANCER-PATIENTS

    NARCIS (Netherlands)

    JANSSEN, RAJ; KROESEN, BJ; MESANDER, G; SLEIJFER, DT; THE, TH; MULDER, NH; DELEIJ, L

    1995-01-01

    We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

  10. Histological and immunohistochemical characterization of feline renal cell carcinoma: a case series.

    Science.gov (United States)

    Bonsembiante, Federico; Benali, Silvia Lucia; Trez, Davide; Aresu, Luca; Gelain, Maria Elena

    2016-07-01

    Four feline renal cell carcinomas (RCCs) were examined using histopathological and immunohistochemical procedures. Specimens were classified by predominant histological pattern according to WHO criteria. A panel of antibodies including β-catenin, C-KIT, VEGF and VEGF-R2 and double immunostaining for vimentin/cytokeratin and for E-cadherin/CD10 was selected to characterize the tumors. Neoplasms were classified as tubular (3/4) and papillary (1/4). Neoplastic epithelial cells were cytokeratin, vimentin, E-cadherin, VEGF-R2 positive and C-KIT negative; 3 cases were β-catenin positive, whereas only 2 tumors were CD10 and VEGF positive. No correlation with histotype was evident. Our results confirm the low frequency of RCCs in cats and suggest a histological pattern similar to canine RCCs. In contrast, a peculiar immunohistochemical profile different from both canine and human RCCs is identified. PMID:26888581

  11. CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS IN A RAT MODEL OF HEREDITARY RENAL CELL CARCINOMA

    Science.gov (United States)

    Carcinogenicity of Individual and a Mixture of Drinking Water Disinfection By-Products in a Rat Model of Hereditary Renal Cell Carcinoma Eker rats develop hereditary renal cell carcinoma secondary to a germline mutation in the tuberous sclerosis 2 (Tsc2) gene and are ligh...

  12. A new staging system for locally advanced (pT3-4) renal cell carcinoma: a multicenter European study including 2,000 patients.

    NARCIS (Netherlands)

    Ficarra, V.; Galfano, A.; Guille, F.; Schips, L.; Tostain, J.; Mejean, A.; Lang, H.; Mulders, P.F.A.; Taille, A. De La; Chautard, D.; Descotes, J.L.; Cindolo, L.; Novara, G.; Rioux-Leclercq, N.; Zattoni, F.; Artibani, W.; Patard, J.J.

    2007-01-01

    PURPOSE: We provide an adequate prognostic stratification for locally advanced renal cell carcinoma and propose a new TNM classification. MATERIALS AND METHODS: We analyzed clinical and pathological data on a large series of patients undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 1

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    Amishi Y. Shah

    2015-03-01

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

  15. 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.

  16. 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.

  17. [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

  18. Large cystic renal cell carcinoma leading to diagnostic dilemma: a case report.

    Science.gov (United States)

    Amar, V; Vennapusa, B; Kumar, M Mahendra; Nagaraju, B; Srinivas, G; Bhargav, P R K

    2013-06-01

    Large cystic renal tumours can be confused with hepatic lesions even on crosssectional imaging. Careful clinical, sonographic and imaging analysis is needed for establishing correct diagnosis. We report a case of papillary cystic renal carcinoma in a 60 year old man, which was confused with amoebic liver abcess and was initially drained. Subsequent recurrence of symptoms prompted us to re-evaluate the case and repeat sonography confirmed the extrahepatic origin of mass based on simple observation that the liver and mass were moving separately on inspiration. Later guided aspiration from solid component of the mass confirmed the diagnosis as renal cell carcinoma. He was successfully treated with radical nephrectomy with uneventful post-operative recovery. PMID:24426529

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

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-07-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  1. Cases of Renal Cell Carcinoma and Lung Metastasis Sequential Bilateral Pneumothorax

    Directory of Open Access Journals (Sweden)

    Mahmut Tokur

    2013-07-01

    Full Text Available The metastasis of the lungs develop in proportion as 30% of all cancers. Spontaneous pneumothorax is a rarely found but clinically significant complication in lung and trachea tumors. Spontaneous pneumothorax may also occur in metastatic tumors. Different levels of dispnea are observed in metastatic lung tumors according to the prevalance of the lesions. Sudden or progressive incline in the shortness of breath in these patients may be the harbinger of a spontaneous pneumothorax. In this presentation, underwent left nephrectomy with a diagnosis of renal cell carcinoma, bilateral pulmonary metastases after nephrectomy for two years due to the development of spontaneous pneumothorax in consecutive patients given chemotherapy was discussed with the development of literature.

  2. 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.

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

    Science.gov (United States)

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

    2016-11-01

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

  4. Remission of psoriasis and psoriatic arthritis during bevacizumab therapy for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Ananaya Datta-Mitra

    2014-01-01

    Full Text Available Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF, is employed for treatment of several cancers and retinopathies. Although previous reports of remission of psoriasis with bevacizumab do exist, but its current experience for psoriatic arthritis (PsA is still limited. In this report, we describe a patient with metastatic renal cell cancer, psoriasis and PsA, who experienced a complete remission of psoriasis and PsA during bevacizumab therapy without any other management for psoriasis and PsA. We also found a flare up of his psoriatic disease after switching to other kinase inhibitors like sorafenib or sunitinib. This suggests that bevacizumab might have a promising future in the treatment of psoriasis and PsA.

  5. A middle-aged man with a history of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Garciaorr R

    2011-06-01

    Full Text Available A 56 year old man was seen with a lung nodule. He had an extensive past medical history including renal cell carcinoma, congestive heart failure, obstructive sleep apnea and a 135 pack-year history of smoking. His physical examination was consistent with congestive heart failure. Sputum cultures for bacteria, fungi and tuberculosis were all negative. A CT scan revealed a spiculated, noncalcified 2.1 mass in the right lower lobe. PET scan showed the lesion to have a standard uptake value of 1.5. The lesion was followed and after 3 months had enlarged to 6.4 cm. Biopsy was done and consistent with a lung abscess. Conservative therapy resulted in resolution only to have the lesion recur 22 months later with the patient expiring from massive hemoptysis and respiratory failure. This case illustrates the usefulness of doubling time in separating benign from malignant lung lesions.

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2...... (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration......, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients...

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Bukowski RM

    2011-08-01

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

  9. Complications of ultrasound-guided percutaneous microwave ablation of renal cell carcinoma

    Science.gov (United States)

    Dong, Xuejuan; Li, Xin; Yu, Jie; Yu, Ming-an; Yu, Xiaoling; Liang, Ping

    2016-01-01

    Purpose To retrospectively review the complications of ultrasound (US)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma. Patients and methods In this study, 101 patients with 105 tumors seen from April 2006 to Feb 2014 were enrolled retrospectively. The patients were treated with US-guided percutaneous MWA and were followed up with contrast-enhanced US and computed tomography or magnetic resonance imaging at 1, 3, and 6 months and every 6 months thereafter. Results Technical success was achieved in 99 of 105 tumors (94.3%). The median follow-up time was 25 (range 1.13–93.23) months. Among the 105 tumors, 26 complications in 24.8% of patients and 23 minor complications (Clavien–Dindo Grades I and II) in 21.9% of patients were noted, accounting for 88.5% of all complications. All the minor complications were cured. Three major complications (Clavien–Dindo Grade ≥III) occurred in 2.9% of the patients, accounting for 11.5% of all complications: hydrothorax in two patients and bowel injury in one. The two patients who had hydrothorax post-MWA had a history of cirrhosis and were treated with catheter drainage. The bowel injury was treated surgically. In all patients, the changes in serum creatinine and urea nitrogen levels from before to after the procedure were small. Conclusion US-guided percutaneous MWA is a beneficial treatment for renal cell carcinoma in selected patients; however, if the renal tumor is close to the bowel, or the patient has serious comorbidities or has undergone abdominal surgery, the procedure must be performed more carefully. PMID:27713644

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  11. Cost-effectiveness of targeted therapeutics in metastatic renal cell cancer seen from two different economic perspectives

    NARCIS (Netherlands)

    Mihajlović, J.; Postma, M.J.

    2014-01-01

    Objectives: To assess the cost-effectiveness of first line metastatic renal cell cancer (mRCC) drugs from the perspective of two different economic and clinical settings, The Netherlands (NL) and Serbia (SRB). Methods: The research included all first line mRCC therapeutics recommended by the Europea

  12. Validation of an integrated staging system toward improved prognostication of patients with localized renal cell carcinoma in an international population.

    NARCIS (Netherlands)

    Han, K.R.; Bleumer, I.; Pantuck, A.J.; Kim, H.L.; Dorey, F.J.; Janzen, N.K.; Zisman, A.; Dinney, C.P.; Wood, C.G.; Swanson, D.A.; Said, J.W.; Figlin, R.A.; Mulders, P.F.A.; Belldegrun, A.S.

    2003-01-01

    PURPOSE: Outcome prediction for patients with renal cell carcinoma is based on a combination of factors. In this study a previously published clinical outcome algorithm based on 1997 T stage, Fuhrman grade and performance score is validated using an international database. MATERIALS AND METHODS: A t

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  14. PHASE-I STUDY OF INTRAVENOUSLY APPLIED BISPECIFIC ANTIBODY IN RENAL-CELL CANCER-PATIENTS RECEIVING SUBCUTANEOUS INTERLEUKIN-2

    NARCIS (Netherlands)

    KROESEN, BJ; SLEIJFER, DT; JANSSEN, RAJ; VANDERGRAAF, WTA; THE, TH; DELEIJ, L; MULDER, NH

    1994-01-01

    In a phase I trial the toxicity and immunomodulatory effects of combined treatment with intravenous (i.v.) bispecific monoclonal antibody BIS-1 and subcutaneous (s.c.) interleukin 2 (IL-2) was studied in renal cell cancer patients. BIS-1 combines a specificity against CD3 on T lymphocytes with a spe

  15. Renal cell carcinomas with t(6;11) (p21;q12): presentation of two cases with computed tomography findings.

    Science.gov (United States)

    Zhao, YiJun; Yao, Jin; Chen, Ni; Zeng, Hao; Zhang, Wei

    2015-06-01

    Renal cell carcinomas with t(6;11) (p21;q12) translocation are extremely rare and primarily affect children and young adults. To our knowledge, there has been no case report focusing on the imaging manifestations in the existing literature. Hence, we describe the computed tomography findings of two young adults.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  17. Radioimmunotheapy with [I-131]cG250 in patients with metastasized renal cell cancer : Dosimetric analysis and immunologic response

    NARCIS (Netherlands)

    Brouwers, AH; Buijs, WCAM; Mulders, PFA; de Mulder, PHM; van den Broek, WJM; Mala, C; Oosterwijk, E; Boerman, OC; Corstens, FHM; Oyen, WJG

    2005-01-01

    Purpose: A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [I-131]cG250 in patients with metastasized renal cell carcinoma. Here, we report the dosimetric analysis and the relationship between the developme

  18. Molecular cytogenetic analysis of clustered sporadic and familial renal cell carcinoma-associated 3q13 approximately q22 breakpoints.

    NARCIS (Netherlands)

    Bodmer, D.; Janssen, I.M.; Jonkers, Y.M.H.; Berg, E. van den; Dijkhuizen, T.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.; Geurts van Kessel, A.H.M.

    2002-01-01

    We describe several relatives within one renal cell cancer (RCC) family sharing a constitutional t(2;3) (q35;q21). Based on molecular studies on several independent primary tumors in this family, a causative role for this translocation in tumor development was suggested. Subsequent positional clonin

  19. Biocompatibility of microplates for culturing epithelial renal cells evaluated by a microcalorimetric technique.

    Science.gov (United States)

    Xie, Y; DePierre, J W; Nässberger, L

    2000-09-01

    In the present study we have developed a microcalorimetric procedure which allows convenient investigation of biocompatibility in a microsystem. We examined the biocompatibility of a porcine renal epithelial tubule cell line LLC-PK1 and a human primary renal epithelial tubule cell (RPTEC) with microplates composed of three different materials, i.e. Thermanox, transparent film and titanium. All three materials showed equal biocompatibility with LLC-PK1 cells, judging from the attainment of steady-state power curves and the same rate of heat production per cell (2.5 microW / microg DNA). The human renal cells were poorly biocompatible with the Thermanox and transparent film. However, on titanium the RPTEC cell did adhere, as demonstrated by a steady-state power curve. The human cells also showed a higher metabolic activity (3.0 microW / microg DNA), than did LLC-PK1 cells cultured on the same type of microplates. In research on biocompatibility there is a need for alternatives to experimental animal investigations. The present technique allows studies of cellular interactions with different biomaterials in a rapid and standardized manner and may therefore prove to be a useful screening procedure. PMID:15348389

  20. The Place of Enucleation and Enucleo-Resection in the Treatment of Pancreatic Metastasis of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Thierry Yazbek

    2012-07-01

    Full Text Available Context Renal cell carcinoma has shown less response to systemic therapies including chemotherapy, radiotherapy andimmunotherapy than other cancers. Metastasis of renal cell carcinoma to the pancreas occurs, even after long term radicalnephrectomy, surgical resection remains the only potentially curative intervention. We performed surgery for pancreatic metastatic renal cell carcinoma and analyzed the results. Methods We retrospectively analyzed 11 patients who had undergone pancreatic resection or metastasectomy at our hospital from January 1994 to January 2010. Patient’s demographics, clinical variables, types of pancreatic resections (standard or atypical resection, primary histopathology, surgical outcomes, survival and disease free interval were examined. We compared the standard pancreatic resection to atypical resection (enucleation or enucleo-resection. Results Eleven patients underwent 14 pancreatic resections or metastasectomy (3 pancreaticoduodenectomy, 4 distal pancreatectomy, 1 completion of pancreatectomy, 4 enucleations and two enucleo-resections for pancreatic renal cell carcinoma metastasis. The median age was 73 years, the median time period between nephrectomy and finding of pancreatic metastasis was 11.4 years. One patient showed synchronous pancreatic metastatic lesions on radiology. One patient died from a splenic artery pseudoaneurysm rupture 35 days after the surgery. Major complications occurred in 4 patients with standard resection (one hemoperitoneum, three pancreatic fistulas, and in one patient with atypical resection (duodenal fistula; six patients with standard resection presented postoperative diabetes mellitus. Median survival age was 6.5 years (range 1-9 years. Two patients died of metastatic disease 5 to 6years, while 7 patients are alive and well 1 to 9 years after surgery. Conclusions According to these results and regardless of the small number of cases, atypical resection of metastatic renal cell

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

    Directory of Open Access Journals (Sweden)

    Xiaoguang Zhou

    2014-12-01

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

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

    International Nuclear Information System (INIS)

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

  3. Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by Downregulating Klotho Gene Expression.

    Science.gov (United States)

    Troyano-Suárez, Nuria; del Nogal-Avila, María; Mora, Inés; Sosa, Patricia; López-Ongil, Susana; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruíz-Torres, María Piedad

    2015-01-01

    Cellular senescence can be prematurely induced by oxidative stress involved in aging. In this work, we were searching for novel intermediaries in oxidative stress-induced senescence, focusing our interest on integrin-linked kinase (ILK), a scaffold protein at cell-extracellular matrix (ECM) adhesion sites, and on the Klotho gene. Cultured renal cells were treated with glucose oxidase (GOx) for long time periods. GOx induced senescence, increasing senescence associated β-galactosidase activity and the expression of p16. In parallel, GOx increased ILK protein expression and activity. Ectopic overexpression of ILK in cells increased p16 expression, even in the absence of GOx, whereas downregulation of ILK inhibited the increase in p16 due to oxidative stress. Additionally, GOx reduced Klotho gene expression and cells overexpressing Klotho protein did not undergo senescence after GOx addition. We demonstrated a direct link between ILK and Klotho since silencing ILK expression in cells and mice increases Klotho expression and reduces p53 and p16 expression in renal cortex. In conclusion, oxidative stress induces cellular senescence in kidney cells by increasing ILK protein expression and activity, which in turn reduces Klotho expression. We hereby present ILK as a novel downregulator of Klotho gene expression. PMID:26583057

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

  7. Radiation-induced glioma following CyberKnife® treatment of metastatic renal cell carcinoma: a case report

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    Abedalthagafi Malak

    2012-09-01

    Full Text Available Abstract Introduction Post-stereotactic radiation-induced neoplasms, although relatively rare, have raised the question of benefit regarding CyberKnife® treatments versus the risk of a secondary malignancy. The incidence of such neoplasms arising in the nervous system is thought to be low, given the paucity of case reports regarding such secondary lesions. Case presentation Here we describe a case of a 43-year-old Middle Eastern woman with primary clear cell renal cell carcinoma and a metastatic focus to the left brain parenchyma who presented with focal neurologic deficits. Following post-surgical stereotactic radiation in the region of the brain metastasis, the patient developed a secondary high-grade astrocytoma nearly 5 years after the initial treatment. Conclusion Although the benefit of CyberKnife® radiotherapy treatments continues to outweigh the relatively low risk of a radiation-induced secondary malignancy, knowledge of such risks and a review of the literature are warranted.

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

    Science.gov (United States)

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

    2015-01-01

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

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

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    Santosh Kumar Mondal

    2014-01-01

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

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

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    Peirong Chen

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

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

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    Patterson John R

    2008-09-01

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

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

    Science.gov (United States)

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

    2014-05-01

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

  13. 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

  14. Correlation between coagulation function, tumor stage and metastasis in patients with renal cell carcinoma: a retrospective study

    Institute of Scientific and Technical Information of China (English)

    XIAO Bo; MA Lu-lin; ZHANG Shu-dong; XIAO Chun-lei; LU Jian; HONG Kai; LIAO Hong-yi

    2011-01-01

    Background The coagulation function in carcinoma patients is abnormal, but in renal cell carcinoma the extent and relationships of coagulation function remain unclear. This study retrospectively investigated the relationships between coagulation function, clinical stage and metastasis in patients with renal cell carcinoma.Methods A total of 350 consecutive patients admitted to our Urology Department from 2004 to 2010 were diagnosed with renal cell carcinoma by histolopathologic examination and were included in this study. A total of 231 cases of renal benign tumors were considered as the control group. Fibrinogen, prothrombin time, activated partial thromboplastin time and international normalized ratio were evaluated in all subjects. Tumor size, clinical stage, lymph node metastasis, and distant metastasis were evaluated using radiologic imaging, intraoperative findings, and histological studies.Results The preoperative plasma fibrinogen levels of patients with renal cell carcinoma ((383.9±146.7) mg/dl) were significantly higher than those of the control group ((316.7±62.0) mg/dl) (P <0.01). We divided the renal cell carcinoma group into stages la, lb, Ⅱ, Ⅲ, and Ⅳ. The fibrinogen values were (315.6±64.6) mg/dl, (358.3±91.1) mg/dl, (465.6±164.7)mg/dl, (500.0±202.1) mg/dl, and (585.8±179.7) mg/dl, respectively. There were no significant differences in fibrinogen values between stage la and control groups. However, results of other stages showed significant differences when compared to control group values (P <0.01). Using the cutoff value of 440 mg/dl, which defines hyperfibrinogenemia,plasma fibrinogen levels had a positive predictive value of 39.8% and a negative predictive value of 93.3% for predicting distant metastasis, with a sensitivity of 64.7% and specificity of 83.3%.Concluslons Preoperative plasma fibrinogen levels are elevated in patients with renal cell carcinoma with distant metastasis or lymph node metastasis. Potential metastasis is

  15. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

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    T. Eisen

    2014-08-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

  16. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

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    T. Eisen

    2009-01-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

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

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    Quivy A

    2013-04-01

    Full Text Available Amandine Quivy,1,2 Amaury Daste,1 Asma Harbaoui,1 Sophie Duc,2,4 Jean-Christophe Bernhard,2,3 Marine Gross-Goupil,1 Alain Ravaud1,2 1Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France; 2University of Bordeaux 2 (Victor Ségalen, Bordeaux, France; 3Department of Urology, Hôpital Pellegrin, Bordeaux University Hospital, Bordeaux, France; 4Department of Geriatrics, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France Abstract: Both the aging population and the incidence of renal cell carcinoma (RCC are growing, making the question of tumor management in the elderly a real challenge. Doctors should be aware of the importance of assessing this specific subpopulation. An aggressive therapeutic approach may be balanced by the benefit of the treatment – care or cure – and the life expectancy and willingness of the patient. The treatment for local disease can be surgery (radical or partial nephrectomy or ablative therapies (radiofrequency, cryotherapy. Even if in most cases surgery is safe, complications such as alteration of renal function may occur, especially in the elderly, with physiological renal impairment at baseline. More recently, another option has been developed as an alternative: active surveillance. In the past decade, new drugs have been approved in the metastatic setting. All the phase 3 trials have included patients without a limit on age. Nevertheless, data concerning the elderly are still poor and concern only a very selective subpopulation. The toxicity profile of targeted agents may interfere with pre-existent comorbidities. Furthermore, the metabolism of several agents via cytochrome P450 can cause drug interaction. The importance of quality of life is a major factor with regard to management of therapy. Finally, to date, there is no recommendation of systematic a priori dose reduction in the elderly. In this review we describe the various possibilities of

  18. Carcinoma de células renais com metástase cutânea: relato de caso Renal cell carcinoma with cutaneous metastasis: case report

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    Thaís Alves de Paula

    2010-06-01

    Full Text Available O adenocarcinoma do rim, ou hipernefroma, é a terceira neoplasia mais comum do trato geniturinário, sendo o de células claras o tipo principal, representando 60% dos casos, com pico de incidência entre 50 e 70 anos. A presença de metástase ao diagnóstico acomete em torno de 30% dos pacientes, tendo como principais sítios pulmões, ossos, pele, fígado e cérebro. Relatamos o caso de um paciente portador de carcinoma de células renais com metástase ao diagnóstico que, apesar de inserido na faixa etária predominante, tipo histológico mais frequente e quadro clínico característico, apresentava metástase a distância em local pouco observado na prática clínica. O paciente evoluiu para o óbito sem tempo hábil para o tratamento.Renal cell carcinoma or hypernephroma is the third most common neoplasia of the genitourinary tract. Its most common type, representing 60% of the cases, is the clear cell carcinoma, with an incidence peak between 50 and 70 years. Metastases are present at the time of diagnosis in approximately 30% of the patients, the major sites being lungs, bones, skin, liver, and brain. We report the case of a male patient with renal cell carcinoma, whose age, clinical findings, and tumor histological type matched with the most common ones for that pathology. Nevertheless, he already had distant metastasis in an uncommon site at the time of diagnosis. The patient died without undergoing specific treatment for renal cell carcinoma.

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

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

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

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

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    Masataka Banshodani

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    曾进; 梅伟; 黄海鹏; 李晓东; 孔鹏

    2002-01-01

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

  3. {sup 18}F-FDG-PET/CT in Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Tae Joo [Pochon CHA University College of Medicine, Sungnam (Korea, Republic of)

    2008-12-15

    Renal cell carcinoma is the most common histological type of renal malignancy, predominant in men and the primary treatment modality of this tumor is surgery. The role of diagnostic imaging in the management of this tumor is the evaluation of extent of disease as well as the detection and characterization of renal mass. US has long been a routine screening tool for kidney but tomographic imaging modalities such as CT and MRI begin to be also commonly used these days. On the other hand, the sensitivity of 18F-FDG-PET in detection of renal mass is relatively low because of inherent limitation caused by FDG excretion pathway despite avid uptake of FDG to tumor cell per se. Many studies revealed FDG PET scan could play an important role in detection of metastatic lesions although the sensitivity for the detection of primary lesion is not so high. Furthermore, development of PET/CT scanner will make it possible to expand the indication of FDG PET scan in this malignancy.

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

    Directory of Open Access Journals (Sweden)

    Sinem Namdaroğlu

    2016-03-01

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

  5. Immunosuppression in murine renal cell carcinoma. I. Characterization of extent, severity and sources.

    Science.gov (United States)

    Gregorian, S K; Battisto, J R

    1990-01-01

    Four cell-mediated immunological responses related to tumor elimination have been examined in mice injected with a transplantable renal cell carcinoma (Renca). Lymphokine-activated killer (LAK) cells generated in vitro from spleen cells of normal mice were capable of attacking Renca, EL-4, P815 and YAC-1 targets, but those from mice bearing Renca for 3 weeks could not. Natural killer activity, stimulated in vivo by administering poly(I) poly(C), was less than 50% of normal in Renca-bearing hosts. In addition, development of cytotoxic T lymphocytes to allogeneic targets was markedly inhibited in mice possessing the renal tumor. Finally, the delayed hypersensitivity response to a dermally applied hapten was approximately 70% less than normal in tumor-bearing mice, no matter whether the tumor existed subcutaneously or intrarenally. A kinetic study of the development of non-responsiveness using the LAK assay showed onset of poor response at 1 week, which became maximal within 3 weeks following receipt of tumor subcutaneously. The immunological depression was seen to be attributable in part to suppressor cells present among spleen cells but not bone marrow cells of tumor-bearing hosts. The suppressor cells prevented in vitro LAK generation by normal spleen cells and, when adoptively transferred to normal mice, they inhibited natural killer stimulation and delayed hypersensitivity generation. Another source of immunological down-regulation was provided by Renca cells themselves. Incorporation of Renca cells that had been X-irradiated with 30,000 rad into cultures of normal and Renca-derived splenic cells suppressed replication of both almost completely. Furthermore, the presence of X-irradiated Renca cells in cultures of normal spleen cells prevented development of LAK cells. Thus, the suppression seen in Renca-bearing mice derives from multiple sources and whether each is in any way related to the other has been discussed. Identification of the phenotypes of cells

  6. 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

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

    Institute of Scientific and Technical Information of China (English)

    Shaoqi Wang; Shaoxiang Wang; Juan Wang

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zustovich F

    2011-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiao-fen Wu

    2016-06-01

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

  10. Role of Radiation Therapy in the Management of Renal Cell Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, Angel I.; Teh, Bin S. [Department of Radiation Oncology, The Methodist Hospital, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Department of Radiation Oncology, The Methodist Hospital, Houston, TX 77030 (United States); Amato, Robert J., E-mail: Robert.amato@uth.tmc.edu [Division of Oncology, University of Texas Health Science Center at Houston, Memorial Hermann Cancer Center, Houston, TX 77030 (United States)

    2011-10-26

    Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control.

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

    Science.gov (United States)

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

    2010-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yamanishi Tomonori

    2007-08-01

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

  14. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    Science.gov (United States)

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up.

  15. Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Pantaleo Maria

    2012-06-01

    Full Text Available Abstract Background Tyrosine kinase inhibitors (TKIs are currently approved for the treatment of metastatic renal cell carcinoma (mRCC. The cardiotoxic effects of sorafenib and sunitinib may cause hypertension, left ventricular ejection fraction (LVEF dysfunction and/or congestive heart failure (CHF, and arterial thrombo-embolic events (ATE. Only three cases of coronary artery disease related to sorafenib therapy have been described in the literature, and all were due to arterial vasospasm without evidence of coronary artery stenosis on angiography. Cardiotoxicity is commonly associated with the presence of cardiovascular risk factors, such as a history of hypertension or coronary artery disease. Case presentation We describe a patient who experienced an unusual cardiac event after 2 years of sorafenib treatment. A 58-year-old man with mRCC developed acute coronary syndrome (ischemia/infarction associated with critical sub-occlusion of the common trunk of the left coronary artery and some of its branches, which was documented on coronary angiography. The patient underwent triple coronary artery bypass surgery, and sorafenib treatment was discontinued. He did not have any cardiovascular risk factors, and his cardiac function and morphology were normal prior to sorafenib treatment. Conclusions Further investigation of a larger patient population is needed to better understand cardiac damage due to TKI treatment. Understanding the usefulness of careful cardiovascular monitoring might be important for the prevention of fatal cardiovascular events, and to avoid discontinuation of therapy for the underlying cancer.

  16. Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

    Science.gov (United States)

    Kollmannsberger, Christian; Bjarnason, Georg; Burnett, Patrick; Creel, Patricia; Davis, Mellar; Dawson, Nancy; Feldman, Darren; George, Suzanne; Hershman, Jerome; Lechner, Thomas; Potter, Amy; Raymond, Eric; Treister, Nathaniel; Wood, Laura; Wu, Shenhong; Bukowski, Ronald

    2011-01-01

    The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.

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

    Science.gov (United States)

    Bukowski, Ronald M

    2010-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

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

  20. Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump.

    Science.gov (United States)

    Damascelli, B; Marchianò, A; Spreafico, C; Lutman, R; Salvetti, M; Bonalumi, M G; Mauri, M; Garbagnati, F; Del Nero, A; Comeri, G

    1990-07-15

    The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life. PMID:2142443

  1. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    Science.gov (United States)

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up. PMID:27543869

  2. Role of Radiation Therapy in the Management of Renal Cell Cancer

    Directory of Open Access Journals (Sweden)

    Angel I. Blanco

    2011-10-01

    Full Text Available Renal cell carcinoma (RCC is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR inhibitors, to maximize both local and systemic control.

  3. Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

    Science.gov (United States)

    Amato, R J

    2005-01-01

    A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.

  4. Drug therapy of renal cell carcinoma%肾癌的药物治疗

    Institute of Scientific and Technical Information of China (English)

    康马飞

    2008-01-01

    肾癌的药物治疗目前仍以免疫化学治疗为主,单纯化疗也有效,吉西他滨联合顺铂是目前的标准化疗方案.靶向治疗药物的出现使肾癌的治疗发生了改变,多靶点受体酪氨酸激酶抑制剂(如舒尼替尼和索拉非尼)、哺乳动物雷帕霉素靶蛋白抑制剂(temsirolimus)和抗肿瘤单克隆抗体(如贝伐单抗)等已成为肾癌的一线治疗选择.%Immunochemotherapy is still the primary drug therapy of renal cell carcinoma(RCC), and chemotherapy is effective too. The combination of gemcitabine and cisplatin is the standard regimen now. How-ever, emerge of targeted therapeutic agents has altered the treatment of RCC. Multitargeted tyrosine kinase in-hibitor, such as sunitinib and sorafenib, and mammalian target of rapamycin (roTOR) inhibitors( temsiroll-mus), and anti-tumor monoclonal antibody, such as bevacizumab, have already become the first line election.

  5. Fruit, vegetables, fibre and micronutrients and risk of US renal cell carcinoma.

    Science.gov (United States)

    Brock, Kaye E; Ke, Liang; Gridley, Gloria; Chiu, Brian C-H; Ershow, Abby G; Lynch, Charles F; Graubard, Barry I; Cantor, Kenneth P

    2012-09-28

    The association between renal cell cancer (RCC) and intake of fruit, vegetables and nutrients was examined in a population-based case-control study of 323 cases and 1827 controls; dietary intake was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, proxy status, alcohol consumption and dietary fat intake and energy. Intake of vegetables was associated with a decreased risk of RCC (OR 0·5; 95 % CI 0·3, 0·7; P trend = 0·002), (top compared to the bottom quartile of intake). When intake of individual nutrients was investigated, vegetable fibre intake was associated with decreased risks (OR 0·4; 95 % CI 0·2, 0·6; P vegetable fibre and β-cryptoxanthin had significant trends (P vegetables and fruit fibre was also associated with increased risk of RCC (P interaction = 0·03); similar inverse associations were found for β-cryptoxanthin, lycopene and vitamin C. When nutrients were mutually adjusted by backwards regression in these subgroups, only β-cryptoxanthin remained associated with lower RCC risk. These findings deserve further investigation in ongoing prospective studies when sample size becomes sufficient.

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

    Directory of Open Access Journals (Sweden)

    Dorothee Pflueger

    2013-11-01

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

  7. Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine

    Directory of Open Access Journals (Sweden)

    Wittke S

    2016-01-01

    Full Text Available Stefan Wittke,1 Susann Baxmann,2 Dirk Fahlenkamp,3 Stephan T Kiessig2 1University of Applied Sciences Bremerhaven, Faculty of Biotechnology Bremerhaven, 2Ruhr-Plasma-Centre GmbH, Bochum, 3Department of Urology, Zeisigwald Bethanien Hospital, Chemnitz, Germany Purpose: An autologous tumor vaccine already used successfully in the immune therapy of renal cell carcinoma was investigated in detail. The evaluation of potential tumor markers should allow for the assessment of potency according to pharmaceutical regulations.Methods: A panel of 36 tumor-associated antigens and cellular marker proteins was characterized in a total of 133 tumor cell lysates by methods such as ELISA, Western blots, and topological proteomics. The induction of tumor-associated antigen-specific antibodies was demonstrated by immunization in mice.Results: Tumor heterogeneity was demonstrated: none of the tumor-associated antigens investigated were detectable in each tumor lysate. In parallel, the coincidental presence of potential danger signals was shown for HSP-60 and HSP-70. The presence of both antigen and danger signal allowed a successful induction of an immune response in a murine model.Conclusion: The verified tumor heterogeneity indicates the need for a multi-epitope approach for the successful immunotherapy in renal cell carcinoma. Keywords: renal cell carcinoma, kidney cancer, tumor-associated antigens, tumor marker, ELISA, Western Blot, immunotherapy, therapeutic vaccine, potency testing, topological proteomics

  8. Pediatric Papillary Renal Cell Carcinoma in a Horseshoe Kidney: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Abelardo Loya-Solis

    2015-01-01

    Full Text Available Renal cell carcinoma is the most common malignancy of the kidney in adults. In children, however, it only accounts for an estimated 1.8 to 6.3% of all pediatric malignant renal tumors. Papillary renal cell carcinoma is the second most common type of renal cell carcinoma in children. We present the case of a 12-year-old boy with a 2-month history of abdominal pain, unexplained weight loss, and gross hematuria. Computed tomography revealed a horseshoe kidney and a well-defined mass of 4 cm arising from the lower pole of the right kidney. Microscopically the tumor was composed of papillae covered with cells with abundant eosinophilic cytoplasm and high-grade nuclei with prominent nucleoli. Immunohistochemistry was performed; EMA, Vimentin, and AMACR were strongly positive while CK7, CD10, RCC antigen, TFE3, HMB-45, and WT-1 were negative. Currently, 10 months after the surgical procedure, the patient remains clinically and radiologically disease-free.

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

    OpenAIRE

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

    2011-01-01

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

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

    LENUS (Irish Health Repository)

    Cushen, Samantha J

    2014-04-21

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

  13. Castleman Disease in the Kidney and Retroperitoneum Mimicking Renal Cell Carcinoma with Retroperitoneal Lymphadenopathy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Hee Sun; Woo, Ji Young; Hong, Hye Suk; Jung, Ah Young; Yang, Ik; Lee, Yul [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    Castleman disease, or angiofollicular lymph node hyperplasia, is a fairly rare benign tumor of lymphoid origin with unknown etiology. Castleman disease arises mostly in the mediastinum, and some cases of renal and retroperitoneal involvement have been reported. However, Castleman disease that simultaneously involves the kidney and regional lymph nodes has not been reported in radiologic literature. We report a case of renal and pararenal Castleman disease, mimicking renal cell carcinoma with retroperitoneal lymphadenopathy.

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

    OpenAIRE

    Nozawa, Masahiro; Uemura, Hirotsugu

    2013-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

  16. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

    Science.gov (United States)

    Baine, Marina K.; Turcu, Gabriela; Zito, Christopher R.; Adeniran, Adebowale J.; Camp, Robert L.; Chen, Lieping

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. PMID:26317902

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

    Science.gov (United States)

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

    2014-02-01

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

  18. Significance of margin in nephron sparing surgery for renal cell carcinoma of 4 cm or less

    Institute of Scientific and Technical Information of China (English)

    LI Quan-lin; GUAN Hong-wei; WANG Fa-peng; JIANG Tao; WU Hong-chang; SONG Xi-shuang

    2008-01-01

    Background Current surgical practice for nephron sparing surgery allows at least 1 cm margin of normal tissue around the tumour.However,recent studies show that the width of the margin is not important.even simple enucleation is as effective as partial nephrectomy.We explored whether margin size has significant jmpacts on clinical outcomes in nephron sparing surgery for renal cell carcinoma of 4 cm or less.Methods Between 1998 and 2006,115 patients with sporadic,pathologically confirmed,renaI cell carcinoma 4 cm or Iass(T1a)and normal contralateral kidney were treated by nephron sparing surgery using a margin less than 5 mm.The surgical margin status was evaluated from frozen and permanent paraffin Sections.Results Mean and median tumour diameter were 3.3 cm and 3.5 cm(range 1.0-4.0).The mean margin width was 2.2 mm(median 2.0,range 0-6).In addition,114 cases had margins 5 mm or less(99.1%),97 cases(84.3%)had margin 3 mm or Iess,and 26 cases had margin zero(22.6%).None of the patients had positive surgical margins.No patients died during follow-up(mean 65 months).There were no any major surgical complications and no distant metastasis was detected.Local recurrence was detected in one case(0.9%)at a different site of the kidney.Conclusions For early Iocalized renaI cell carcinoma of 4 cm or Iess,as long as tumour is completely excised,the size of margin in nephron sparing surgery is not important.Nephron sparing surgery with 5 mm margin is enough for tumour control.It provides excellent renaI function preservation.favourable Iong term progression free survival and is not associated with an increased risk of Iocal recurrence.

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

    International Nuclear Information System (INIS)

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

  20. Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma

    OpenAIRE

    Eto, Masatoshi; Uemura, Hirotsugu; Tomita, Yoshihiko; Kanayama, Hiroomi; Shinohara, Nobuo; Kamei, Yoichi; Fujii, Yosuke; Umeyama, Yoshiko; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki; ,

    2014-01-01

    In an open-label, multicenter phase II study of Japanese patients with cytokine-refractory metastatic renal cell carcinoma, axitinib showed substantial antitumor activity with an acceptable safety profile. Here, we report overall survival and updated efficacy and safety results. Sixty-four Japanese patients with metastatic renal cell carcinoma following prior therapy with cytokines were treated with axitinib at a starting dose of 5 mg b.i.d. Following median treatment duration of 14.2 months,...

  1. Efficacy and Safety of Axitinib Versus Sorafenib in Metastatic Renal Cell Carcinoma: Subgroup Analysis of Japanese Patients from the Global Randomized Phase 3 AXIS Trial

    OpenAIRE

    Ueda, Takeshi; Uemura, Hirotsugu; Tomita, Yoshihiko; Tsukamoto, Taiji; Kanayama, Hiroomi; Shinohara, Nobuo; Tarazi, Jamal; Chen, Connie; Kim, Sinil; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki

    2013-01-01

    Objective Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated. Methods A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma. Results Twenty-five (of 361) and 29 (o...

  2. 18F-fluorodeoxyglucose positron emission tomography-computed tomography finding of left gonadal vein thrombosis in a case of renal cell carcinoma.

    Science.gov (United States)

    Narayan, Ravishwar; Ravishankar, Uma; Natarajan, Savita; Vohra, Sandeep

    2016-01-01

    Tumor thrombus from renal cell carcinoma is commonly reported in renal vein and inferior vena cava with a few reports of gonadal vein involvement. Here, we report a case of an elderly female who underwent fluorodeoxyglucose (FDG) positron emission tomography-computed tomography scan for initial staging of left renal cell carcinoma. Along with an FDG avid left renal mass lesion, scan also revealed FDG avid tumor thrombus in the entire length of the left gonadal vein.

  3. From aspecific to bispecific immunotherapy : immunomodulatory effects of interleukin-2 and T cell directed monoclonal antibodies in renal cell carcinoma patients

    NARCIS (Netherlands)

    Janssen, Richard Antonius Jozef

    1994-01-01

    The aim of this study was to get more insight into the immunological effects of rIL-2 therapy in renal cell carcinoma patients. Special attention was given to the activation of T cells, since these cells appear to play an important role in the immune response against tumour cells. In addition, the i

  4. Oxidative stress and apoptosis in intrinsic renal cell populations - an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Gobe, G.C.; Hogg, N.; Schoch, E.; James, M.; Willgoss, D.; Endre, Z. [University of Queensland, Brisbane, QLD (Australia)

    1996-12-31

    The authors have been studying the interaction between incidence of apoptosis and expression of selected oncogenes and cytokines in an in vivo rat model of ischaemia-reperfusion injury. The ischaemia itself, and the reperfusion, induce oxidative damage to the tissues, including damage from oxygen-derived free radicals. The scenario is therefore similar to radiation-induced injury. The proximal nephron segments, especially the pars recta, are usually acutely sensitive to ischaemia-reperfusion injury, undergoing necrosis in preference to apoptosis. A hypothesis was formed that Bcl-2 protection of the distal nephron, a segment of the nephron known as a reservoir for many growth factors or cytokines, allows increased production of growth factors during oxidative stress, which then act in a paracrine manner to protect the nearby proximal tubule. To test this hypothesis, an in vitro model of oxidative stress was used on either distal (Madin Derby Canine Kidney, MDCK) or proximal (human kidney-2, HK-2) established renal cell lines. We grow the cells as `coverslip cultures` in 12-well plates in Dulbecco`s Modified Eagle`s Medium or serum free medium. The treatments used are either hydrogen peroxide (a gradation of concentrations from 1mM to 50 mM), tumour necrosis factor-alpha (TNF-alpha) or hypoxia, as inducers of oxidative stress. The parameters analysed in the present study were (i) cell death (apoptosis or necrosis, using histology, in situ end labelling, and electron microscopy) (ii) cell proliferation and (iii) Bcl-2 expression (immunohistochemistry). It was found that all treatments increase levels of apoptosis in both cell lines, and TNF-alpha also causes increased cell proliferation. At the higher concentrations of hydrogen peroxide however, the HK-2 (proximal) cells have more of a tendency to undergo necrosis than do the MDCK (distal) cells, mimicking the in vivo situation. Bcl-2 expression is low in both cell lines, and does not appear to be affected by the

  5. Oxidative stress and apoptosis in intrinsic renal cell populations - an in vitro study

    International Nuclear Information System (INIS)

    The authors have been studying the interaction between incidence of apoptosis and expression of selected oncogenes and cytokines in an in vivo rat model of ischaemia-reperfusion injury. The ischaemia itself, and the reperfusion, induce oxidative damage to the tissues, including damage from oxygen-derived free radicals. The scenario is therefore similar to radiation-induced injury. The proximal nephron segments, especially the pars recta, are usually acutely sensitive to ischaemia-reperfusion injury, undergoing necrosis in preference to apoptosis. A hypothesis was formed that Bcl-2 protection of the distal nephron, a segment of the nephron known as a reservoir for many growth factors or cytokines, allows increased production of growth factors during oxidative stress, which then act in a paracrine manner to protect the nearby proximal tubule. To test this hypothesis, an in vitro model of oxidative stress was used on either distal (Madin Derby Canine Kidney, MDCK) or proximal (human kidney-2, HK-2) established renal cell lines. We grow the cells as 'coverslip cultures' in 12-well plates in Dulbecco's Modified Eagle's Medium or serum free medium. The treatments used are either hydrogen peroxide (a gradation of concentrations from 1mM to 50 mM), tumour necrosis factor-alpha (TNF-alpha) or hypoxia, as inducers of oxidative stress. The parameters analysed in the present study were (i) cell death (apoptosis or necrosis, using histology, in situ end labelling, and electron microscopy) (ii) cell proliferation and (iii) Bcl-2 expression (immunohistochemistry). It was found that all treatments increase levels of apoptosis in both cell lines, and TNF-alpha also causes increased cell proliferation. At the higher concentrations of hydrogen peroxide however, the HK-2 (proximal) cells have more of a tendency to undergo necrosis than do the MDCK (distal) cells, mimicking the in vivo situation. Bcl-2 expression is low in both cell lines, and does not appear to be affected by the

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

    Directory of Open Access Journals (Sweden)

    Todd M Gibson

    Full Text Available INTRODUCTION: Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. METHODS: Tag single nucleotide polymorphisms (SNPs selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS and the closely associated glutathione synthesis pathway (CTH, GGH, GSS were genotyped for 777 renal cell carcinoma (RCC cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163 with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. RESULTS: The strongest associations with RCC risk were observed for SLC19A1 (P(min-P = 0.03 and MTHFR (P(min-P = 0.13. A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785 was associated with a 37% increased risk (p = 0.02, and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. CONCLUSIONS: To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.

  7. Phase I trial of metastatic renal cell carcinoma with oral capecitabine and thalidomide

    Directory of Open Access Journals (Sweden)

    Brossart, Peter

    2009-06-01

    Full Text Available Background: The highly vascular nature of renal carcinoma cells suggests that inhibition of angiogenesis may be beneficial in this disease. Thalidomide has been described as inhibitor of the fibroblast growth factor (FGF and the vascular endothelial growth factor (VEGF. Therefore and in consideration of the promising response rates of the combination of IL-2, IFN-alpha and 5-FU [1] in metastatic renal cancer, we found it reasonable to test the combination of 5-FU and thalidomide. Thus, we conducted a phase I trial to determine safety, side effects and responses to such a treatment. Methods: Patients with metastasized renal cell cancer after nephrectomy and progress after IL-2 and interferon treatment, received oral 5-FU at a dose of 1250 mg/qm2 twice a day for two weeks, then after pausing a week, the oral application was restarted. In addition, oral thalidomide was applied constantly at a maximum dose of 400 mg/d. The combined therapy was given for three months. The primary endpoint was duration until disease progression, the secondary endpoint the response to treatment. Response was determined by CT scans three months after the end of treatment. Results: In total, 12 male patients participated in the trial and received the combined oral therapy. Concerning clinical response, one mixed response (8%, a stable disease in 4/12 patients (33% and progression was seen in 7 patients (58%. The survival from the start of the therapy showed a median of 21 months with three patients being alive. At present, the longest survival after the therapy is 51 months. Conclusions: The combination of oral 5-FU and thalidomide showed clinical response with tolerable side effects. Further studies will be required to assess the outcome of this treatment regimen.

  8. 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...

  9. Economic evaluation of temsirolimus on the basis of the results of the ARCC (Advanced Renal-Cell Carcinoma study

    Directory of Open Access Journals (Sweden)

    Simona de Portu

    2009-06-01

    Full Text Available Introduction: metastatic renal cell carcinoma (mRCC is highly resistant to chemotherapeutics, rendering limited antitumor effect. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. The Global ARCC Trial (Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma compared temsirolimus alone or temsirolimus plus interferon alfa with interferon alfa alone in mRCC. It has demonstrated that, as compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis while the addition of temsirolimus to interferon did not improve survival. Aim: the objective of our study was to investigate the pharmacoeconomic impact in the Italian context of temsirolimus vs interferon alfa in patients with metastatic renal-cell carcinoma and a poor prognosis. Methods: economic evaluation is based on clinical outcome data from the ARCC trial and was carried out conducting a cost/effectiveness analysis, comparing economic and clinical consequences of temsirolimus (25 mg weekly vs interferon alfa (18 MU 3 times weekly in the perspective of the Italian National Health Service. Direct medical costs included in the analysis were drug costs, costs associated with the management of treatment-related serious adverse events (grade 3 and 4, cost related to progression and best supportive care. Effects were measured in terms of overall survival. A sensitivity analysis was performed. Results: the cost of temsirolimus or interferon alfa therapy amounted to approximately € 14,000 and € 2,000 patient respectively. The cost of hospitalization related to drug toxicity was about € 1,500 for temsirolimus and € 2,100 for interferon alfa. Temsirolimus shows an incremental cost per patient per month saved of € 3,767. Sensitivity analysis demonstrates that cost consequences parameters are sensitive to fluctuation. Discussion

  10. 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.

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

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    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.

  12. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Efficacy and safety of axitinib in elderly patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Miyake, Hideaki; Harada, Ken-Ichi; Ozono, Seiichiro; Fujisawa, Masato

    2016-08-01

    The objective of this study was to analyze the impact of age on clinical outcomes of metastatic renal cell carcinoma (mRCC) patients receiving axitinib. This study included 144 consecutive mRCC patients who received axitinib for at least 12 weeks as second-line therapy in a routine clinical setting. The efficacy, safety and quality of life (QOL) were compared between patients aged <75 (n = 116) and ≥75 (n = 28) years. No significant differences in the clinicopathological characteristics were noted between younger and older patients. There was no significant difference in the response rate, clinical benefit rate or proportion of patients going on to receive third-line therapy between these two groups. In addition, the progression-free and overall survivals in older patients were similar to those in younger patients. There were no significant differences in the incidences of adverse events between these two groups, except for that of fatigue, which was significantly more frequent in older than younger patients. There was no significant difference in the incidence of the discontinuation of axitinib due to adverse events between the two groups. QOL assessment at 12 weeks after the introduction of axitinib using the Medical Outcomes Study 36-Item Short Form showed no significant differences in any of the eight scale scores between the two groups. Taken together, it might be possible to achieve clinical outcomes in older patients receiving axitinib comparable to those in younger patients, suggesting that advanced age should not be a contraindication to treatment with axitinib as a second-line setting in mRCC patients. PMID:27444960

  15. Expression of CD44 and P53 in renal cell carcinoma: Association with tumor subtypes

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    Farahnaz Noroozinia

    2014-01-01

    Full Text Available Renal cell carcinoma (RCC is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3% specimens were P53 positive, 30/64 (46.9% were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5. A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5 and age (P = 0.07, sex (P= 0.3, tumor size (P = 0.7, grade (P = 0.23, vascular invasion (P = 1.00 and ureteral invasion (P = 1.00. Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3, sex (P = 0.7, tumor size (P = 0.7, grade (P = 0.1, vascular inva-sion (P = 1.00 and ureteral invasion (P = 1.00. According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.

  16. Renal cell cancer: a shift in approaches for treatment of advanced disease in the United States.

    Science.gov (United States)

    Banegas, Matthew P; Harlan, Linda C; Mann, Bhupinder; Yabroff, K Robin

    2014-09-01

    Several new agents have become available to treat renal cell cancer (RCC) in recent years, although evidence on their dissemination is limited. This study examined recent trends in RCC treatment in US community practices. Data from the population-based National Cancer Institute's Patterns of Care studies were used to evaluate treatment of patients with RCC newly diagnosed in 2004 and 2009 (N=2357). Descriptive statistics and logistic and Cox proportional hazards regression analyses were used to assess treatment patterns and the associations among demographic, clinical, and hospital characteristics, with receipt of systemic therapy and time-to-systemic treatment. Between 2004 and 2009, systemic therapy use increased among patients with stage III and IV RCC, from 3.8% to 15.7% and 35.2% to 57.4%, respectively. Among patients with stage IV disease, the most commonly used therapies changed from interleukin-2 (16.3%) and interferon-alfa (16.6%) in 2004 to sunitinib (39.2%) and temsirolimus (15.2%) in 2009. Further, notable decreases were seen in the use of surgery and time-to-systemic treatment for patients with stage IV disease. Patients who were older, living in areas with lower educational attainment, and diagnosed in 2004 were significantly less likely to receive systemic therapy and had longer time-to-systemic treatment (P<.05). The findings indicate that over the past decade, treatment for RCC in the United States has evolved toward increased use of systemic therapy. As the diffusion of new therapies continues, it will be imperative to understand how variation in care for RCC will impact health outcomes and costs of care. PMID:25190695

  17. Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

    Directory of Open Access Journals (Sweden)

    Brian W. Cross

    2012-01-01

    Full Text Available Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR and overall survival in localized renal cell carcinoma (RCC following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr, intermediate (20.1–50.0 mm/hr, and high risk (>50.0 mm/hr groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI survival was 44.1 (42.6–45.5 months, 35.5 (32.3–38.8 months, and 32.1 (25.5–38.6 months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649 and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228 increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC.

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

    Directory of Open Access Journals (Sweden)

    Mahadevia Parthiv J

    2007-06-01

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

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

    Science.gov (United States)

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

    2005-11-20

    Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that includes 150-item food-frequency questions and additional questions on lifestyle factors, at baseline in 1986. A case-cohort approach was used. After 9.3 years of follow-up, 275 microscopically confirmed incident cases were identified. Subjects with incomplete or inconsistent dietary data were excluded, leaving 260 RCC cases for analyses on fruit consumption and 249 RCC cases for analyses on vegetable consumption. Incidence rate ratios (RR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RRs for exposure variables are expressed per increment of 25 g/day and are adjusted for age, sex, smoking, body mass index and history of hypertension at baseline. The RRs for vegetable consumption were further adjusted for fruit consumption and vice versa. Total vegetable and fruit consumption (RR: 1.00; 95% CI 0.97-1.02), vegetable (RR: 1.00, 95% CI 0.96-1.06) and fruit consumption (RR: 1.00; 95% CI 0.97-1.03) were not associated with RCC risk. Also, no association existed for botanical subgroups of vegetables and fruit. For 30 individual vegetables and fruits, we observed one that significantly increased RR (mandarin consumption, RR: 1.76; 95% CI 1.28-2.42), which must be regarded cautiously because of multiple testing. These results suggest the absence of an association between vegetable and/or fruit consumption and RCC risk.

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

    Science.gov (United States)

    Yang, Y-Q; Chen, J

    2014-01-01

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

  1. MRI-guided percutaneous laser ablation of small renal cell carcinoma: Initial clinical experience

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    Kariniemi, Juho; Ojala, Risto; Hellstroem, Pekka; Sequeiros, Roberto Blanco (Dept. of Radiology, Dept. of Surgery, Oulu Univ. Hospital, Oulu (Finland)), e-mail: juho.kariniemi@oulu.fi

    2010-05-15

    Background: The number of detected small renal cell carcinomas (RCCs) has been rising, largely due to advances in imaging. Open surgical resection is the standard management of small RCCs; however, imaging-guided percutaneous ablative therapies have emerged as a minimally invasive treatment alternative, especially for patients who are poor candidates for surgery. Purpose: To evaluate the initial clinical experience of magnetic resonance imaging (MRI)-guided percutaneous laser ablation of small RCCs. Material and Methods: Eight patients with 10 tumors were treated with percutaneous MRI-guided laser ablation. All tumors (diameter range 1.5-3.8 cm, mean 2.7 cm) were biopsy-proven RCCs. By using a 0.23 T open MRI system and general anesthesia in patients, one to four (mean 2.6) laser fibers were placed and the tumors were ablated under near real-time MRI control by observing the signal void caused by the temperature change in the heated tissue. The treatment was considered successful if the tumor showed no contrast enhancement at follow-up imaging. Results: All except one tumor were successfully ablated in one session. The first patient treated showed enhancing residual tumor in post-procedural MRI; she has thus far declined retreatment. One complication, a myocardial infarction, occurred; all other patients tolerated the procedure well. No local recurrence was discovered during the follow-up (range 12-30 months, mean 20 months). Conclusion: In this small group of patients with relatively short follow-up period, MRI-guided percutaneous laser ablation proved to be a promising treatment option for small RCCs

  2. Detection of renal cell carcinoma using neutron time of flight spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Viana, Rodrigo S.; Yoriyaz, Helio, E-mail: rodrigossviana@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Lakshmanan, Manu N.; Agasthya, Greeshma A.; Kapadia, Anuj J. [Duke University Medical Center, Durham, NC, (United States). Ravin Advanced Imaging Labs, Radiology

    2013-07-01

    The diagnosis of renal cell carcinoma (RCC) is challenging because the symptoms accompanying it are not unique to the disease, and can therefore be misdiagnosed as other diseases. Due to this characteristic, detection of renal cancer is incidental most of time, occurring via abdominal radiographic examinations unrelated to the disease. Presently, biopsy, which is invasive and an unpleasant procedure for the patient, is the most commonly used technique to diagnose RCC. In this study, we demonstrate the application of a novel noninvasive technique for detecting and imaging RCC in vivo. The elemental composition of biological tissues including kidneys has been investigated using a new technique called Neutron Stimulated Emission Computed Tomography (NSECT). This technique is based on detecting the energy signature emitted by the stable isotopes of elements in the body, which are stimulated to emit gamma radiation via inelastic neutron scattering. Methods for improving detection sensitivity and reducing dose, such as time-of-flight neutron spectroscopy have been explored. MCNP5 simulations were used to model the NSECT scanning of the human kidney where the energy and time of arrival of gamma photons were recorded in an ideal detector placed around the human torso. A 5 MeV collimated neutron beam was used to irradiate the kidney containing an RCC lesion. The resulting spectra were resolved in 100 picosecond and 1 keV time and energy bins, respectively. The preliminary results demonstrate the ability to localize the lesion through neutron time of flight spectroscopy and generate a tomographic image at a low dose to the patient. (author)

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

    Science.gov (United States)

    Bukowski, Ronald M

    2011-01-01

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

  4. Intraoperative EBRT and resection for renal cell carcinoma. Twenty-year outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.A. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Sole, C.V. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Instituto de Radiomedicina, Santiago (Spain). Service of Radiation Oncology; Martinez-Monge, R.; Aristu, J. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Radiation Oncology; Azinovic, I. [Hospital de San Jaime, Torrevieja (Spain). Dept. of Radiation Oncology; Zudaire, J.; Berian, J.M. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Urology; Garcia-Sabrido, J.L. [Hospital General Universitario Gregorio Maranon, Madrid (Spain). Dept. of General Surgery

    2013-02-15

    Purpose: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Patients and methods: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. Conclusion: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation. (orig.)

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

    Science.gov (United States)

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

    2016-02-01

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

  6. Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients

    International Nuclear Information System (INIS)

    To evaluate the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. The CRP-level, stratified to three subgroups (CRP ≤ 4, 4–10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4–10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP ≤4 mg/l, respectively. A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients

  7. Fibre intake and renal cell carcinoma: a case-control study from Italy.

    Science.gov (United States)

    Galeone, Carlotta; Pelucchi, Claudio; Talamini, Renato; Negri, Eva; Montella, Maurizio; Ramazzotti, Valerio; Zucchetto, Antonella; Dal Maso, Luigino; Franceschi, Silvia; La Vecchia, Carlo

    2007-10-15

    Only 2 previous studies, conducted in Australia, United States and northern Europe, considered the role of dietary fibre intake on renal cell carcinoma (RCC) risk, and both showed a modest, inverse association. Therefore, we investigated in depth the topic of fibres and RCC, using data from a multicenter case-control study conducted in Italy from 1992 to 2004, including 767 cases with incident, histologically confirmed RCC and 1,534 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. The continuous OR for an increase in intake equal to the difference between the 80th and the 20th percentile were 0.94 (95% CI: 0.82-1.08) for total dietary fibre, 0.98 (95% CI: 0.85-1.13) for soluble noncellulose polysaccharides, 0.92 (95% CI: 0.80-1.05) for total insoluble fibre, 0.90 (95% CI: 0.78-1.04) for cellulose, 0.95 (95% CI: 0.84-1.06) for insoluble noncellulose polysaccharides and 1.06 (95% CI: 0.93-1.21) for lignin. With reference to the sources of fibre, we found an inverse association with vegetable fibre (OR = 0.84, 95% CI: 0.73-0.97), but no association with fruit (OR = 0.98, 95% CI: 0.86-1.12) and grain fibre (OR = 1.05, 95% CI: 0.95-1.15). The inverse association with vegetable fibre may reflect a real favorable effect, or be an indicator of a beneficial role of a diet rich in vegetable on RCC risk. PMID:17582601

  8. Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma.

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    Vivekanand Gupta

    Full Text Available The role that stromal renal cell carcinoma (RCC plays in support of tumor progression is unclear. Here we sought to determine the predictive value on patient survival of several markers of stromal activation and the feasibility of a fibroblast-derived extracellular matrix (ECM based three-dimensional (3D culture stemming from clinical specimens to recapitulate stromal behavior in vitro. The clinical relevance of selected stromal markers was assessed using a well annotated tumor microarray where stromal-marker levels of expression were evaluated and compared to patient outcomes. Also, an in vitro 3D system derived from fibroblasts harvested from patient matched normal kidney, primary RCC and metastatic tumors was employed to evaluate levels and localizations of known stromal markers such as the actin binding proteins palladin, alpha-smooth muscle actin (α-SMA, fibronectin and its spliced form EDA. Results suggested that RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis, as demonstrated by overall survival time. Conversely, cases of RCCs where stroma presents low levels of palladin expression indicate increased survival times and, hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the categorization of stromal RCCs into discrete progressive stromal stages, also show increased levels of expression and stress fiber localization of α-SMA and palladin, as well as topographical organization of fibronectin and its splice variant EDA. These observations are concordant with expression levels of these markers in vivo. The study proposes that palladin constitutes a useful marker of poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately represent the specific patient's tumor-associated stromal compartment. Our observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC

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

    Science.gov (United States)

    Liu, Yiyan

    2016-01-01

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

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

    Science.gov (United States)

    Liu, Yiyan

    2016-01-01

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

  11. Outcome and Safety of Sorafenib in Metastatic Renal Cell Carcinoma Dialysis Patients: A Systematic Review.

    Science.gov (United States)

    Leonetti, Alessandro; Bersanelli, Melissa; Castagneto, Bruno; Masini, Cristina; Di Meglio, Giovanni; Pellegrino, Benedetta; Buti, Sebastiano

    2016-08-01

    Few data are available about sorafenib use in patients with metastatic renal cell carcinoma (mRCC) undergoing hemodialysis. No systematic review has been previously performed about this issue. The objective of the present review is to investigate pharmacokinetics and clinical outcomes of sorafenib in mRCC patients undergoing hemodialysis. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all the literature about mRCC dialysis patients receiving sorafenib, published from January 1946 to August 2015, was evaluated. Applying inclusion/exclusion criteria, 11 articles were selected for the analysis; 1 patient from our department was also included. The investigated outcomes were pharmacokinetics, toxicity, response rate, progression-free survival, and overall survival where available. A total of 36 patients were included. Median treatment duration was 6.0 months on overall population; median progression-free survival was 6.3 months (calculated on 19 patients); response rate was 22% (on 29 patients); median overall survival was 14.9 months (on 28 patients). Of note, 24 patients started sorafenib at reduced dose; 6 of 36 patients (17%) required dose reduction due to adverse events (AEs). Sorafenib treatment was discontinued in 7 patients (19%) because of AEs. Most of AEs were Grade 1-2; severe toxicities (Grade 4-5) included G4 anemia (1 case), G4 hypertension (1 case), G4 cerebellar hemorrhage (1 patient), and a case of G5 subarachnoid hemorrhage. This review confirmed the efficacy of sorafenib treatment in mRCC patients receiving hemodialysis. Nevertheless, drug toxicity seems to be increased in these patients, despite the initiation of therapy at reduced doses; therefore, sorafenib should be used with caution in dialysis patients. PMID:26899142

  12. Lingual metastasis from renal cell carcinoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2012-06-01

    Full Text Available Renal cell carcinoma (RCC accounts for the 3% of all solid tumors. Despite continuous improvement in the therapy regimen, less has been achieved in terms of enabling an earlier diagnosis: the neoplasia usually reveals its presence at an advanced stage, obviously affecting prognosis. The most frequent sites of secondary disease are shown to be lungs (50-60%, bone (30-40%, liver (30-40% and brain (5%; while the head and neck district seems to account for less than 1% of patients with primary kidney lesion. We report here the case of a 70-year old man who presented with acute renal failure due to abdominal recurrence of RCC 18 years post nephrectomy. After a few months of follow up without any systemic therapy due to the renal impairment, the patient presented a vascularized tongue lesion that was demonstrated to be a secondary localization of the RCC. This lesion has, therefore, been treated with microsphere embolization to stop the frequent bleeding and to lessen the unbearable concomitant symptoms it caused, such as dysphagia and pain. A tongue lesion that appears in a RCC patient should always be considered suspect and a multidisciplinary study should be conducted both to assess whether it is a metastasis or a primary new lesion and to understand which method should be selected, if necessary, to treat it (surgery, radiation or embolization. Lingual metastasis should be examined accurately not only because they seem to implicate a poor prognosis, but also because they carry a burden of symptoms that not only threatens patients’ lives but also has a strong impact on their quality of life.

  13. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

    Science.gov (United States)

    Suarez, Eloah Rabello; Chang, De-Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J.; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A.

    2016-01-01

    Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. PMID:27145284

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

    Directory of Open Access Journals (Sweden)

    Ghadeer A Mokhtar

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Renal cells express different forms of vimentin: the independent expression alteration of these forms is important in cell resistance to osmotic str