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Sample records for 786-o renal cell

  1. Nrdp1-mediated degradation of BRUCE decreases cell viability and induces apoptosis in human 786-O renal cell carcinoma cells

    PubMed Central

    Chen, Shao-Jun; Lin, Jian-Hai; Yao, Xu-Dong; Peng, Bo; Xu, Yun-Fei; Liu, Min; Zheng, Jun-Hua

    2016-01-01

    Neuregulin receptor degradation protein-1 (Nrdp1) is involved in a plethora of cellular processes and plays an essential role in the development and progression of human cancers. However, its role in renal cell carcinoma (RCC) remains unclear. Therefore, the present study aimed to explore the biological significance of Nrdp1 in RCC. Western blot analyses of tissue samples from 24 patients with primary RCC revealed lower Nrdp1 and higher baculovirus inhibitor of apoptosis repeat-containing ubiquitin-conjugating enzyme (BRUCE) protein levels in RCC tissues compared with adjacent normal tissues. In addition, MTT and apoptosis assays demonstrated that Nrdp1 overexpression resulted in decreased cell viability and enhanced apoptosis in RCC 786-O cells; conversely, Nrdp1 knockdown increased 786-O cell viability and inhibited apoptosis. Further analysis showed that BRUCE downregulation partially attenuated the effects of Nrdp1 knockdown on RCC cell viability and apoptosis. Moreover, an inverse association was obtained between BRUCE and Nrdp1 protein levels. These findings suggest that Nrdp1-mediated degradation of BRUCE decreases cell viability and induces apoptosis in RCC cells, highlighting Nrdp1 as a potential target for RCC treatment.

  2. Hyperthermia Induces Apoptosis of 786-O Cells through Suppressing Ku80 Expression

    PubMed Central

    Qi, Defeng; Hu, Yuan; Li, Jinhui; Peng, Tao; Su, Jialin; He, Yun; Ji, Weidong

    2015-01-01

    Hyperthermia as an anticancer method has been paid increasing attention in recent years. Several studies have shown that hyperthermia can kill tumor cells by inducing apoptosis. However, the underlying molecular mechanisms of hyperthermia-induced apoptosis are largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis in renal carcinoma 786-O cells, we firstly examined apoptosis and Ku expression in 786-O cell line treated with heat exposure (42°C for 0-4 h). The results showed that hyperthermia induced apoptosis of 786-O cells, and suppressed significantly Ku80 expression, but not Ku70 expression. Next, we knock-down Ku80 in 786-O cells, generating stable cell line 786-O-shKu80, and detected apoptosis, cell survival and cell cycle distribution. Our data showed higher apoptotic rate and lower surviving fraction in the stable cell line 786-O-shKu80 compared with those in control cells, exposed to the same heat stress (42°C for 0-4 h). Moreover, the results also showed suppression of Ku80 led to G2/M phase arrest in the stable cell line 786-O-shKu80 following heat treatment. Together, these findings indicate that Ku80 may play an important role in hyperthermia-induced apoptosis and heat-sensitivity of renal carcinoma cells through influencing the cell cycle distribution. PMID:25902193

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

    PubMed Central

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

    2016-01-01

    Renal cell carcinoma (RCC) is one of the common tumors in the urinary system without effective therapies. Angiomotin (Amot) can interact with Yes-associated protein (YAP) to either stimulate or inhibit YAP activity, playing a potential role in cell proliferation. However, the role of Amot in regulating the proliferation of renal epithelial and RCC cells is unknown. Here, we show that Amot is expressed predominantly in the nucleus of RCC cells and tissues, and in the cytoplasm and nucleus of renal epithelial cells and paracancerous tissues. Furthermore, Amot silencing inhibited proliferation of HK-2 and 786-O cells while Amot upregulation promoted proliferation of ACHN cells. Interestingly, the location of Amot and YAP in RCC clinical samples and cells was similar. Amot interacted with YAP in HK-2 and 786-O cells, particularly in the nucleus. Moreover, Amot silencing mitigated the levels of nuclear YAP in HK-2 and 786-O cells and reduced YAP-related CTGF and Cyr61 expression in 786-O cells. Amot upregulation slightly increased the nuclear YAP and YAP-related gene expression in ACHN cells. Finally, enhanced YAP expression restored proliferation of Amot-silencing 786-O cells. Together, these data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation. PMID:26848622

  4. Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma.

    PubMed

    Lai, Cai-Yong; Xu, Yin; Yu, Gan-Shen; Wu, Xun; Li, Yun-Fei; Pan, Bin; Heng, Bao-Li; Xue, Yi-Jun; Su, Ze-Xuan

    2016-06-01

    Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells. PMID:26948025

  5. miR-630 functions as a tumor oncogene in renal cell carcinoma

    PubMed Central

    Zhao, Jian-Jun; Chen, Peng-Jie; Duan, Rui-Qin; Li, Ke-Ji; Wang, Yu-Zhong

    2016-01-01

    Introduction MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cell processes during cancer progression. Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. In this study, we aimed to investigate the roles of miR-630 in RCC progression. Material and methods Expression of miR-630 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in four renal cancer cell lines (786-O, ACHN, Caki-1, and Caki-2) and one normal human proximal tubule epithelial cell line (HK-2). Next, miR-630 inhibitor was used to inhibit miR-630 expression in 786-O cells. Finally, its effects on cell proliferation, apoptosis, migration, and invasion were evaluated. Results The expression level of miR-630 was higher in renal cancer cell lines 786-O, ACHN, Caki-1, and Caki-2 than that in the normal renal cell line HK-2 (p < 0.05). Furthermore, a proliferation assay, apoptosis assay, migration assay and invasion assay were performed, and the results showed that down-regulation of miR-630 expression by miR-630 inhibitor significantly inhibited cell proliferation, migration, and invasion, which meanwhile induced cell apoptosis of the renal cancer cell line 786-O. Conclusions This is the first time that miR-630 expression has been shown to be associated with renal cancer progression, and down-regulation of miR-630 can inhibit tumor progression, which provides a potential therapeutic target for renal cancer treatment. PMID:27279836

  6. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

    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

  7. Induction of cell cycle arrest, DNA damage, and apoptosis by nimbolide in human renal cell carcinoma cells.

    PubMed

    Hsieh, Yi-Hsien; Lee, Chien-Hsing; Chen, Hsiao-Yun; Hsieh, Shu-Ching; Lin, Chia-Liang; Tsai, Jen-Pi

    2015-09-01

    Nimbolide is a tetranortriterpenoid isolated from the leaves and flowers of Azadirachta indica which has been shown to exhibit anticancer, antioxidant, anti-inflammatory, and anti-invasive properties in a variety of cancer cells. However, the anti-tumor effect on human renal cell carcinoma (RCC) cells is unknown. In this study, we found that nimbolide treatment had a cytotoxic effect on 786-O and A-498 RCC cells in a dose-dependent manner. According to flow cytometric analysis, nimbolide treatment resulted in G2/M arrest in 786-O and A-498 cells accompanied with an increase in the phosphorylation status of p53, cdc2, cdc25c, and decreased expressions of cyclin A, cyclin B, cdc2, and cdc25c. Nimbolide also caused DNA damage in a dose-dependent manner as determined by comet assay and measurement of γ-H2AX. In addition, apoptotic cells were observed in an Annexin V-FITC/propidium iodide double-stained assay. The activities of caspase-3, -9, and poly ADP-ribose polymerase (PARP) were increased, and the expression of pro-caspase-8 was decreased in nimbolide-treated 786-O and A-498 cells. Western blot analysis revealed that the levels of intrinsic-related apoptotic proteins Bax and extrinsic-related proteins (DR5, CHOP) were significantly increased in nimbolide-treated 786-O and A-498 cells. In addition, the expressions of Bcl-2 and Mcl-1 were decreased in 786-O and A-498 cells after nimbolide treatment. We conclude that nimbolide can inhibit the growth of human RCC cells by inducing G2/M phase arrest by modulating cell cycle-related proteins and cell apoptosis by regulating intrinsic and extrinsic caspase signaling pathways. Nimbolide may be a promising therapeutic strategy for the treatment of RCC. PMID:25916210

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy.

    PubMed

    Yamasaki, Toshinari; Kamba, Tomomi; Kanno, Toru; Inoue, Takahiro; Shibasaki, Noboru; Arakaki, Ryuichiro; Yamada, Tomomi; Kondo, Keiichi; Kamoto, Toshiyuki; Nishiyama, Hiroyuki; Ogawa, Osamu; Nakamura, Eijiro

    2012-11-01

    Vascular endothelial growth factor (VEGF)-targeted therapies show significant antitumor effects for advanced clear cell renal cell carcinomas (CC-RCCs). Previous studies using VEGF inhibitors in mice models revealed that VEGF-dependent capillaries were characterized by the existence of endothelial fenestrations (EFs). In this study, we revealed that capillaries with abundant EFs did exist, particularly in CC-RCCs harboring VHL mutation. This finding was recapitulated in mice xenograft models, in which tumors from VHL null cells showed more abundant EFs compared to those from VHL wild-type cells. Importantly, treatment with bevacizumab resulted in a significant decrease of tumor size established from VHL null cells. Additionally, a significant reduction of EFs and microvessel density was observed in VHL null tumors. Indeed, xenograft from 786-O/mock (pRC3) cells developed four times more abundant EFs than that from 786-O/VHL (WT8). However, introduction of the constitutively active form of hypoxia-inducible factor (HIF)-2α to WT8 cells failed to either augment the number of EFs or restore the sensitivity to bevacizumab in mice xenograft, irrespective of the equivalent production of VEGF to 786-O/mock cells. These results indicated that HIF-2α independent factors also play significant roles in the development of abundant EFs. In fact, several angiogenesis-related genes including CCL2 were upregulated in 786-O cells in a HIF-2α independent manner. Treatment with CCL2 neutralizing antibody caused significant reduction of capillaries with EFs in 786-O xenograft, indicating that they were also sensitive to CCL2 inhibition as well as VEGF. Collectively, these results strongly indicated that capillaries with distinctive phenotype developed in VHL null CC-RCCs are potent targets for anti-angiogenic therapy. PMID:22931246

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

    PubMed

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

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P < 0.05). As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene. PMID:25419360

  11. CCN3 (NOV) regulates proliferation, adhesion, migration and invasion in clear cell renal cell carcinoma

    PubMed Central

    LIU, SHUAI; LIU, ZHENG; BI, DONGBIN; YUAN, XAODONG; LIU, XIAOWEN; DING, SENTAI; LU, JIAJU; NIU, ZHIHONG

    2012-01-01

    The CCN3/nephroblastoma overexpressed gene belongs to the CCN family of genes that encode secreted proteins involved in a variety of processes including tumorigenesis. Altered expression of CCN3 has been observed in human nephroblastoma and renal cell carcinoma (RCC), suggesting that CCN3 plays a role in kidney tumorigenesis. The aim of the present study was to examine the role of CCN3 in clear cell RCC biology. In particular, we studied the expression of CCN3 in 32 pairs of RCC tissues and corresponding normal kidney tissues using immunohistochemistry. The CCN3 gene was transfected into the 786-O cell line and the behaviors of stably transfected clones were analyzed. Results showed the expression of CCN3 was lower in RCC tissues compared to corresponding normal kidney tissues and the expression of CCN3 was inversely correlated with the Ki67 index. CCN3-expressing clones exhibited significantly inhibited cell proliferation. Furthermore, CCN3-transfected 786-O cells exhibited increased adhesion to extracellular matrix proteins, migration and invasion in Matrigel. Our data indicated that CCN3 plays an anti-proliferative role in clear cell RCC cells and promotes the adhesion, migration and invasion of clear cell RCC cells. PMID:22783399

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

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

  17. [Hereditary renal cell carcinomas].

    PubMed

    Hartmann, A; Stöhr, C G; Junker, K

    2010-10-01

    Renal cell carcinomas occur in several hereditary tumor syndromes. These renal tumors frequently have a specific histopathological appearance which can be a sign for a hereditary cause of the disease. The genetic alterations responsible for most of these tumor syndromes were identified in recent years. Interestingly, renal cell carcinomas show specific histopathological features in each of the hereditary renal cancer syndromes. Clear cell and often cystic renal cell carcinomas occur in von Hippel-Lindau syndrome (VHL), while oncocytomas and chromophobe renal cell carcinomas are found in the Birt-Hugg-Dube syndrome, often also as hybrid tumors. Well differentiated papillary carcinomas (Type 1 according to the WHO) are found in the hereditary papillary renal cell carcinoma (HPRC). In contrast, poorly diffentiated papillary renal cell carcinomas (Type 2 according to the WHO) occur in combination with leiomyomas and leiomyosarcomas of the skin and uterus in hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The various genetic causes for these hereditary tumor syndromes open up new therapeutic possibilities, some of which are already being investigated in clinical studies. PMID:20960197

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

    SciTech Connect

    Meng, Fandong; Li, Yan; Tian, Xin; Fu, Liye; Yin, Yuanqin; Sui, Chengguang; Ma, Ping; Jiang, Youhong

    2014-10-10

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

  19. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

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

  20. KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma.

    PubMed

    Guo, Zhongqiang; Liu, Jin; Zhang, Lian; Su, Boxing; Xing, Yunchao; He, Qun; Ci, Weimin; Li, Xuesong; Zhou, Liqun

    2015-02-01

    Potassium inwardly rectifying channel, subfamily J, member 1 (KCNJ1), as an ATP-dependent potassium channel, plays an essential role in potassium balance. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. Here, we studied the expression and function of KCNJ1 in ccRCC. The expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. p3xFLAG-CMV-14 vector containing KCNJ1 was constructed and used for transfecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion, and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay, and flow cytometry, respectively. We found that KCNJ1 was low-expressed in ccRCC tissues samples and cell lines, and its expression level was significantly associated with tumor pathology grade (P = 0.002) and clinical stage (P = 0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient's survival (P = 0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion and promoted cancer cell apoptosis. Moreover, knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis. PMID:25344677

  1. AB179. KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma

    PubMed Central

    Guo, Zhongqiang; Liu, Jin; Su, Boxing; Li, Xuesong; Zhou, Liqun

    2014-01-01

    Objective Potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), plays an essential role in potassium balance by transporting potassium out of cells. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. The aim of this study was to detect the expression of KCNJ1 in ccRCC and determine the relationship of KCNJ1 expression with the progression and prognosis of ccRCC. Methods Expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by qRT-PCR, Western blot and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. P3xFLAG-CMV-14 vector containing KCNJ1 was constructed, and used for infecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay and flow cytometry. Results KCNJ1 was low-expressed in ccRCC tissues samples and cell lines. The KCNJ1 expression level was significantly associated with tumor pathology grade (P=0.002), and clinical stage (P=0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient’s survival (P=0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion, and promoted cancer cell apoptosis. Conclusions Taken together, we concluded that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis.

  2. Radiosensitization by Inhibiting STAT1 in Renal Cell Carcinoma

    SciTech Connect

    Hui Zhouguang; Tretiakova, Maria; Zhang Zhongfa; Li Yan; Wang Xiaozhen; Zhu, Julie Xiaohong; Gao Yuanhong; Mai Weiyuan; Furge, Kyle; Qian Chaonan; Amato, Robert; Butler, E. Brian

    2009-01-01

    Purpose: Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. Methods and Materials: The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. Results: STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10{sup -8} for clear cell; and p = 3.6 x 10{sup -4} for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. Conclusion: This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.

  3. Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma.

    PubMed

    Nagata, Masayoshi; Sakurai-Yageta, Mika; Yamada, Daisuke; Goto, Akiteru; Ito, Akihiko; Fukuhara, Hiroshi; Kume, Haruki; Morikawa, Teppei; Fukayama, Masashi; Homma, Yukio; Murakami, Yoshinori

    2012-03-15

    Renal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin-binding protein, 4.1B/DAL-1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin-superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM-family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786-O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B. PMID:21544807

  4. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  5. miR-155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2

    PubMed Central

    Li, Hongzhao; Fan, Yang; Zhang, Yu; Zhao, Chaofei; Wang, Lei; Ma, Minghui; Lei, Zhengwei; Zhang, Xu

    2016-01-01

    MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC. PMID:26967247

  6. MicroRNA-27a functions as a tumor suppressor in renal cell carcinoma by targeting epidermal growth factor receptor

    PubMed Central

    LI, YUEYAN; LI, JIE; SUN, XIAOLEI; CHEN, JIACUN; SUN, XIAOQING; ZHENG, JUNNIAN; CHEN, RENFU

    2016-01-01

    Numerous studies have suggested that microRNAs (miRNAs) are vital in the development of various types of human cancers, including renal cell carcinoma (RCC), and the regulation of tumor progression and invasion. However, the effect of miRNA-27a (miR-27a) on the tumorigenesis of RCC is unclear. The aim of the present study was to investigate the function of miR-27a and identify its possible target genes in RCC cells. In the present study, cell proliferation, migration and invasion and the percentage of apoptotic cells were detected by methylthiazol tetrazolium assays, Annexin V analysis, wound-healing assays and Transwell invasion assays. Western blot analysis was performed to validate the protein expression level and assess whether the epidermal growth factor receptor (EGFR) was a target gene of miR-27a. A tumor xenograft animal model was used to detect the role of miR-27a on RCC cell growth in vivo. The present study demonstrated that miR-27a significantly suppressed human RCC 786-O cell proliferation and induced cell apoptosis. Restoration of miR-27 also resulted in 786-O cell migration and invasion inhibition. Furthermore, upregulated miR-27a attenuated RCC tumor growth in the tumor xenograft animal model. The present results suggested that miR-27a functions as a tumor suppressor in RCC. The western blot analysis assay revealed that EGFR was a novel target of miR-27a. The growth suppression of RCC cells was attributed partly to the downregulation of the cell cycle by ERFR inhibition. The present findings may aid in the understanding of the molecular mechanism of miR-27a in the tumorigenesis of RCC, and may provide novel diagnostic and therapeutic options for RCC. PMID:27313769

  7. KIAA0101 is associated with human renal cell carcinoma proliferation and migration induced by erythropoietin

    PubMed Central

    Fan, Shengjun; Li, Xin; Tie, Lu; Pan, Yan; Li, Xuejun

    2016-01-01

    Erythropoietin (EPO) is a frequently prescribed anti-anemic drug for patients with advanced renal carcinoma. However, recent evidence from clinical studies suggested that EPO accelerated tumor progression and jeopardized the 5-year survival. Herein, we show, starting from the in silico microarray bioinformatics analysis, that activation of Erythropoietin signaling pathway enhanced renal clear carcinoma (RCC) progression. EPO accelerated the proliferative and migratory ability in 786-O and Caki-2 cells. Moreover, comparative proteomics expression profiling suggested that exogenous EPO stimulated RCC progression via up-regulation of KIAA0101 expression. Loss of KIAA0101 impeded the undesirable propensity of EPO in RCC. Finally, low expression of KIAA0101 was associated with the excellent prognosis and prognosticated a higher 5-year survival in human patients with renal carcinoma. Overall, KIAA0101 appears to be a key promoter of RCC malignancy induced by EPO, which provide mechanistic insights into KIAA0101 functions, and pave the road to develop new therapeutics for treatment of cancer-related and chemotherapy-induced anemia in patients with RCC. PMID:26575329

  8. Renal cell carcinoma

    PubMed Central

    Gao, Jianjun; Rathmell, W Kimryn

    2014-01-01

    The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC. PMID:25385470

  9. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  10. Radiographic Kinetics of Sarcomatoid Renal Cell Carcinoma.

    PubMed

    Syed, Ali; Raval, Amar; Pridjian, Andrew; Birbe, Ruth; Trabulsi, Edouard J

    2016-07-01

    Renal cell carcinoma is a common entity often managed surgically with excellent survival benefits. We report a rare case of sarcomatoid renal cell carcinoma with aggressive growth kinetics after palliative resection captured radiographically. PMID:27041470

  11. General Information about Renal Cell Cancer

    MedlinePlus

    ... Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

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

    SciTech Connect

    Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin; Fan, Jie

    2012-01-06

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

  13. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  14. Attenuation of krüppel-like factor 4 facilitates carcinogenesis by inducing g1/s phase arrest in clear cell renal cell carcinoma.

    PubMed

    Song, Erlin; Ma, Xin; Li, Hongzhao; Zhang, Peng; Ni, Dong; Chen, Weihao; Gao, Yu; Fan, Yang; Pang, Haigang; Shi, Taoping; Ding, Qiang; Wang, Baojun; Zhang, Yu; Zhang, Xu

    2013-01-01

    Krüppel-like factor 4 (KLF4) is a transcription factor with diverse functions in various cancer types; however, the function of KLF4 in clear cell renal cell carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially examined KLF4 expression by using a cohort of surgically removed ccRCC specimens and cell lines. Results indicated that the transcription and translation of KLF4 were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore, the KLF4 expression was significantly downregulated in the five ccRCC cell lines at protein and mRNA levels compared with that in normal renal proximal tubular epithelial cell lines (HKC). KLF4 downregulation was significantly correlated with tumor stage and tumor diameter. Promoter hypermethylation may contribute to its low expression. In addition, in vitro studies indicated that the KLF4 overexpression significantly inhibited proliferation in human ccRCC cell lines 786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle progress at the G1/S phase transition by upregulating p21 (WAF1/CIP1) expression and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the opposite. In vivo studies confirmed the anti-proliferative effect of KLF4. Our results suggested that KLF4 had an important function in suppressing the growth of ccRCC. PMID:23861801

  15. Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma

    PubMed Central

    Wu, Yong; Tan, Cong; Weng, Wei-Wei; Deng, Yu; Zhang, Qiong-Yan; Yang, Xiao-Qun; Gan, Hua-Lei; Wang, Tao; Zhang, Pei-Pei; Xu, Mi-Die; Wang, Yi-Qin; Wang, Chao-Fu

    2016-01-01

    Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven’t been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target. PMID:27186403

  16. Targeting Survivin Inhibits Renal Cell Carcinoma Progression and Enhances the Activity of Temsirolimus.

    PubMed

    Carew, Jennifer S; Espitia, Claudia M; Zhao, Weiguo; Mita, Monica M; Mita, Alain C; Nawrocki, Steffan T

    2015-06-01

    Elevated expression of the antiapoptotic factor survivin has been implicated in cancer cell survival and disease progression. However, its specific contribution to renal cell carcinoma (RCC) pathogenesis is not well defined. We investigated the roles of survivin in RCC tumor progression, resistance to mTOR inhibitors, and evaluated the therapeutic activity of the survivin suppressant YM155 in RCC models. Here, we report that survivin expression levels were significantly higher in RCC cell lines compared with normal renal cells. Stable targeted knockdown of survivin completely abrogated the ability of 786-O RCC tumors to grow in mice, thus demonstrating its importance as a regulator of RCC tumorigenesis. We next explored multiple strategies to therapeutically inhibit survivin function in RCC. Treatment with the mTOR inhibitor temsirolimus partially diminished survivin levels and this effect was augmented by the addition of YM155. Further analyses revealed that, in accordance with their combined anti-survivin effects, YM155 significantly improved the anticancer activity of temsirolimus in a panel of RCC cell lines in vitro and in xenograft models in vivo. Similar to pharmacologic inhibition of survivin, shRNA-mediated silencing of survivin expression not only inhibited RCC tumor growth, but also significantly sensitized RCC cells to temsirolimus therapy. Subsequent experiments demonstrated that the effectiveness of this dual survivin/mTOR inhibition strategy was mediated by a potent decrease in survivin levels and corresponding induction of apoptosis. Our findings establish survivin inhibition as a novel approach to improve RCC therapy that warrants further investigation. PMID:25808836

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

    SciTech Connect

    Li, Yuanyuan; Jia, Qingzhu; Zhang, Qian; Wan, Ying

    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.

  18. Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis

    PubMed Central

    Lim, Sharon; Lee, Se Jeong; Lim, Joung Eun; Nam, Do-Hyun; Joo, Kyeung Min; Jeong, Byong Chang; Jeon, Seong Soo; Choi, Han Yong; Lee, Hye Won

    2015-01-01

    Despite advances in the development of molecularly targeted therapies, metastatic renal cell carcinoma (RCC) is still incurable. Artesunate (ART), a well-known anti-malarial drug with low toxicity, exhibits highly selective anti-tumor actions against various tumors through generation of cytotoxic carbon-centered free radical in the presence of free iron. However, the therapeutic efficacy of ART against metastatic RCC has not yet been fully elucidated. In the analysis on a dataset from The Cancer Genome Atlas (TCGA) (n = 469) and a tissue microarray set from Samsung Medical Center (n = 119) from a cohort of patients with clear cell RCC (ccRCC), up-regulation of transferrin receptor 1 (TfR1), which is a well-known predictive marker for ART, was correlated with the presence of distant metastasis and an unfavorable prognosis. Moreover, ART exerted potent selective cytotoxicity against human RCC cell lines (Caki-1, 786-O, and SN12C-GFP-SRLu2) and sensitized these cells to sorafenib in vitro, and the extent of ART cytotoxicity correlated with TfR1 expression. ART-mediated growth inhibition of human RCC cell lines was shown to result from the induction of cell cycle arrest at the G2/M phase and oncosis-like cell death. Furthermore, ART inhibited cell clonogenicity and invasion of human RCC cells and anti-angiogenic effects in vitro in a dose-dependent manner. Consistent with these in vitro data, anti-tumor, anti-metastatic and anti-angiogenic effects of ART were also validated in human 786-O xenografts. Taken together, ART is a promising novel candidate for treating human RCC, either alone or in combination with other therapies. PMID:26426994

  19. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    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

  20. Immunotherapy in renal cell carcinoma.

    PubMed

    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

  1. Combination treatment with hypoxia-activated prodrug evofosfamide (TH-302) and mTOR inhibitors results in enhanced antitumor efficacy in preclinical renal cell carcinoma models

    PubMed Central

    Sun, Jessica D; Ahluwalia, Dharmendra; Liu, Qian; Li, Wenwu; Wang, Yan; Meng, Fanying; Bhupathi, Deepthi; Matteucci, Mark D; Hart, Charles P

    2015-01-01

    Tumors often consist of hypoxic regions which are resistant to chemo- and radiotherapy. Evofosfamide (also known as TH-302), a 2-nitroimidazole triggered hypoxia-activated prodrug, preferentially releases the DNA cross-linker bromo-isophosphoramide mustard in hypoxic cells. The intracellular kinase mTOR plays a key role in multiple pathways which are important in cancer progression. Here we investigated the enhanced efficacy profile and possible mechanisms of evofosfamide in combination with mTOR inhibitor (mTORi) everolimus or temsirolimus in renal cell carcinoma (RCC) xenograft models. The antitumor activities of the mTORi everolimus or temsirolimus alone, evofosfamide alone, or the combination were investigated in the 786-O and Caki-1 RCC cells in vitro and in vivo xenograft models. Two schedules were tested in which evofosfamide was started on the same day as the mTORi or 1 week after. Combination mechanisms were investigated by measuring a panel of pharmacodynamic biomarkers by immunohistochemistry. Antitumor efficacy in both RCC xenograft models was enhanced by the combination of evofosfamide and mTORi. Evofosfamide reduced the increased hypoxia induced by mTORi. Combination treatment induced increased DNA damage, decreased cell proliferation, and decreased survivin. Addition of mTORi did not change evofosfamide-mediated cytotoxicity in 786-O or Caki-1 cells in vitro which might suggest cell non-autonomous effects, specifically increased tumor hypoxia, are important for the in vivo combination activity. Taken together, evofosfamide potentiates the antitumor efficacy of mTOR inhibitors and inhibits the increased tumor hypoxia caused by mTOR inhibition. These studies provide a translational rationale for combining evofosfamide with mTOR inhibitors in clinical studies. PMID:26328245

  2. Unusual renal tumour: multilocular cystic renal cell carcinoma.

    PubMed

    Palmeiro, Marta Morna; Niza, João Luz; Loureiro, Ana Luisa; Conceição e Silva, João Paulo

    2016-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a rare presentation of renal cell carcinoma. Most patients are asymptomatic and frequently MCRCCs are detected incidentally. MCRCCs have good prognosis because of their low malignant potential. We report a case of a 39-year-old woman who presented with mild right flank pain and normal laboratory data. On imaging examinations, a Bosniak III cystic lesion was detected in the lower third of the right kidney. She underwent right partial nephrectomy and histopathology showed a multilocular cystic renal cell carcinoma Fuhrman grade 1. In this article, we also present a review of the literature on MCRCC, highlight the correlation of the pathological and imaging characteristics of these low aggressive renal lesions, and underscore the importance of their recognition to prevent unnecessary radical surgery. PMID:26957035

  3. Decreased expression of a novel lncRNA CADM1-AS1 is associated with poor prognosis in patients with clear cell renal cell carcinomas.

    PubMed

    Yao, Jie; Chen, Yang; Wang, Yongcheng; Liu, Shouying; Yuan, Xueling; Pan, Fei; Geng, Peiliang

    2014-01-01

    The clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinomas. Rapidly accumulating studies show that the long non-coding RNAs (lncRNAs) may play essential roles in cancers. In this study, we investigated the expression pattern of a novel lncRNA CADM1-AS1 in ccRCC by quantitative real time PCR. The results showed that CADM1-AS1 expression was down-regulated in tumor tissues in 64 patients with ccRCC compared with adjacent non-tumor tissues. Furthermore, the expression of CADM1-AS1 was positively correlated with the expression of mRNA CADM1 in ccRCC specimens (R = 0.611, P <0.0001). Decreased CADM1-AS1 expression was correlated with the progression of AJCC stage (P = 0.039) and worse survival of ccRCC patients (P <0.05). Also, multivariate analysis identified low CADM1-AS1 expression as an independent prognostic factor for ccRCC (P <0.001, HR = 0.211, 95% CI = 0.088-0.504). In addition, we used small interfering RNA (siRNA) to evaluate the biological function of CADM1-AS1 in vitro. The results showed that CADM1-AS1 expression was positively associated with CADM1 mRNA expression in 786-O cells and ACHN cells. Functional experiments demonstrated markedly enhanced ability of growth and migration, and reduced apoptotic rate in CADM1-AS1 knocking down in 786-O cells. Conversely, overexpression of CADM1-AS1 showed a significant decrease in growth and migration, along with an increase in apoptotic rate in ACHN cells. In conclusion, our data demonstrated CADM1-AS1 is a new tumor suppressor in ccRCC which regulates cell proliferation, apoptosis and migration via the expression pattern of "CADM1-AS1/CADM1 mRNA gene pairs". CADM1-AS1 may be a potential biomarker and therapeutic target in patients with ccRCC. PMID:25031695

  4. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma.

    PubMed

    Zhou, L; Liu, X-D; Sun, M; Zhang, X; German, P; Bai, S; Ding, Z; Tannir, N; Wood, C G; Matin, S F; Karam, J A; Tamboli, P; Sircar, K; Rao, P; Rankin, E B; Laird, D A; Hoang, A G; Walker, C L; Giaccia, A J; Jonasch, E

    2016-05-01

    Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and

  5. [Relationship of renal cell carcinoma and hypertension].

    PubMed

    Masanauskiene, Edita; Naudziūnas, Albinas; Jankauskiene, Laima; Unikauskas, Alvydas

    2009-01-01

    The morbidity and mortality due to renal cell carcinoma has increased worldwide over the last 30 years. Renal cell carcinoma accounts for about 90-95% of all renal tumors. The mean age of patients with this type of tumor ranges between 50 and 70 years. It is important to note that primary arterial hypertension as well as obesity and smoking are considered as independent risk factors for renal cell carcinoma. The increase in both systolic and diastolic blood pressure as well as the severity of arterial hypertension may have an impact on development of renal cell carcinoma. We describe the case of a 45-year-old male patient with hypertensive crisis. Computed tomography scan revealed renal cell carcinoma, which was confirmed histologically after surgical treatment. PMID:20173406

  6. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma

    PubMed Central

    Zhou, Lijun; Liu, Xian-De; Sun, Mianen; Zhang, Xuesong; German, Peter; Bai, Shanshan; Ding, Zhiyong; Tannir, Nizar; Wood, Christopher G; Matin, Surena F; Karam, Jose A; Tamboli, Pheroze; Sircar, Kanishka; Rao, Priya; Rankin, Erinn B.; Laird, Douglas A; Hoang, Anh G; Walker, Cheryl L; Giaccia, Amato J; Jonasch, Eric

    2016-01-01

    Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line, 786-O, was chronically treated with sunitinib, and assayed for AXL, MET, epithelial mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by shRNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets VEGFR, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT associated gene expression changes including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/HUVEC co-culture models. The suppression of AXL or MET expression, and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture, and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes pro-metastatic behavior and angiogenesis. The inhibition of AXL and MET

  7. Expression and functional role of miR-29b in renal cell carcinoma

    PubMed Central

    Xu, Yi; Zhu, Jianyong; Lei, Zhangming; Wan, Lijun; Zhu, Xiuwen; Ye, Feng; Tong, Yanyue

    2015-01-01

    Objectives: microRNAs (miRNAs) play essential roles in many tumors, including renal cell carcinoma (RCC). The aim of the present study was to investigate the expression and functional role of miR-29b in RCC and to identify its target genes. Methods: We determined the expression of miR-29b in clear cell RCC (ccRCC) tissues and RCC cell lines (786-O, A498, and SN12-PM6) using quantitative real-time PCR (qRT-PCR). The associations between miR-29b expression and clinical pathological parameters and prognosis were explored. Besides, the role of miR-29b in the SN12-PM6 cells proliferation, apoptosis, cycle, and invasion were investigated after transduction with lentivirus vectors. The kines in family member 1B (KIF1B), possible miR-29b target genes, were predicted using bioinformatics approaches, as well as the role in the pathogenesis of RCC. Results: Elevated expression of miR-29b was found in both tumor tissues and cell lines. High expression of miR-29b was significantly associated with tumor-node-metastasis (TNM) stage (P = 0.026) and the overall survival (P = 0.009) in the ccRCC. Inhibition of miR-29b expression could promote apoptosis, and inhibit proliferation and invasion ability in SN12-PM6 cells. Also, we confirmed that miR-29b could directly regulate the expression of KIF1B at the post transcriptional level. Conclusion: These data suggest that miR-29b acts as an oncomiR, promoting proliferation and invasion ability through KIF1B suppression, and it might be a potential marker for prognosis of RCC. PMID:26823729

  8. Computational repositioning and preclinical validation of pentamidine for renal cell cancer

    PubMed Central

    de Vasconcellos, Jaira F.; Paccez, Juliano D.; Gu, Xuesong; Kung, Andrew L.; Libermann, Towia A.

    2014-01-01

    While early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. We previously established a highly accurate signature of differentially expressed genes that distinguish ccRCC from normal kidney. The purpose of the current study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anti-cancer therapy. Here we demonstrate that one of the drugs predicted to revert the RCC gene signature towards normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. ccRCC-specific gene expression signatures of individual patients were used to query the C-MAP software. Eight drugs with negative correlation and p-value <0.05 were analyzed for efficacy against RCC in vitro and in vivo. Our data demonstrate consistency across most ccRCC patients for the set of high scoring drugs. Most of the selected high scoring drugs potently induce apoptosis in RCC cells. Several drugs also demonstrate selectivity for VHL negative RCC cells. Most importantly, at least one of these drugs, pentamidine, slows tumor growth in the 786-O human ccRCC xenograft mouse model. Our findings suggest that pentamidine might be a new therapeutic agent to be combined with current standard-of-care regimens for metastatic ccRCC patients and support our notion that IBA combined with C-MAP analysis enables repurposing of FDA-approved drugs for potential anti-RCC therapy. PMID:24785412

  9. Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK and mTOR inhibitions in renal cancer cells.

    PubMed

    Suzuki, Kenjiro; Mizuno, Ryuichi; Suenaga, Kiyotake; Teruya, Toshiaki; Tanaka, Nobuyuki; Kosaka, Takeo; Oya, Mototsugu

    2013-02-01

    Advanced renal cell carcinoma (RCC) remains an incurable disease, and newer anticancer drugs are needed. Bisebromoamide, a novel cytotoxic peptide, was isolated from the marine cyanobacterium Lyngbya species at our laboratory in 2009. This compound specifically inhibited the phosphorylation of ERK in platelet-derived growth factor-activated normal rat kidney cells. The aim of this study was to evaluate the effect and elucidate the potential mechanism of Bisebromoamide actions on human RCC cells. Two renal cancer cell lines, 769-P and 786-O, were used. The effects of Bisebromoamide were analyzed employing assays for water-soluble Tetrazolium-1 salts. Apoptosis was determined by flow cytometric TUNEL analysis. Cell-cycle distributions were analyzed by flow cytometry using BrdU/propidium iodide (PI) staining. Kinases of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) pathway and Raf/MEK/ERK pathway were analyzed by Western blotting. After Bisebromoamide treatment for 48 and 72 h, cell viability was significantly decreased in both cell lines at 1 and 10 μmol/L. After treatment with 1 μmol/L Bisebromoamide for 72 h, apoptosis and the increased percentage of cells in the sub-G1 phase were observed in both cell lines. Bisebromoamide inhibited the phosphorylation of ERK and Akt in both cell lines tested. Similar effects were demonstrated for phosphorylation of mTOR and p70 S6. Bisebromoamide is a promising potential agent against RCC due to its ability to inhibit both the Raf/MEK/ERK and PI3K/Akt/mTOR pathways. PMID:24133625

  10. Sickle cell disease: renal manifestations and mechanisms

    PubMed Central

    Nath, Karl A.; Hebbel, Robert P.

    2015-01-01

    Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

  11. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  12. Sunitinib benefits patients with renal cell carcinoma

    Cancer.gov

    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.

  13. The Tumor Suppressor pVHL Down-regulates Never-in-Mitosis A-related Kinase 8 via Hypoxia-inducible Factors to Maintain Cilia in Human Renal Cancer Cells*

    PubMed Central

    Ding, Xiao-Fei; Zhou, Jun; Hu, Qiong-Ying; Liu, Shuang-Chun; Chen, Guang

    2015-01-01

    NEK8 (never in mitosis gene A (NIMA)-related kinase 8) is involved in cytoskeleton, cilia, and DNA damage response/repair. Abnormal expression and/or dysfunction of NEK8 are related to cancer development and progression. However, the mechanisms that regulate NEK8 are not well declared. We demonstrated here that pVHL may be involved in regulating NEK8. We found that CAK-I cells with wild-type vhl expressed a lower level of NEK8 than the cells loss of vhl, such as 786-O, 769-P, and A-498 cells. Moreover, pVHL overexpression down-regulated the NEK8 protein in 786-O cells, whereas pVHL knockdown up-regulated NEK8 in CAK-I cells. In addition, we found that the positive hypoxia response elements (HREs) are located in the promoter of the nek8 sequence and hypoxia could induce nek8 expression in different cell types. Consistent with this, down-regulation of hypoxia-inducible factors α (HIF-1α or HIF-2α) by isoform-specific siRNA reduced the ability of hypoxia inducing nek8 expression. In vivo, NEK8 and HIF-1α expression were increased in kidneys of rats subjected to an experimental hypoxia model of ischemia and reperfusion. Furthermore, NEK8 siRNA transfection significantly blocked pVHL-knockdown-induced cilia disassembling, through impairing the pVHL-knockdown-up-regulated NEK8 expression. These results support that nek8 may be a novel hypoxia-inducible gene. In conclusion, our findings show that nek8 may be a new HIF target gene and pVHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells. PMID:25451921

  14. The tumor suppressor pVHL down-regulates never-in-mitosis A-related kinase 8 via hypoxia-inducible factors to maintain cilia in human renal cancer cells.

    PubMed

    Ding, Xiao-Fei; Zhou, Jun; Hu, Qiong-Ying; Liu, Shuang-Chun; Chen, Guang

    2015-01-16

    NEK8 (never in mitosis gene A (NIMA)-related kinase 8) is involved in cytoskeleton, cilia, and DNA damage response/repair. Abnormal expression and/or dysfunction of NEK8 are related to cancer development and progression. However, the mechanisms that regulate NEK8 are not well declared. We demonstrated here that pVHL may be involved in regulating NEK8. We found that CAK-I cells with wild-type vhl expressed a lower level of NEK8 than the cells loss of vhl, such as 786-O, 769-P, and A-498 cells. Moreover, pVHL overexpression down-regulated the NEK8 protein in 786-O cells, whereas pVHL knockdown up-regulated NEK8 in CAK-I cells. In addition, we found that the positive hypoxia response elements (HREs) are located in the promoter of the nek8 sequence and hypoxia could induce nek8 expression in different cell types. Consistent with this, down-regulation of hypoxia-inducible factors α (HIF-1α or HIF-2α) by isoform-specific siRNA reduced the ability of hypoxia inducing nek8 expression. In vivo, NEK8 and HIF-1α expression were increased in kidneys of rats subjected to an experimental hypoxia model of ischemia and reperfusion. Furthermore, NEK8 siRNA transfection significantly blocked pVHL-knockdown-induced cilia disassembling, through impairing the pVHL-knockdown-up-regulated NEK8 expression. These results support that nek8 may be a novel hypoxia-inducible gene. In conclusion, our findings show that nek8 may be a new HIF target gene and pVHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells. PMID:25451921

  15. How Kidney Cell Death Induces Renal Necroinflammation.

    PubMed

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

    2016-05-01

    The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. PMID:27339382

  16. Everolimus in renal cell carcinoma.

    PubMed

    Wang, Y

    2010-08-01

    Everolimus (also known as RAD-001; Afinitor®) is an orally active inhibitor of the intracellular protein kinase mammalian target of rapamycin. The U.S. Food and Drug Administration and the European Medicines Agency recently approved everolimus for the treatment of advanced renal cell carcinoma (RCC) on the basis of the results of a randomized phase III clinical trial. In the trial, 10 mg daily everolimus was effective and well tolerated by patients with advanced RCC, whose disease had progressed while under the treatment with sunitinib and/or sorafenib. Everolimus treatment led to 36% of 6-month progression-free survival (PFS) rate and 31% of 3-month PFS rate. Most of the adverse events were mild to moderate (grade 1-2) in severity. The most frequent grade 3-4 adverse events were stomatitis, fatigue, pneumonitis and infections. Clinical trials on everolimus in combination with sunitinib, sorafenib, imatinib and vatalanib for the treatment of RCC are ongoing. PMID:20830316

  17. Emerging surgical treatments for renal cell carcinoma.

    PubMed

    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

  18. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    PubMed Central

    Berquist, Sean W.; Hassan, Abd-elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H.

    2016-01-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  19. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    PubMed

    Berquist, Sean W; Hassan, Abd-Elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H

    2016-05-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  20. Metastatic renal cell carcinoma in the nasopharynx.

    PubMed

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment. PMID:23924557

  1. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma †

    PubMed Central

    Lin, Chen-Sung; Lee, Hui-Ting; Lee, Ming-Huei; Pan, Siao-Cian; Ke, Chen-Yeh; Chiu, Allen Wen-Hsiang; Wei, Yau-Huei

    2016-01-01

    We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0

  2. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma.

    PubMed

    Lin, Chen-Sung; Lee, Hui-Ting; Lee, Ming-Huei; Pan, Siao-Cian; Ke, Chen-Yeh; Chiu, Allen Wen-Hsiang; Wei, Yau-Huei

    2016-01-01

    We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XF(e)-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0

  3. Pulmonary manifestations of renal cell carcinoma.

    PubMed

    Agrawal, Abhinav; Sahni, Sonu; Iftikhar, Asma; Talwar, Arunabh

    2015-12-01

    Renal cell carcinoma (RCC) accounts for majority of all primary renal neoplasms. Classic manifestations of RCC include the triad of flank pain, hematuria and a palpable renal mass. Patients with RCC can develop various extra renal manifestations including involvements of the lungs, inferior vena cava, liver and the bones. The pulmonary manifestations of renal cell carcinoma include metastatic disease including endobronchial, pleural, parenchymal or lymph node metastasis, pleural effusion or hemothorax. Pulmonary embolism and tumor embolism is another common manifestation of renal cell carcinoma. RCC is a highly vascular tumor and can cause pulmonary arterio-venous fistulas leading to high output failure. Rarely, RCC can also present with paraneoplastic presentations including cough or bilateral diaphragm paralysis. Drugs used to treat RCC have been associated with drug related pneumonitis and form an important differential diagnosis in patients with RCC on therapy presenting with shortness of breath. In this review we discuss the various pulmonary manifestations of RCC. A high index of suspicion with these presentations can lead to an early diagnosis and assist in instituting an appropriate intervention. PMID:26525375

  4. Renal cell carcinoma: Evolving and emerging subtypes.

    PubMed

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-12-16

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  5. Renal cell carcinoma: Evolving and emerging subtypes

    PubMed Central

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-01-01

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  6. Evolving Immunotherapy Approaches for Renal Cell Carcinoma.

    PubMed

    Curtis, Susanna A; Cohen, Justine V; Kluger, Harriet M

    2016-09-01

    Metastatic renal cell carcinoma (mRCC) continues to be associated with high rates of morbidity and mortality. Renal cell carcinoma (RCC) is typically resistant to cytotoxic chemotherapy, and while targeted therapies have activity and prolong progression-free and overall survival, responses are usually not durable. Modulating the immune system with cytokine therapy, vaccine therapy, cell therapy, and checkpoint inhibitors offers hope of prolonged survival. Standard and emerging immune therapy approaches and combinations of immune therapies and other modalities are reviewed. PMID:27475806

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

    PubMed

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

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

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

    PubMed Central

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

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC. PMID:26029303

  9. The evolving classification of renal cell neoplasia.

    PubMed

    Delahunt, Brett; Srigley, John R

    2015-03-01

    The classification of renal cell neoplasia is morphologically based; however, this has evolved over the last 35 years with the incorporation of genetic characteristics into the diagnostic features of some tumors. The 2013 Vancouver classification recognized 17 morphotypes of renal parenchymal malignancy and two benign tumors. This classification included the newly established entities tubulocystic renal cell carcinoma (RCC)), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family translocation RCC and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition to these newly described forms of RCC there are a number of novel tumors that are currently recognized as emerging entities. These are likely to be incorporated into subsequent classifications and include thyroid-like follicular RCC, succinate dehydrogenase B mutation-associated RCC, ALK translocation RCC, tuberous sclerosis complex-associated RCC, and RCC with (angio) leiomyomatous stroma. PMID:25753529

  10. Renal Cell Carcinoma Arising From Renal Allograft Detected by 18F-FDG PET-CT.

    PubMed

    Guo, Yuehong; Wang, Tie

    2016-05-01

    Renal cell carcinoma arising from renal allograft is a rare condition. A 56-year-old man with a history of 3 renal transplantation due to renal failure presented poor appetite and weight loss for 3 months. Possibility of tumor of unknown origin was suspected. For this reason, an FDG PET/CT was performed, and the images showed a hypermetabolic focus in the lower pole of the left renal transplant, suggestive of a malignant lesion. Subsequent pathological examination following allograft nephrectomy confirmed grade 4 renal cell carcinoma. PMID:26825198

  11. Therapeutic challenges in renal cell carcinoma

    PubMed Central

    Penticuff, Justin C; Kyprianou, Natasha

    2015-01-01

    Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of “targeted therapies”. Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states. This review discusses the current understanding of diagnostic challenges and the mechanism-based clinical evidence on therapeutic management of advanced RCC. PMID:26309897

  12. MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma

    PubMed Central

    2012-01-01

    Background A growing body of evidence suggests that microRNAs (miRNAs) play an important role in cancer diagnosis and therapy. MicroRNA-99a (miR-99a), a potential tumor suppressor, is downregulated in several human malignancies. The expression and function of miR-99a, however, have not been investigated in human renal cell carcinoma (RCC) so far. We therefore examined the expression of miR-99a in RCC cell lines and tissues, and assessed the impact of miR-99a on the tumorigenesis of RCC. Methods MiR-99a levels in 40 pairs of RCC and matched adjacent non-tumor tissues were assessed by real-time quantitative Reverse Transcription PCR (qRT-PCR). The RCC cell lines 786-O and OS-RC-2 were transfected with miR-99a mimics to restore the expression of miR-99a. The effects of miR-99a were then assessed by cell proliferation, cell cycle, transwell, and colony formation assay. A murine xenograft model of RCC was used to confirm the effect of miR-99a on tumorigenicity in vivo. Potential target genes were identified by western blotting and luciferase reporter assay. Results We found that miR-99a was remarkably downregulated in RCC and low expression level of miR-99a was correlated with poor survival of RCC patients. Restoration of miR-99a dramatically suppressed RCC cells growth, clonability, migration and invasion as well as induced G1-phase cell cycle arrest in vitro. Moreover, intratumoral delivery of miR-99a could inhibit tumor growth in murine xenograft models of human RCC. In addition, we also fond that mammalian target of rapamycin (mTOR) was a direct target of miR-99a in RCC cells. Furthermore, siRNA-mediated knockdown of mTOR partially phenocopied the effect of miR-99a overexpression, suggesting that the tumor suppressive role of miR-99a may be mediated primarily through mTOR regulation. Conclusions Collectively, these results demonstrate for the first time, to our knowledge, that deregulation of miR-99a is involved in the etiology of RCC partially via direct targeting

  13. EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling.

    PubMed

    Pan, Xiu-Wu; Chen, Lu; Hong, Yi; Xu, Dan-Feng; Liu, Xi; Li, Lin; Huang, Yi; Cui, Li-Ming; Gan, Si-Shun; Yang, Qi-Wei; Huang, Hai; Qu, Fa-Jun; Ye, Jian-Qing; Wang, Lin-Hui; Cui, Xin-Gang

    2016-06-01

    There are no effective therapies for advanced renal cell carcinoma (RCC), except for VEGFR inhibitors with only ~50% response rate. To identify novel targets and biomarkers for RCC is of great importance in treating RCC. In this study, we observed that eukaryotic initiation factor 3d (EIF3D) expression was significantly increased in RCC compared with paracarcinoma tissue using immunohistochemistry staining and western blot analysis. Furthermore, bioinformatics meta-analysis using ONCOMINE microarray datasets showed that EIF3D mRNA expressions in CCRCC tissue specimens were significantly higher than that in normal tissue specimens. In addition, RCC tissue microarray demonstrated that elevated EIF3D expression was positively correlated with TNM stage and tumor size. EIF3D silencing in human 786-O and ACHN CCRCC cell lines by RNA interference demonstrated that EIF3D knockdown obviously inhibited cell proliferation and colony formation, caused G2/M arrest through downregulation of Cyclin B1 and Cdk1 and upregulation of p21, and induced apoptosis shown by sub-G1 accumulation and RARP cleavage. Moreover, correlation analysis using ONCOMINE microarray datasets indicated that increased EIF3D mRNA expression was positively correlated to PCNA, Cyclin B1 and CDK1 mRNA expression in RCC. Collectively, these results provide reasonable evidences that EIF3D may function as a potential proto-oncogene that participates in the occurrence and progression of RCC. PMID:27035563

  14. Clear cell papillary renal cell carcinoma: a potential mimic of conventional clear cell renal carcinoma on core biopsy.

    PubMed

    Liddell, Heath; Mare, Anton; Heywood, Sean; Bennett, Genevieve; Chan, Hin Fan

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) is a recently described, relatively uncommon variant of renal cell carcinoma (RCC) with a reported incidence of 4.1%. Thought to only arise in those with end stage renal disease, CCP-RCC is increasingly identified in those without renal impairment. CCP-RCCs have unique morphologic, genetic, and immunohistochemical features distinguishing them from both conventional clear cell renal cell carcinomas and papillary renal cell carcinomas. Immunohistochemically, these tumors are positive for CK7 and negative for CD10 and racemase. This is in contrast to conventional cell renal cell carcinomas (CK7 negative, CD10 positive) and papillary cell carcinomas (CK7, CD10, and racemase positive). These tumours appear to be indolent in nature, with no current documented cases of metastatic spread. We present the case of a 42-year-old female who presented with an incidental finding of a renal mass that on a core biopsy was reported as clear cell carcinoma, Fuhrman grade 1. She subsequently underwent a radical nephrectomy and further histological examination revealed the tumor to be a clear cell papillary renal cell carcinoma, Fuhrman grade 1. PMID:25709850

  15. Ablative therapies in renal cell carcinoma.

    PubMed

    Chan, A A; Ahrar, K; Matin, S F

    2011-09-01

    We reviewed the use of ablative therapies in the management of renal cell carcinoma. We performed a PubMed search of the English language literature using the keywords "ablation" and "renal carcinoma." Pertinent articles specific to the technologic advancement of ablative therapy and clinical outcomes were selected for review. Intermediate-term oncologic outcomes of cryoablation and radiofrequency ablation are acceptable but are not quite as good as for surgical excision based nearly all on retrospective studies. No randomized studies have been performed comparing excisional and ablative therapies. Careful selection of patients and tumor characteristics results in improved outcomes. Diagnostic biopsy for tissue confirmation is mandatory and should even be considered post therapy after 6-12 months in patients with a concern about recurrence. Ablative therapies are associated with decreased morbidity, less severe complication rates, and excellent preservation of renal function in comparison with surgical excision. The majority of recurrences occur early, but long-term surveillance is required as delayed recurrences are also possible and the long-term oncologic efficacy is not yet established. Ablation can be delivered percutaneously or laparoscopically, and the superiority of one over the other remains controversial. The percutaneous approach is more cost effective and causes less perinephric desmoplasia. Nearly all data on ablation are retrospective and, with few exceptions, from single institutions. Ablative therapy is an appealing option for the management of small renal tumors shown to be renal cell carcinoma on biopsy in patients who are unsuitable candidates for surgical extirpation. PMID:21993322

  16. SnapShot: Renal Cell Carcinoma.

    PubMed

    Turajlic, Samra; Larkin, James; Swanton, Charles

    2015-12-01

    This SnapShot summarizes current knowledge about the key features in mutational landscape, major pathways, and tumor evolution and heterogeneity in renal cell carcinoma, as well as the most recent advances in therapeutic development. To view this SnapShot, open or download the PDF. PMID:26638079

  17. Resistance of Renal Cell Carcinoma to Sorafenib Is Mediated by Potentially Reversible Gene Expression

    PubMed Central

    Schor-Bardach, Rachel; Wang, Xiaoen; Collins, Michael P.; Panka, David; Putheti, Prabhakar; Signoretti, Sabina; Alsop, David C.; Libermann, Towia; Atkins, Michael B.; Mier, James W.; Goldberg, S. Nahum; Bhatt, Rupal S.

    2011-01-01

    Purpose Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. Experimental Design Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. Results Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. Conclusions In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment. PMID:21559452

  18. Diagnostic value of routine bone scintigraphy renal imaging in renal cell carcinoma

    SciTech Connect

    Chancellor, M.B.; Konnak, J.W.; Grossman, H.B.

    1989-05-01

    Technetium-99m-phosphate compounds used in bone scanning are excreted by the kidney, and excellent renal images can be obtained on routine bone scintigrams. The preoperative bone scans of 49 patients who underwent radical nephrectomy for renal cell carcinoma between 1981 and 1985 were reviewed for renal imaging. Ninety-four percent of the patients had abnormal bone scan renal images (82% had focal decreased uptake, and 12% had focal increased uptake). Six percent of the renal images were symmetrical bilaterally. When bone scans are employed in the postoperative follow-up of patients with renal cancer, they can be used to assess the status of the remaining kidney.

  19. Hereditary leiomyomatosis and renal cell carcinoma

    PubMed Central

    Schmidt, Laura S; Linehan, W Marston

    2014-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic acid cycle enzyme fumarate hydratase (FH). HLRCC patients are predisposed to develop cutaneous leiomyomas, multiple, symptomatic uterine fibroids in young women resulting in early hysterectomies, and early onset renal tumors with a type 2 papillary morphology that can progress and metastasize, even when small. Since HLRCC-associated renal tumors can be more aggressive than renal tumors in other hereditary renal cancer syndromes, caution is warranted, and surgical intervention is recommended rather than active surveillance. At-risk members of an HLRCC family who test positive for the familial germline FH mutation should undergo surveillance by annual magnetic resonance imaging from the age of 8 years. Biochemical studies have shown that FH-deficient kidney cancer is characterized by a metabolic shift to aerobic glycolysis. It is hoped that through ongoing clinical trials evaluating targeted molecular therapies, an effective form of treatment for HLRCC-associated kidney cancer will be developed that will offer an improved prognosis for individuals affected with HLRCC-associated kidney cancer. PMID:25018647

  20. Hereditary leiomyomatosis and renal cell carcinoma.

    PubMed

    Schmidt, Laura S; Linehan, W Marston

    2014-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic acid cycle enzyme fumarate hydratase (FH). HLRCC patients are predisposed to develop cutaneous leiomyomas, multiple, symptomatic uterine fibroids in young women resulting in early hysterectomies, and early onset renal tumors with a type 2 papillary morphology that can progress and metastasize, even when small. Since HLRCC-associated renal tumors can be more aggressive than renal tumors in other hereditary renal cancer syndromes, caution is warranted, and surgical intervention is recommended rather than active surveillance. At-risk members of an HLRCC family who test positive for the familial germline FH mutation should undergo surveillance by annual magnetic resonance imaging from the age of 8 years. Biochemical studies have shown that FH-deficient kidney cancer is characterized by a metabolic shift to aerobic glycolysis. It is hoped that through ongoing clinical trials evaluating targeted molecular therapies, an effective form of treatment for HLRCC-associated kidney cancer will be developed that will offer an improved prognosis for individuals affected with HLRCC-associated kidney cancer. PMID:25018647

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

    PubMed

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

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. PMID:27259369

  2. Pseudotumor presentation of renal tuberculosis mimicking renal cell carcinoma: A rare entity

    PubMed Central

    Panwar, Anubhav; Ranjan, Raju; Drall, Nityasha; Mishra, Neha

    2016-01-01

    Tuberculosis can involve any part of the body. Urogenital tuberculosis is a fairly common extra-pulmonary manifestation of tuberculosis and renal tuberculosis is the most common form of urogenital tuberculosis. Renal tuberculosis seldom presents as a mass, usually due to hydronephrosis of the involved kidney. However in extremely rare cases it may present as an inflammatory pseudotumor which may mimic renal cell carcinoma. We present a case of a 65- year- old male who was provisionally diagnosed as renal cell carcinoma based on clinical and radiological findings and managed accordingly but was finally diagnosed as renal tuberculosis based on histopathological examination of surgical specimen.

  3. The cell biology of renal filtration

    PubMed Central

    Quaggin, Susan E.

    2015-01-01

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

  4. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man.

    PubMed

    Pandya, V K; Sutariya, H C

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved the upper pole of the transplant. There was no metastasis. The patient underwent radical allograft nephrectomy for the carcinoma that had extended up to the renal hilum. Histopathological examination revealed Furhman grade-1, clear cell variant, stage pT2 N0 M0. In the last visit, the patient was on maintenance hemodialysis via arterio-venous fistula and planned for cadaveric renal transplantation. Computed tomography could facilitate early diagnosis and proper management of patients with post-renal allograft renal cell carcinoma. PMID:26889374

  5. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man

    PubMed Central

    Pandya, V. K.; Sutariya, H. C.

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved the upper pole of the transplant. There was no metastasis. The patient underwent radical allograft nephrectomy for the carcinoma that had extended up to the renal hilum. Histopathological examination revealed Furhman grade-1, clear cell variant, stage pT2 N0 M0. In the last visit, the patient was on maintenance hemodialysis via arterio-venous fistula and planned for cadaveric renal transplantation. Computed tomography could facilitate early diagnosis and proper management of patients with post-renal allograft renal cell carcinoma. PMID:26889374

  6. Cooperative Effect of miR-141-3p and miR-145-5p in the Regulation of Targets in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Liep, Julia; Kilic, Ergin; Meyer, Hellmuth A.; Busch, Jonas; Jung, Klaus; Rabien, Anja

    2016-01-01

    Background Due to the poor prognosis for advanced renal cell carcinoma (RCC), there is an urgent need for new therapeutic targets and for prognostic markers to identify high risk tumors. MicroRNAs (miRNAs) are frequently dysregulated in tumors, play a crucial role during carcinogenesis and therefore might be promising new biomarkers. In previous studies, we identified miR-141-3p and miR-145-5p to be downregulated in clear cell RCC (ccRCC). Our objective was to investigate the functional association of these miRNAs, focusing on the cooperative regulation of new specific targets and their role in ccRCC progression. Methods The effect of miR-141-3p and miR-145-5p on cell migration was examined by overexpression in 786-O cells. New targets of both miRNAs were identified by miRWalk, validated in 786-O and ACHN cells and additionally characterized in ccRCC tissue on mRNA and protein level. Results In functional analysis, a tumor suppressive effect of miR-141-3p and miR-145-5p by decreasing migration and invasion of RCC cells could be shown. Furthermore, co-overexpression of the miRNAs seemed to result in an increased inhibition of cell migration. Both miRNAs were recognized as post-transcriptional regulators of the targets EAPP, HS6ST2, LOX, TGFB2 and VRK2. Additionally, they showed a cooperative effect again as demonstrated by a significantly increased inhibition of HS6ST2 and LOX expression after simultaneous overexpression of both miRNAs. In ccRCC tissue, LOX mRNA expression was strongly increased compared to normal tissue, allowing also to distinguish between non-metastatic and already metastasized primary tumors. Finally, in subsequent tissue microarray analysis LOX protein expression showed a prognostic relevance for the overall survival of ccRCC patients. Conclusion These results illustrate a jointly strengthening effect of the dysregulated miR-141-3p and miR-145-5p in various tumor associated processes. Focusing on the cooperative effect of miRNAs provides new

  7. Histone modifications: implications in renal cell carcinoma

    PubMed Central

    Ramakrishnan, Swathi; Ellis, Leigh; Pili, Roberto

    2013-01-01

    In 2012, an estimated 64,770 men and women were diagnosed with malignancy of the kidney and renal pelvis, of which 13,570 succumbed to their disease. Common genetic aberrations in renal cell carcinomas (RCCs) include loss of function of the VHL gene in clear-cell RCC, overexpression of the c-MET gene in papillary RCC type I, deficiency in the FH gene in papillary RCC type II and loss of heterozygozity of the BHD gene in chromophobe RCC. Recent studies illustrate epigenetic silencing of VHL, as well as alterations in histone modifications and their governing enzymes. The possibility of reversing these epigenetic marks has resulted in efforts to target these changes by utilizing inhibitors of HDACs, DNA methyltransferases and, recently, histone methyltransferases in preclinical and clinical studies. This article focuses on potential therapeutic interventions, and the implications of histone modifications and related enzyme alterations in RCC. PMID:23895657

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

    PubMed Central

    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

  9. Renal cell carcinoma and autoimmune hemolytic anemia.

    PubMed

    Lands, R; Foust, J

    1996-04-01

    A previously healthy man who became bedridden because of malaise, fatigue, and weakness was found to have an autoimmune hemolytic anemia (AIHA). In the course of his evaluation for the AIHA, he was found, coincidentally, to have a renal cell carcinoma. The AIHA was marginally responsive to therapy with corticosteroids, but it resolved promptly after excision of the cancer. This case represents probably a rarely observed association between a nonhematologic malignancy and autoimmune hemolytic anemia. PMID:8614893

  10. SnapShot: Renal Cell Carcinoma.

    PubMed

    Ricketts, Christopher J; Crooks, Daniel R; Sourbier, Carole; Schmidt, Laura S; Srinivasan, Ramaprasad; Linehan, W Marston

    2016-04-11

    Renal cell carcinoma (RCC) is a heterogeneous disease made up of a number of different cancer types, with distinct histologies, clinical courses, therapeutic responses, and genetic drivers. Germline mutations in 14 genes have been associated with increased risk of RCC and can result in HIF pathway activation, chromatin dysregulation, and altered metabolism. Knowledge of these pathway alterations can inform the development of targeted therapeutic approaches. To view this SnapShot, open or download the PDF. PMID:27070709

  11. Thyroid Hormones as Renal Cell Cancer Regulators

    PubMed Central

    Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829

  12. Scalp metastases of a renal cell carcinoma.

    PubMed

    Estrada-Chavez, Guadalupe; Vega-Memije, Maria Elisa; Lacy-Niebla, Rosa Maria; Toussaint-Caire, Sonia

    2006-01-01

    An 80-year-old man presented with a localized tumor of the right occipital scalp. The tumor was a 1-cm, bright red-purple, ulcerated, and crusted exophytic nodule on a smooth base (Figure 1). The lesion had grown asymptomatically over 18 months except for profuse bleeding induced by minimal trauma. It was extirpated with the clinical diagnosis of pyogenic granuloma vs. renal metastasis to the scalp. The patient's medical history included a transurethral prostatic resection 3 years earlier and, 1 year later, a right nephrectomy for a 2-kg kidney tumor verbally reported as "benign." The patient also had a 2-year history of untreated high blood pressure. Histopathologically, the excised tissue was an exo-endophytic nodule of a solid form composed of pleomorphic neoplastic cells with abundant clear cytoplasm, surrounded by fibrous collagen septae, blood vessel proliferation, and areas of hemorrhage (Figures 2 and 3). The histopathologic diagnosis of metastatic renal cell carcinoma was supported by immunohistochemistry with positive epithelial membrane antigen staining (Figure 4). Cytokeratins 7 and 20 were nonreactive. Laboratory studies revealed hematuria and elevated creatinine and urea nitrogen levels, but no malignant cells were observed in five urinary cytologies. Renal ultrasound showed the presence of two simple cysts in the left kidney and data compatible with chronic inflammatory disease. PMID:16687987

  13. Renal Cell Carcinoma in Tuberous Sclerosis Complex

    PubMed Central

    Yang, Ping; Cornejo, Kristine M.; Sadow, Peter M.; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L.; Feldman, Adam S.; Paul, Elahna; Thiele, Elizabeth A.; Yu, Jane J.; Henske, Elizabeth P.; Kwiatkowski, David J.; Young, Robert H.; Wu, Chin-Lee

    2014-01-01

    Renal cell carcinoma (RCC) occurs in 2-4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathological and molecular features, enabling separation of these 46 tumors into three groups. The largest subset of tumors (n=24) had a distinct morphological, immunological and molecular profile, including prominent papillary architecture and uniformly deficient SDHB expression prompting the novel term “TSC-associated papillary RCC.” The second group (n=15) was morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT) while the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated papillary RCCs (PRCC) had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were the International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCC showed strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and were uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  14. Renal cell carcinoma in tuberous sclerosis complex.

    PubMed

    Yang, Ping; Cornejo, Kristine M; Sadow, Peter M; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L; Feldman, Adam S; Paul, Elahna; Thiele, Elizabeth A; Yu, Jane J; Henske, Elizabeth P; Kwiatkowski, David J; Young, Robert H; Wu, Chin-Lee

    2014-07-01

    Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  15. Pulmonary Metastasectomy 31 Years After Surgery for Renal Cell Carcinoma.

    PubMed

    Watanabe, Yui; Harada, Aya; Aoki, Masaya; Kamimura, Go; Wakida, Kazuhiro; Nagata, Toshiyuki; Yokomakura, Naoya; Kariatsumari, Kota; Nakamura, Yoshihiro; Sato, Masami

    2015-06-01

    An 82-year-old man underwent a left upper lobectomy for a solitary tumor on suspicion of lung cancer. Histopathologic findings of the resected specimen showed clear cell renal cell carcinoma, which was diagnosed as a metastasis from kidney cancer concealed for 31 years after nephrectomy. The Ki-67 labeling index of the metastatic tumor was high (36.1%). A few cases of recurrent renal cell carcinoma after a long interval from initial diagnosis have been seen. However, pulmonary metastasectomy more than 30 years after radical nephrectomy for renal cell carcinoma has not been reported. This remarkable case provides new and valuable clinical insights into metastatic renal cell carcinoma. PMID:26046874

  16. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

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

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas. PMID:27232353

  18. Sciatica leading to the discovery of a renal cell carcinoma

    PubMed Central

    Amine Lakmichi, Mohamed; Jarir, Redouane; Kabour, Jamal; Dahami, Zakaria; Said Moudouni, Mohamed; Sarf, Ismail

    2011-01-01

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, leading to the discovery of a renal cell carcinoma. Although uncommon, renal cell carcinoma spine metastasis should be included in the differential diagnosis of back pain and sciatica. PMID:22355428

  19. Sciatica leading to the discovery of a renal cell carcinoma.

    PubMed

    Lakmichi, Mohamed Amine; Jarir, Redouane; Kabour, Jamal; Dahami, Zakaria; Said Moudouni, Mohamed; Sarf, Ismail

    2011-01-01

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, leading to the discovery of a renal cell carcinoma. Although uncommon, renal cell carcinoma spine metastasis should be included in the differential diagnosis of back pain and sciatica. PMID:22355428

  20. A Giant Intra Abdominal Mass Mimicking Renal Cell Carcinoma: A Rare Presentation of Renal Angiomyolipoma.

    PubMed

    Haque, M E; Rahman, M A; Kaisar, I; Islam, M F; Salam, M A

    2016-07-01

    Angiomyolipoma (AML) is a benign tumor commonly found in kidney than extra renal sites. Most of the small renal angiomyolipomas are diagnosed incidentally on ultrasound and other imaging studies. Some renal AMLs present clinically when become very big, giant renal angiomyolipoma. Although almost all cases are benign, a relatively rare variant of epitheloid angiomyolipoma has got malignant potential and can even metastasize. Ultrasonography, CT and MRI scan are usually used for diagnosis of angiomyolipoma with high level of accuracy; even though some lesions may be confused as renal cell carcinoma on imaging studies. Here, a 48 year old man presented with a large intra-abdominal mass preoperatively diagnosed as a case of right renal cell carcinoma and radical nephrectomy was performed. Histopathology revealed epitheloid angiomyolipoma (EAML). PMID:27612907

  1. Familial renal cancer as an indicator of hereditary leiomyomatosis and renal cell cancer syndrome.

    PubMed

    Raymond, Victoria M; Herron, Casey M; Giordano, Thomas J; Gruber, Stephen B

    2012-03-01

    Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is a hereditary condition which typically presents with cutaneous and uterine leiomyomata. Papillary type II renal cell carcinoma and other less common histologic subtypes of renal cancer have been reported in HLRCC. We describe the case of a 31-year-old man in which the pathology review of his renal carcinoma and a positive family history of renal carcinoma allowed for the identification of a pathogenic mutation in the FH gene (c.698G>A;p.R233H) confirming the diagnosis of HLRCC. Recognition of this syndrome allowed for appropriate surveillance as well as identification of at-risk family members. Pathology review is essential for accurate diagnosis of a hereditary cancer syndrome in the setting of familial renal cancer. PMID:22127509

  2. Aqueous Extracts of Toona sinensis Leaves Inhibit Renal Carcinoma Cell Growth and Migration Through JAK2/stat3, Akt, MEK/ERK, and mTOR/HIF-2α Pathways.

    PubMed

    Chen, Yung-Chia; Chien, Ling-Hui; Huang, Bu-Miin; Chia, Yi-Chen; Chiu, Hui-Fen

    2016-01-01

    Toona sinensis (TS) is a type of deciduous tree, which is distributed widely in Asia and used as a traditional herb medicine. Previously, we demonstrated that aqueous extracts of TS leaves (TSL-1) induce apoptosis in two clear types of human renal carcinoma cells (ccRCC) via mitochondria-dependent pathway. In this study, we further investigated the more detailed mechanism of TSL-1-induced antitumor effects on ccRCCs. TSL-1 treatment arrested ccRCC cells in G0/G1 phase through the decrease of cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 as well as induction of p53 and FOXO3a protein expressions. On the other hand, the inhibitory effects of TSL-1 on migration were also observed in 786-O and A-498 cells. Mechanically, we presented that TSL-1 could suppress cell cycle progression and motility via inhibiting the phosphorylation of JAK2/stat3, Akt, MEK/ERK, and mTOR in a concentration- and time-dependent manner. Moreover, we found that TSL-1 inhibited p21, HIF-2α, c-Myc, VEGF, and MMP9 protein expressions in both cell lines. In conclusion, these findings suggested that TS-induced apoptosis and its antimigration activity in ccRCC cells were accompanied by inactivation of several oncogenic pathways. PMID:27115866

  3. ACR Appropriateness Criteria Renal Cell Carcinoma Staging.

    PubMed

    Vikram, Raghunandan; Beland, Michael D; Blaufox, M Donald; Moreno, Courtney Coursey; Gore, John L; Harvin, Howard J; Heilbrun, Marta E; Liauw, Stanley L; Nguyen, Paul L; Nikolaidis, Paul; Preminger, Glenn M; Purysko, Andrei S; Raman, Steven S; Taffel, Myles T; Wang, Zhen J; Weinfeld, Robert M; Remer, Erick M; Lockhart, Mark E

    2016-05-01

    Renal cell carcinoma accounts for 2%-3% of all visceral malignancies. Preoperative imaging can provide important staging and anatomic information to guide treatment decisions. Size of the primary tumor and degree of local invasion, such as involvement of perinephric fat or renal sinus fat, and tumor thrombus in renal veins and inferior vena cava are important detriments to local staging of primary tumor. Both kidneys are assessed for presence of other synchronous lesions. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and application by the panel of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:27016804

  4. Clear cell papillary renal cell carcinoma: a review.

    PubMed

    Kuroda, Naoto; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Furuya, Mitsuko; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Zhou, Ming; Petersson, Fredrik; López, José I; Hes, Ondrej; Michal, Michal; Amin, Mahul B

    2014-01-01

    The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type. PMID:25550767

  5. Renal cell cancer and exposure to gasoline: a review.

    PubMed Central

    McLaughlin, J K

    1993-01-01

    A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. PMID:8020434

  6. Synchronized renal tubular cell death involves ferroptosis

    PubMed Central

    Skouta, Rachid; Himmerkus, Nina; Mulay, Shrikant R.; Dewitz, Christin; De Zen, Federica; Prokai, Agnes; Zuchtriegel, Gabriele; Krombach, Fritz; Welz, Patrick-Simon; Weinlich, Ricardo; Vanden Berghe, Tom; Vandenabeele, Peter; Pasparakis, Manolis; Bleich, Markus; Weinberg, Joel M.; Reichel, Christoph A.; Bräsen, Jan Hinrich; Kunzendorf, Ulrich; Anders, Hans-Joachim; Stockwell, Brent R.; Green, Douglas R.; Krautwald, Stefan

    2014-01-01

    Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia–reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy. PMID:25385600

  7. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  8. Stem cells and progenitor cells in renal disease.

    PubMed

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

    2005-11-01

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

  9. Aldesleukin in advanced renal cell carcinoma.

    PubMed

    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

  10. Contemporary Treatment of Metastatic Renal Cell Carcinoma.

    PubMed

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y C

    2016-04-15

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  11. Contemporary Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y.C.

    2016-01-01

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  12. Protein Kinase RNA-Like Endoplasmic Reticulum Kinase-Mediated Bcl-2 Protein Phosphorylation Contributes to Evodiamine-Induced Apoptosis of Human Renal Cell Carcinoma Cells

    PubMed Central

    Wu, Wen-Shin; Chien, Chih-Chiang; Chen, Yen-Chou; Chiu, Wen-Ta

    2016-01-01

    We investigated the anticancer mechanism of evodiamine (EVO) against the viability of human A498 renal cell carcinoma (RCC) cells in vitro and in vivo. The in vitro study showed that EVO decreased the viability of A498 cells with the occurrence of apoptotic characteristics such as hypodiploid cells, DNA ladders, chromatin-condensed cells, and cleaved caspase (Casp)-3/poly(ADP ribose) polymerase (PARP) proteins. Pharmacological studies using chemical inhibitors of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) indicated that phosphorylation of the c-Jun N-terminal kinase (JNK) protein participated in EVO-induced cell death of A498 cells, and application of the JNK inhibitor, SP600125 (SP), inhibited EVO-induced cleavage of the Casp-3/PARP proteins and chromatin condensation according to Giemsa staining. EVO disruption of the mitochondrial membrane potential (MMP) with increased protein levels of the phosphorylated Bcl-2 protein (p-Bcl-2) was prevented by JNK inhibitors in A498 cells. A structure-activity relationship study showed that a methyl group at position 14 in EVO was important for its apoptotic effects and increased p-Bcl-2 protein in A498 cells. Furthermore, significant increases in the phosphorylated endoplasmic reticular stress protein, protein kinase RNA-like endoplasmic reticulum kinase (p-PERK at Thr980), by EVO were detected in A498 cells, and the PERK inhibitor, GSK2606414, significantly suppressed EVO-induced apoptosis, p-JNK, p-PERK, and cleaved PARP proteins. The in vivo study showed that EVO significantly reduced RCC growth elicited by a subcutaneous injection of A498 cells, and an increased protein level of p-PERK was observed according to an immunohistochemical analysis. Apoptosis by EVO was also demonstrated in other RCC cells such as 786-O, ACHN, and Caki-1 cells. This is the first study to demonstrate the anti-RCC effect of EVO via apoptosis in vitro and in vivo, and activation of JNK and PERK to induce Bcl-2

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

    ClinicalTrials.gov

    2016-09-07

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

  14. Renal veins and venous extension in clear cell renal cell carcinoma.

    PubMed

    Bonsib, Stephen M

    2007-01-01

    The 2002 TNM formulation defines a pT3b tumor as one that 'extends into the renal vein or its segmental (muscle containing) branches.' This definition elicits uncertainty when veins with little muscle are involved or the relationship to the main renal vein is unknown. The diameter and medial thickness of 10 normal renal venous systems were studied and compared to sinus veins involved in 54 pT3b clear cell renal cell carcinomas (CC). All tumors were grossly examined and sampled for histology by the author. An immunoperoxidase cocktail containing CD 31 and actin, Masson trichrome and elastic stains were employed to aid identification of intravenous tumor. The venous dissections showed variable numbers of primary and secondary divisions with substantial overlap in diameter and medial thickness. The medial thickness decreased with each proximal division and ranged from being nonexistent to being thick. Study of the 54 pT3b CC revealed that the initial phase of extrarenal extension involved large caliber veins draining the primary tumor. With extensive venous involvement, tumor invaded through the vein wall into sinus fat or demonstrated retrograde venous extension into adjacent cortex. Correlation between gross and histology revealed that most nodules of tumor within the sinus fat contained evidence of pre-existing veins. The following observations were made: (1) the diameter of a sinus vein or the quantity of muscle is a poor indicator of vein segment or relationship to the main renal vein; therefore, the wording used to define pT3b should be clarified; (2) extrarenal spread in CC begins with intravenous extension whereas sinus fat invasion is usually secondary; (3) retrograde venous extension occurs in cases with massive renal vein involvement; and (4) nodules within the sinus fat usually represent venous involvement. PMID:17170742

  15. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids

    PubMed Central

    Batchelder, Cynthia A.; Martinez, Michele L.; Duru, Nadire; Meyers, Frederick J.; Tarantal, Alice F.

    2015-01-01

    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. PMID:26317980

  16. Wnt Signaling in Renal Cell Carcinoma.

    PubMed

    Xu, Qi; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

    2016-01-01

    Renal cell carcinoma (RCC) accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers. PMID:27322325

  17. Wnt Signaling in Renal Cell Carcinoma

    PubMed Central

    Xu, Qi; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

    2016-01-01

    Renal cell carcinoma (RCC) accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers. PMID:27322325

  18. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma

    PubMed Central

    KUROZUMI, AKIRA; KATO, MAYUKO; GOTO, YUSUKE; MATSUSHITA, RYOSUKE; NISHIKAWA, RIKA; OKATO, ATSUSHI; FUKUMOTO, ICHIRO; ICHIKAWA, TOMOHIKO; SEKI, NAOHIKO

    2016-01-01

    Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis. PMID:26983694

  19. Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma.

    PubMed

    Kurozumi, Akira; Kato, Mayuko; Goto, Yusuke; Matsushita, Ryosuke; Nishikawa, Rika; Okato, Atsushi; Fukumoto, Ichiro; Ichikawa, Tomohiko; Seki, Naohiko

    2016-05-01

    Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis. PMID:26983694

  20. Genomic Heterogeneity of Translocation Renal Cell Carcinoma

    PubMed Central

    Couturier, Jérôme; Molinié, Vincent; Escudier, Bernard; Camparo, Philippe; Su, Xiaoping; Yao, Hui; Tamboli, Pheroze; Lopez-Terrada, Dolores; Picken, Maria; Garcia, Marileila; Multani, Asha S.; Pathak, Sen; Wood, Christopher G.; Tannir, Nizar M.

    2013-01-01

    Purpose Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity. Experimental design Cytogenomic analysis was performed with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and 4 cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was performed on 27 cases using pyrosequencing. Results tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in 7 tumors (44%), followed by a 9p loss in 6 cases (37%). Less frequent were losses of 3p and 17p in 5 cases (31%) each. Patients with 17q gain were older (P = 0.0006), displayed more genetic alterations (P < 0.003) and had a worse outcome (P = 0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell-line based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared to tumors from young patients (71.1% vs. 76.7%, P = 0.02). Conclusions Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology. PMID:23817689

  1. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    PubMed Central

    Mehrtens, Sarah; Veitch, David; Kulakov, Elizabeth; Perrett, Conal M.

    2016-01-01

    A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas). Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management. PMID:27144040

  2. Quiz. Correct answer to the quiz. Check your diagnosis. Clear cell papillary renal cell carcinoma.

    PubMed

    Joseph, Keva; Liu, Kai-Wen; Chang, I-Wei

    2015-06-01

    We incidentally observed a case of clear cell papillary renal cell carcinoma of an 81-year-old woman, presenting with intermittent left flank pain. It is a recently described rare renal parenchymal tumor. PMID:26328282

  3. Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment.

    PubMed

    Menko, Fred H; Maher, Eamonn R; Schmidt, Laura S; Middelton, Lindsay A; Aittomäki, Kristiina; Tomlinson, Ian; Richard, Stéphane; Linehan, W Marston

    2014-12-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene which inactivate the enzyme and alters the function of the tricarboxylic acid (Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The lifetime renal cancer risk for FH mutation carriers is estimated to be 15 %. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10-20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts of families. PMID:25012257

  4. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Renal cancer risk, surveillance and treatment

    PubMed Central

    Menko, Fred H.; Maher, Eamonn; Schmidt, Laura S.; Middelton, Lindsay A.; Aittomäki, Kristiina; Tomlinson, Ian; Richard, Stéphane; Linehan, W. Marston

    2015-01-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene, which inactivates the enzyme and alters the function of the tricarboxylic acid (TCA/ Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The estimated lifetime renal cancer risk for FH mutation carriers is estimated to be 15%. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10-20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts of families. PMID:25012257

  5. Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer?

    PubMed

    Semeniuk-Wojtaś, Aleksandra; Stec, Rafał; Szczylik, Cezary

    2016-05-01

    Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer. PMID:26850779

  6. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  7. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    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

  8. Renal cell carcinoma: links and risks

    PubMed Central

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

    2016-01-01

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

  9. Renal cell carcinoma: links and risks.

    PubMed

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

    2016-01-01

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

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

    PubMed

    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

  11. Metabolic alterations in renal cell carcinoma.

    PubMed

    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. PMID:26169313

  12. Clear cell papillary renal cell carcinoma is the fourth most common histologic type of renal cell carcinoma in 290 consecutive nephrectomies for renal cell carcinoma.

    PubMed

    Zhou, Haijun; Zheng, Shaojiang; Truong, Luan D; Ro, Jae Y; Ayala, Alberto G; Shen, Steven S

    2014-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) has recently been recognized as a distinct subtype of renal cell carcinoma (RCC) due to its unique morphologic, immunohistochemical, and genetic features and indolent clinical behavior. However, the incidence of this tumor in a nephrectomy series for renal mass has not been fully investigated. Twelve cases of CCP-RCC were identified from a total of 290 consecutive partial (n = 137) or radical nephrectomies (n = 153) for RCC from 2010 to 2012 in our hospital. In this series, CCP-RCC was the fourth most common (4.1%) kidney tumor following clear cell (conventional) (70%), papillary (16.6%), and chromophobe (5.9%) RCCs. The average age of the CCP-RCC patients was 58.2 years (range, 18-81 years), with an equal sex distribution. Four cases (33.3%) were associated with end-stage renal disease. Of the 12 CCP-RCCs, 9 presented as solitary tumors; 2 coexisted with clear cell RCC; and 1 with papillary RCC. The average size of tumors was 2.5 cm (range, 0.8-6.0 cm). All tumors were pT1 (10 pT1a and 2 pT1b). Two cases were initially misclassified as clear cell RCC. Strong positive cytokeratin 7 stain and negative stains with α-methylacyl-CoA racemase and RCC marker differentiate CCP-RCC from low-grade clear cell RCC with similar histologic features. We conclude that CCP-RCC is a common renal neoplastic entity, representing the fourth most common (4.1%) RCC. It can be easily misclassified due to its overlapping features with low-grade clear cell RCC. In equivocal cases, immunohistochemical stains with a small panel of markers (cytokeratin 7, α-methylacyl-CoA racemase, RCC marker, or CD10) are warranted in making the correct histologic classification. PMID:24182559

  13. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a rapid autopsy report of metastatic renal cell carcinoma.

    PubMed

    Udager, Aaron M; Alva, Ajjai; Chen, Ying-Bei; Siddiqui, Javed; Lagstein, Amir; Tickoo, Satish K; Reuter, Victor E; Chinnaiyian, Arul M; Mehra, Rohit

    2014-04-01

    Rapid ("warm") autopsies of patients with advanced metastatic cancer provide invaluable insight into the natural history, pathobiology, and morphology of advanced and treatment-resistant tumors. Here, we report a rapid autopsy case of a hereditary leiomyomatosis and renal cell carcinoma (HLRCC) patient with advanced metastatic renal cell carcinoma (RCC)-the first such case described for either a primary renal tumor or HLRCC-related cancer. Mutations in the fumarate hydratase (FH) gene underlie HLRCC, a rare syndrome involving cutaneous and uterine leiomyomata and aggressive kidney tumors. Loss of heterozygosity at the wild-type FH gene locus results in profound cellular metabolic derangement, "pseudohypoxic" upregulation of hypoxia-inducible factor 1α (HIF-1α)-dependent transcription, and aberrant protein succination; these molecular changes drive oncogenesis of kidney tumors in HLRCC patients. The current index patient had a high-grade RCC with classic morphologic features of HLRCC, including large nuclei with prominent eosinophilic nucleoli and perinucleolar clearing. In addition, this patient's RCC demonstrated extensive sarcomatoid and rhabdoid features-morphologies not previously well described in HLRCC-associated kidney tumors. Here, we report the extent of metastatic dissemination and supplement this unique tumor morphology with mitochondrial enzyme histochemistry and extended immunohistochemical analysis. Tumor cells strongly expressed PAX8, vimentin, CD10, and the HIF target GLUT1 and showed increased nuclear p53 accumulation; the expression of other RCC markers was negative. We also detail microscopic tubular epithelial changes in the grossly uninvolved ipsilateral renal parenchyma and demonstrate sporadic, aberrant upregulation of the HIF targets GLUT1 and CAIX in dysplastic peritumoral tubules. PMID:24625422

  14. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a rapid autopsy report of metastatic renal cell carcinoma

    PubMed Central

    Udager, Aaron M.; Alva, Ajjai; Chen, Ying-Bei; Siddiqui, Javed; Lagstein, Amir; Tickoo, Satish K.; Reuter, Victor E.; Chinnaiyian, Arul M.; Mehra, Rohit

    2014-01-01

    Rapid (“warm”) autopsies of patients with advanced metastatic cancer provide invaluable insight into the natural history, pathobiology, and morphology of advanced and treatment-resistant tumors. Here, we report a rapid autopsy case of a hereditary leiomyomatosis and renal cell carcinoma (HLRCC) patient with advanced metastatic renal cell carcinoma (RCC)—the first such case described for either a primary renal tumor or HLRCC-related cancer. Mutations in the fumarate hydratase (FH) gene underlie HLRCC, a rare syndrome involving cutaneous and uterine leiomyomata and aggressive kidney tumors. Loss of heterozygosity at the wild-type FH gene locus results in profound cellular metabolic derangement, “pseudohypoxic” upregulation of hypoxia-inducible factor 1[alpha] (HIF-1[alpha])-dependent transcription, and aberrant protein succination; these molecular changes drive oncogenesis of kidney tumors in HLRCC patients. The current index patient had a high-grade RCC with classic morphologic features of HLRCC, including large nuclei with prominent eosinophilic nucleoli and perinucleolar clearing. In addition, this patient’s RCC demonstrated extensive sarcomatoid and rhabdoid features—morphologies not previously well described in HLRCC-associated kidney tumors. Here, we report the extent of metastatic dissemination and supplement this unique tumor morphology with mitochondrial enzyme histochemistry and extended immunohistochemical analysis. Tumor cells strongly expressed PAX8, vimentin, CD10, and the HIF target GLUT1 and showed increased nuclear p53 accumulation; the expression of other RCC markers was negative. We also detail microscopic tubular epithelial changes in the grossly uninvolved ipsilateral renal parenchyma and demonstrate sporadic, aberrant upregulation of the HIF targets GLUT1 and CAIX in dysplastic peritumoral tubules. PMID:24625422

  15. Heart failure as the first manifestation of renal cell carcinoma

    PubMed Central

    Lee, Chee Meng; Kurugulasigamoney, Gunasegaran; Ng, Lay Guat

    2015-01-01

    We report the rare case of a patient with advanced renal cell carcinoma (RCC) who initially presented to the hospital with symptoms of cardiac failure. Preoperative cardiac studies did not reveal any underlying ischemia. After resection of a large 14-cm left renal tumor, cardiac function was noted to improve dramatically. We discuss this case of concomitant RCC and nonischemic cardiomyopathy. PMID:25598941

  16. Epidemiologic characteristics and risk factors for renal cell cancer

    PubMed Central

    Lipworth, Loren; Tarone, Robert E; Lund, Lars; McLaughlin, Joseph K

    2009-01-01

    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, including evaluation of gene–environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer. PMID:20865085

  17. Bone Metastasis from Renal Cell Carcinoma

    PubMed Central

    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

  18. Two papillary renal cell carcinomas of different origin following renal transplantation (Case report).

    PubMed

    Gerth, Hans-Ulrich; Pohlen, Michele; Thoennissen, Nils-Heinrich; Suwelack, Barbara; Pavenstädt, Hermann-Josef; Störkel, Stefan; Abbas, Mahmoud; Spieker, Tilmann; Thölking, Gerold

    2012-07-01

    Papillary renal cell carcinoma (PRCC) is a rare malignant tumor entity compared to common clear cell renal carcinoma. In the present study, we report a patient who was diagnosed with PRCC twice and successfully treated each time following renal transplantation. The first PRCC was located in the left native kidney two years following transplantation, and the second PRCC was diagnosed in the allograft 13 years following transplantation. The two tumors were completely removed by surgery in stage I of the disease with sufficient conservation of the allograft function. Notably, the tumors had a different origin as indicated by the microsatellite analysis, which reflects the exceptional course of the case. Risk factors for PRCC were identified in our patient. We concluded that high-risk candidates for malignancies in renal transplant recipients should receive shorter ultrasonic screening intervals, which may facilitate early tumor detection and improve outcome rates. PMID:22807965

  19. Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis.

    PubMed Central

    Bugert, P.; Kovacs, G.

    1996-01-01

    Recent application of molecular cytogenetic techniques has resulted in a new type of genetic classification of renal cell tumors. The key aspect of the novel diagnostic concept is reflected by biologically distinct entities, each characterized by a specific combination of genetic changes. To work out a diagnostic/prognostic approach, we have applied polymorphic microsatellite markers for a quick analysis, based on polymerase chain reaction, of 82 tumor specimens. We compared the results to previously evaluated cytogenetic and histological data. All nonpapillary and chromophobe renal cell carcinomas, which make up approximately 90% of all malignant renal cell tumors, and a subset of renal oncocytomas were correctly diagnosed by detection of loss of heterozygosity at chromosomal sites 1, 2, and 3p. Allelic losses at chromosomal regions 8p, 9p, and 14q are associated with an advanced pathological stage of nonpapillary renal cell carcinomas. A loss of heterozygosity at chromosomes 6, 10, 13, 17, and 21, in addition to those at chromosomes 1 and 2, confirm the diagnosis of chromophobe renal cell tumors. Using this approach, the differential diagnosis of renal cell tumors could be carried out within 1 or 2 days. Images Figure 2 PMID:8952540

  20. A patient with Multiple myeloma and Renal cell carcinoma

    PubMed Central

    Shahi, Farhad; Ghalamkari, Marziye; Mirzania, Mehrzad; Khatuni, Mahdi

    2016-01-01

    The coexistence of two malignancies is rarely seen. A little association between hematologic malignancies especially multiple myeloma and renal cell carcinoma has been reported in the recent past. Several case series revealed a bidirectional association between these two malignancies which may be due to the common risk factors, similar cytokine growth requirements and clinical presentation. Here, we aim to describe a patient who had multiple myeloma and in his work up renal cell carcinoma was found out incidentally. We would like to create awareness among clinicians for the coincidence of Renal cell carcinoma and Multiple myeloma. PMID:27047652

  1. Metastatic chromophobe renal cell carcinoma to the brain.

    PubMed

    Prayson, Richard A

    2016-04-01

    Metastases represent the most common tumors of the central nervous system, with clear cell renal cell carcinomas showing a particular predilection to involve the brain. This report documents an unusual case of a patient with a chromophobe renal cell carcinoma presenting with a brain metastasis. A 58-year-old man presented with stroke-like symptomatology, including expressive aphasia, right side facial weakness, headaches and vomiting. CT imaging demonstrated a 4.7 cm left frontal lobe hemorrhagic mass. He underwent surgery with excision of the mass, which was marked by sheets of large cells with lightly eosinophilic to clear cytoplasm. PAX8 staining was positive and a diagnosis of clear cell carcinoma of probably renal origin was rendered. Subsequently, CT imaging of the abdomen revealed a 12.9 cm left renal mass. The patient underwent a left nephrectomy and a diagnosis of chromophobe renal cell carcinoma was made. The tumor was noted to extend into the perirenal fat and to have involved a paraaortic lymph node. Re-review of the frontal lobe lesion confirmed the tumor was the same. Chromophobe renal cell carcinomas are far less common than clear cell tumors, are less likely to metastasize, and generally have a more favorable overall prognosis. When they metastasize, they most commonly involve the liver, lung and lymph nodes, in contrast to the more common clear cell carcinomas that typically spread to the lungs, bone and brain. PMID:26589090

  2. A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona.

    PubMed

    Ho, Thai H; Nateras, Rafael Nunez; Yan, Huihuang; Park, Jin G; Jensen, Sally; Borges, Chad; Lee, Jeong Heon; Champion, Mia D; Tibes, Raoul; Bryce, Alan H; Carballido, Estrella M; Todd, Mark A; Joseph, Richard W; Wong, William W; Parker, Alexander S; Stanton, Melissa L; Castle, Erik P

    2015-01-01

    To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25 °C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes. PMID

  3. A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona

    PubMed Central

    Ho, Thai H.; Nateras, Rafael Nunez; Yan, Huihuang; Park, Jin G.; Jensen, Sally; Borges, Chad; Lee, Jeong Heon; Champion, Mia D.; Tibes, Raoul; Bryce, Alan H.; Carballido, Estrella M.; Todd, Mark A.; Joseph, Richard W.; Wong, William W.; Parker, Alexander S.; Stanton, Melissa L.; Castle, Erik P.

    2015-01-01

    To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes. PMID

  4. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  5. Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients.

    PubMed

    Baraldi, Olga; Grandinetti, Valeria; Donati, Gabriele; Comai, Giorgia; Battaglino, Giuseppe; Cuna, Vania; Capelli, Irene; Sala, Elisa; La Manna, Gaetano

    2016-01-01

    Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20-30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias. PMID:26160700

  6. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.

    PubMed

    Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R; Voicu, Horatiu; Torres-Garcia, Wandaliz; Verhaak, Roel G W; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan

    2015-10-01

    Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the

  7. Renal cell carcinoma arising in ipsilateral duplex system.

    PubMed

    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

  8. Occupation and renal cell cancer in Central and Eastern Europe

    PubMed Central

    Heck, Julia E; Charbotel, Barbara; Moore, Lee E; Karami, Sara; Zaridze, David G; Matveev, Vsevolod; Janout, Vladimir; Kollárová, Helena; Foretova, Lenka; Bencko, Vladimir; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Mates, Dana; Ferro, Gilles; Chow, Wong-Ho; Rothman, Nathaniel; Stewart, Patricia; Brennan, Paul; Boffetta, Paolo

    2010-01-01

    Objective Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer etiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. Methods From 1999–2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (OR) and 95% confidence intervals (CI) of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. Results A total of 992 histologically confirmed incident renal cell cancer cases and 1,465 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labor and animal husbandry (OR=1.43, 95% CI 1.05, 1.93), particularly among women employed as general farm workers (OR=2.73, 95% CI 1.05, 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR=1.89, 95% CI 1.35, 2.65), and mechanical engineers (OR=1.71, 95% CI 1.03, 2.84). Conclusions Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers. PMID:19737732

  9. A Bioartificial Renal Tubule Device Embedding Human Renal Stem/Progenitor Cells

    PubMed Central

    Sciancalepore, Anna Giovanna; Sallustio, Fabio; Girardo, Salvatore; Gioia Passione, Laura; Camposeo, Andrea; Mele, Elisa; Di Lorenzo, Mirella; Costantino, Vincenzo; Schena, Francesco Paolo; Pisignano, Dario

    2014-01-01

    We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs) was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na+K+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5)% and (13±5)%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative “lab-on-a-chip” platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses. PMID:24498117

  10. Perfusion computed tomography in renal cell carcinoma.

    PubMed

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

    2015-07-28

    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 (pCT), goes down to the molecular level and provides new perspectives in imaging of RCC. pCT 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 pCT 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 pCT in staging and response assessment in patients with RCCs. PMID:26217456

  11. Systemic adjuvant therapies in renal cell carcinoma.

    PubMed

    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

  12. Transport of circulating serum cholesterol by human renal cell carcinoma

    SciTech Connect

    Clayman, R.V.; Figenshau, R.S.; Prigge, W.F.; Forstrom, L.; Gebhard, R.L.

    1987-06-01

    Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected /sup 131/I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. /sup 131/I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded /sup 131/I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer.

  13. Renal erythropoietin-producing cells in health and disease

    PubMed Central

    Souma, Tomokazu; Suzuki, Norio; Yamamoto, Masayuki

    2015-01-01

    Erythropoietin (Epo) is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs). Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are the major source of scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory cytokines. Notably, myofibroblast-transformed REPs (MF-REPs) recover their original physiological properties after resolution of the disease insults, suggesting that renal anemia and fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted therapeutics for both renal fibrosis and anemia. This review summarizes the regulatory mechanisms how hypoxia-inducible Epo gene expression is attained in health and disease conditions. PMID:26089800

  14. A tale of two cancers: Complete genetic analysis of chromophobe renal cell carcinoma contrasts with clear cell renal cell carcinoma

    PubMed Central

    Fahey, Catherine C; Rathmell, W Kimryn

    2015-01-01

    The Cancer Genome Atlas undertook a comprehensive genetic analysis of chromophobe renal cell carcinoma, the first of the rare tumor types to be analyzed. This analysis identified the putative region of origin as the distal nephron. Alterations in mitochondrial function, mtDNA mutations, and recurrent structural rearrangements within the TERT promoter region were also identified. PMID:27308442

  15. Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.

    PubMed

    Williamson, Sean R; Gupta, Nilesh S; Eble, John N; Rogers, Craig G; Michalowski, Susan; Zhang, Shaobo; Wang, Mingsheng; Grignon, David J; Cheng, Liang

    2015-11-01

    Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR. PMID:26457355

  16. Renal cell carcinoma arising in a regressed multicystic dysplastic kidney.

    PubMed

    Rackley, R R; Angermeier, K W; Levin, H; Pontes, J E; Kay, R

    1994-11-01

    Controversy surrounds the management of multicystic dysplastic kidney. Recent advances in radiological imaging have resulted in a higher incidence of its detection, and they provide an accurate noninvasive means of diagnosis and followup. Consequently, the need for surgical removal of these lesions is being reevaluated. We report a case of renal cell carcinoma arising from solid renal dysplasia associated with a regressed multicystic dysplastic kidney. We emphasize the potential risk of nonoperative management of these lesions and further define the spectrum of malignant degeneration associated with renal dysplasia. PMID:7933196

  17. Targeting both IGF-1R and mTOR synergistically inhibits growth of renal cell carcinoma in vitro

    PubMed Central

    2013-01-01

    Background Advanced or metastatic renal cell carcinoma (RCC) has a poor prognosis, because it is relatively resistant to conventional chemotherapy or radiotherapy. Treatments with human interferon-α2b alone or in combination with mammalian target of rapamycin (mTOR) inhibitors have led to only a modest improvement in clinical outcome. One observation made with mTOR inhibitors is that carcinomas can overcome these inhibitory effects by activating the insulin-like growth factor-I (IGF-I) signaling pathway. Clinically, there is an association of IGF-I receptor (IGF-IR) expression in RCC and poor long-term patient survival. We have developed a humanized anti-IGF-IR monoclonal antibody, hR1, which binds to RCC, resulting in effective down-regulation of IGF-IR and moderate inhibition of cell proliferation in vitro. In this work, we evaluate the anti-tumor activity of two novel IGF-1R-targeting agents against renal cell carcinoma given alone or in combination with an mTOR inhibitor. Methods hR1 was linked by the DOCK-AND-LOCK™ (DNL™) method to four Fabs of hR1, generating Hex-hR1, or to four molecules of interferon-α2b, generating 1R-2b. Eight human RCC cell lines were screened for IGF-1R expression and sensitivity to treatment with hR1 in vitro. Synergy with an mTOR inhibitor, temsirolimus, was tested in a cell line (ACHN) with low sensitivity to hR1. Results Hex-hR1 induced the down-regulation of IGF-IR at 10-fold lower concentrations compared to the parental hR1. Sensitivity to growth inhibition mediated by hR1 and Hex-hR1 treatments correlated with IGF-1R expression (higher expression was more sensitive). The potency of 1R-2b to inhibit the in vitro growth of RCC was also demonstrated in two human cell lines, ACHN and 786-O, with EC50–values of 63 and 48 pM, respectively. When combined with temsirolimus, a synergistic growth-inhibition with hR1, Hex-hR1, and 1R-2b was observed in ACHN cells at concentrations as low as 10 nM for hR1, 1 nM for Hex-hR1, and 2.6 n

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

    PubMed

    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

  19. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    PubMed

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

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  20. Acute Kidney Injury Associated with Renal Cell Carcinoma Complicated by Renal Vein and Inferior Vena Cava Involvement.

    PubMed

    Sugase, Taro; Akimoto, Tetsu; Kubo, Taro; Imai, Toshimi; Otani-Takei, Naoko; Miki, Takuya; Takeda, Shin-Ichi; Nukui, Akinori; Muto, Shigeaki; Morita, Tatsuo; Nagata, Daisuke

    2016-01-01

    Acute kidney injury (AKI) is caused by diverse pathologies, although it may occasionally result from concurrent renal efflux disturbances. We herein describe a case of AKI in a patient complicated by renal cell carcinoma (RCC) with renal vein and inferior vena cava (IVC) involvement. A neoplastic thrombus which disrupted the blood flow in the renal vein appeared to play a role in the rapid decline in the renal function. Such a scenario has rarely been mentioned in the previous literature describing the cases of RCC complicated by AKI. Concerns regarding the diagnostic and therapeutic strategies for RCC are also discussed. PMID:27580548

  1. Renal epithelial cells can release ATP by vesicular fusion

    PubMed Central

    Bjaelde, Randi G.; Arnadottir, Sigrid S.; Overgaard, Morten T.; Leipziger, Jens; Praetorius, Helle A.

    2013-01-01

    Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30), which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1) cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin) reduced both the spontaneous and hypotonically (80%)-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1) and vesicular transport (nocodazole). These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ~90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP) or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50%) or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8 and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells. PMID:24065923

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

    PubMed

    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

  3. An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

    PubMed

    Hakimi, A Ari; Reznik, Ed; Lee, Chung-Han; Creighton, Chad J; Brannon, A Rose; Luna, Augustin; Aksoy, B Arman; Liu, Eric Minwei; Shen, Ronglai; Lee, William; Chen, Yang; Stirdivant, Steve M; Russo, Paul; Chen, Ying-Bei; Tickoo, Satish K; Reuter, Victor E; Cheng, Emily H; Sander, Chris; Hsieh, James J

    2016-01-11

    Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort. PMID:26766592

  4. Oligoarray comparative genomic hybridization of renal cell tumors that developed in patients with acquired cystic renal disease.

    PubMed

    Kuntz, Eva; Yusenko, Maria V; Nagy, Anetta; Kovacs, Gyula

    2010-09-01

    Renal cell carcinoma occurs at higher frequency in acquired cystic renal disease than in the general population. We have analyzed 4 tumors obtained from the kidneys of 2 patients with acquired cystic renal disease, including 2 conventional renal cell carcinomas and 2 acquired cystic renal disease-associated tumors, for genetic alterations. DNA changes were established by applying the 44K Agilent Oligonucleotide Array-Based CGH (Agilent Technologies, Waldbronn, Germany), and mutation of VHL gene was detected by direct sequencing of the tumor genome. DNA losses and mutation of the VHL gene, which are characteristic for conventional renal cell carcinomas, were seen in 2 of the tumors. The acquired cystic renal disease-associated eosinophilic-vacuolated cell tumor showed gain of chromosomes 3 and 16. No DNA alterations occurred in the papillary clear cell tumor. We suggest that not only the morphology but also the genetics of renal cell tumors associated with acquired cystic renal disease may differ from those occurring in the general population. PMID:20646738

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

    PubMed

    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

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

    PubMed Central

    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

  7. Renal Neoplasms With Overlapping Features of Clear Cell Renal Cell Carcinoma and Clear Cell Papillary Renal Cell Carcinoma: A Clinicopathologic Study of 37 Cases From a Single Institution.

    PubMed

    Dhakal, Hari P; McKenney, Jesse K; Khor, Li Yan; Reynolds, Jordan P; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-02-01

    Clear cell papillary renal cell carcinoma (CCPRCC) was recently included in the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia as a subtype of RCC that is morphologically, immunohistochemically, and genetically distinct from both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma. In our clinical practice we have observed tumors with overlapping histologic features of CCPRCC and CCRCC; therefore, our aim was to describe the morphologic, immunohistochemical, and clinical characteristics of these tumors. We examined a large series of consecutive nephrectomies diagnosed as CCRCC and found 37 tumors with morphologic overlap between CCRCC and CCPRCC, identifying 2 patterns. Pattern 1 tumors (N=19) had areas diagnosable as CCRCC admixed with foci having a prominent linear arrangement of nuclei away from the basement membrane imparting a resemblance to CCPRCC; however, other morphologic features commonly seen in CCPRCC (such as branching acini and cystic spaces with papillary tufts) were not typical and, when present, were focal or poorly developed. Pattern 2 (N=18) tumors had 2 discrete areas, one area with an appearance strongly resembling CCPRCC and the other with higher grade nuclei and features diagnosable as CCRCC, sometimes including rhabdoid differentiation, sarcomatoid differentiation, necrosis, and high-stage disease. Four (21%) of the pattern 1 tumors had grade 3 nuclei in the CCRCC-like areas, and 4 were high stage (pT3a). Of the 16 immunostained pattern 1 tumors, all expressed cytokeratin 7 (CK7) at least focally in the CCPRCC-like areas, strongly and diffusely in 9 (56%) cases; 12 (75%) showed negative to focal and/or weak CK7 expression in the CCRCC-like areas. CD10, α-methylacyl-CoA-racemase, high-molecular-weight cytokeratin, and carbonic anhydrase IX (CA IX) had no significant differential expression between these foci. No cup-like staining pattern was seen with CA IX. Two (11%) patients

  8. Experimental depletion of different renal interstitial cell populations

    SciTech Connect

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

    1988-04-01

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

  9. Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

    PubMed

    Diolombi, Mairo L; Cheng, Liang; Argani, Pedram; Epstein, Jonathan I

    2015-12-01

    There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients' ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients having no evidence of

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

    PubMed Central

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G.H.

    2016-01-01

    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 selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- 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. PMID:27141211

  11. The spectrum of renal cell carcinoma in adults.

    PubMed

    Ananthakrishnan, Lakshmi; Kapur, Payal; Leyendecker, John R

    2016-06-01

    The spectrum of renal cell carcinoma (RCC) includes many neoplasms with distinct cytogenetics, biologic behaviors, and imaging appearances. The advent of molecular therapies targeting different tumor types, new insights into the relative roles of biopsy and surveillance for small incidental tumors, and a growing array of nephron-sparing interventions have altered management of RCC. Similarly, the role of the radiologist is changing, and it is becoming increasingly important for radiologists to familiarize themselves with the various types of RCC. This article introduces the reader to the common and uncommon recognized types of renal cell carcinoma and discusses how these neoplasms differ in imaging appearance and behavior. PMID:27108133

  12. Metastatic Renal Cell Carcinoma to the Oral Cavity.

    PubMed

    Guimarães, Douglas Magno; Pontes, Flavia Sirotheau Correa; Miyahara, Ligia Akiko Ninokata; Guerreiro, Marcella Yasmin Reis; de Almeida, Maria Clara Lopes; Pontes, Helder Antonio Rebelo; Pinto, Decio Dos Santos

    2016-09-01

    Metastases to the oral cavity are extremely rare events, representing less than 1% of all malignant oral tumors. Renal cell carcinoma constitutes about 3% of solid tumors in adults, and it is the most frequent kidney neoplasm, representing about 90% of kidney malignancies. Due to the silent growth of this neoplasm, most patients have no symptoms and the diagnosis is belated, usually after metastases. The present study reports an additional patient of metastatic renal cell carcinoma to the oral cavity regarding the clinical and pathologic features. PMID:27607131

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

    PubMed

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

    2016-02-01

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

  14. MET Inhibition in Clear Cell Renal Cell Carcinoma

    PubMed Central

    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

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

    PubMed Central

    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

  16. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma

    PubMed Central

    Wu, Yan; Kwon, Young Suk; Labib, Mina; Foran, David J.; Singer, Eric A.

    2015-01-01

    As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC) continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI) now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma. PMID:26609190

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

    SciTech Connect

    Van der Hauwaert, Cynthia; Savary, Grégoire; Buob, David; Leroy, Xavier; Aubert, Sébastien; Flamand, Vincent; Hennino, Marie-Flore; Perrais, Michaël; 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.

  18. Renal cell carcinoma in a transplanted kidney: MR imaging findings.

    PubMed

    Leonardou, Polytimi; Semelka, Richard C; Mastropasqua, Maria; Kanematsu, Masayuki; Woosley, John T

    2003-07-01

    We report the MR findings of a 42-year-old man who developed renal cell carcinoma in an allograft kidney, 10 years after transplantation. The lower pole of the transplant kidney showed a solid lesion which was well shown on the post gadolinium fat suppressed images as a heterogeneously enhancing 2 cm mass lesion. PMID:12915202

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

    PubMed Central

    A, Sankin

    2016-01-01

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

  20. Dietary acrylamide and risk of renal cell cancer.

    PubMed

    Mucci, Lorelei A; Lindblad, Per; Steineck, Gunnar; Adami, Hans-Olov

    2004-05-01

    The detection of acrylamide, classified as a probable human carcinogen, in commonly consumed foods created public health alarm. Thus far, only 2 epidemiologic studies have examined the effect of dietary acrylamide on cancer risk. Presently, we reanalyzed data from a large population-based Swedish case-control study of renal cell cancer. Food frequency data were linked with national food databases on acrylamide content, and daily acrylamide intake was estimated for participants. The risk of renal cell cancer was evaluated for intake of food items with elevated acrylamide levels and for total daily acrylamide dose. Adjusting for potential confounders, there was no evidence that food items with elevated acrylamide, including coffee (OR(highest vs. lowest quartile) = 0.7; 95% CI = 0.4-1.1), crisp breads (OR(highest vs. lowest quartile) = 1.0; 95% CI = 0.6-1.6) and fried potatoes (OR(highest vs. lowest quartile) = 1.1; 95% CI = 0.7-1.7), were associated with a higher risk of renal cell cancer risk. Furthermore, there was no association between estimated daily acrylamide intake through diet and cancer risk (OR(highest vs. lowest quartile) = 1.1; 95% CI = 0.7-1.8; p for trend = 0.8). The results of this study are in line with the 2 previous studies examining dietary acrylamide and suggest there is no association between dietary acrylamide and risk of renal cell cancer. PMID:14999788

  1. Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma?

    PubMed

    Hes, Ondrej; Condom Mundo, Enric; Peckova, Kvetoslava; Lopez, Jose I; Martinek, Petr; Vanecek, Tomas; Falconieri, Giovanni; Agaimy, Abbas; Davidson, Whitney; Petersson, Fredrik; Bulimbasic, Stela; Damjanov, Ivan; Jimeno, Mireya; Ulamec, Monika; Podhola, Miroslav; Sperga, Maris; Pane Foix, Maria; Shelekhova, Ksenya; Kalusova, Kristyna; Hora, Milan; Rotterova, Pavla; Daum, Ondrej; Pivovarcikova, Kristyna; Michal, Michal

    2016-05-01

    Biphasic squamoid alveolar renal cell carcinoma (BSARCC) has been recently described as a distinct neoplasm. Twenty-one cases from 12 institutions were analyzed using routine histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization. Tumors were removed from 11 male and 10 female patients, whose age ranged from 53 to 79 years. The size of tumors ranged from 1.5 to 16 cm. Follow-up information was available for 14 patients (range, 1 to 96 mo), and metastatic spread was found in 5 cases. All tumors comprised 2 cell populations arranged in organoid structures: small, low-grade neoplastic cells with scant cytoplasm usually lining the inside of alveolar structures, and larger squamoid cells with more prominent cytoplasm and larger vesicular nuclei arranged in compact nests. In 9/21 tumors there was a visible transition from such solid and alveolar areas into papillary components. Areas composed of large squamoid cells comprised 10% to 80% of total tumor volume. Emperipolesis was present in all (21/21) tumors. Immunohistochemically, all cases were positive for cytokeratin 7, EMA, vimentin, and cyclin D1. aCGH (confirmed by fluorescence in situ hybridization) in 5 analyzable cases revealed multiple numerical chromosomal changes including gains of chromosomes 7 and 17 in all cases. These changes were further disclosed in 6 additional cases, which were unsuitable for aCGH. We conclude that tumors show a morphologic spectrum ranging from RCC with papillary architecture and large squamoid cells to fully developed BSARCC. Emperipolesis in squamoid cells was a constant finding. All BSARCCs expressed CK7, EMA, vimentin, and cyclin D1. Antibody to cyclin D1 showed a unique and previously not recognized pattern of immunohistochemical staining. Multiple chromosomal aberrations were identified in all analyzable cases including gains of chromosomes 7 and 17, indicating that they are akin to papillary RCC. Some BSARCCs were

  2. Circulating Tumor Cell Composition in Renal Cell Carcinoma

    PubMed Central

    Bublitz, Kira; Lazaridis, Lazaros; Goergens, André; Giebel, Bernd; Schuler, Martin; Hoffmann, Andreas-Claudius

    2016-01-01

    Purpose Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a “liquid biopsy” in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies. Experimental Design Peripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis. Results We detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC. Conclusions Patients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted. PMID:27101285

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

    Cancer.gov

    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.

  4. Renal squamous cell carcinoma mimicking xanthogranulomatous pyelonephritis: Case report and review of literature.

    PubMed

    Khoo, Hau Wei; Lee, Chau Hung

    2016-06-01

    Primary renal squamous cell carcinoma (SCC) is a rare primary malignancy of the kidney. Diagnosis is usually delayed because of its lack of characteristic clinical and imaging features and inherent aggressive nature. We present a case of primary renal SCC in a 66-year-old woman with bilateral renal calculi and a complex right lower pole renal mass. The diagnosis of primary renal SCC was established based on the histopathology after right nephrectomy. PMID:27257454

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

    PubMed

    Hu, J; Mao, Y; White, K

    2002-05-01

    This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females. PMID:12063361

  6. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

    PubMed Central

    2013-01-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

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

    PubMed

    Freedman, Benjamin S; Steinman, Theodore I

    2015-08-01

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

  8. [Renal urothelial carcinoma mainly composed of signet-ring cells].

    PubMed

    Povzun, S A; Guseva, E A; Konstantinova, A M; Shelekhova, K V

    2015-01-01

    Autopsy study of an 80-year-old man has identified his renal tumor metastasizing to the heart, lung, and liver as urothelial car- cinoma; at the same time some cells in the main tumor and all cells in the metastases had a signet-ring phenotype, but neither mucicarcimine nor alcian blue stained the cell cytoplasm. The paper provides the histological and immunohistochemical pattern of the tumor and emphasizes its exclusive rarity. Attention is drawn to the possibility of signet-ring cell transformation in the cells of different tumors, including nonepithelial ones. PMID:26841650

  9. Intratumoral Morphologic and Molecular Heterogeneity of Rhabdoid Renal Cell Carcinoma: Challenges for Personalized Therapy

    PubMed Central

    Singh, Rajesh R.; Murugan, Paari; Patel, Lalit R.; Voicu, Horatiu; Yoo, Suk-Young; Majewski, Tadeusz; Mehrotra, Meenakshi; Wani, Khalida; Tannir, Nizar; Karam, Jose A.; Jonasch, Eric; Wood, Christopher G.; Creighton, Chad J.; Medeiros, L. Jeffrey; Broaddus, Russell R.; Tamboli, Pheroze; Baggerly, Keith A.; Aldape, Kenneth D.; Czerniak, Bogdan; Luthra, Rajyalakshmi; Sircar, Kanishka

    2015-01-01

    Rhabdoid histology in clear cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear cell renal cell carcinoma. We macrodissected the rhabdoid and clear cell epithelioid components from 12 cases of rhabdoid clear cell renal cell carcinoma. We assessed cancer related mutations from 8 cases using a clinical next generation exome sequencing platform. The transcriptome of rhabdoid clear cell renal cell carcinoma (n=8) and non-rhabdoid clear cell renal cell carcinoma (n=37) was assessed by RNA-seq and gene expression microarray. VHL (63%) showed identical mutations in all regions from the same tumor. BAP1 (38%) and PBRM1 (13%) mutations were identified in the rhabdoid but not the epithelioid component and were mutually exclusive in 3/3 cases and 1 case, respectively. SETD2 (63%) mutations were discordant between different histologic regions in 2/5 cases, with mutations called only in the epithelioid and rhabdoid components, respectively. The transcriptome of rhabdoid clear cell renal cell carcinoma was distinct from advanced stage and high grade clear cell renal cell carcinoma. The diverse histologic components of rhabdoid clear cell renal cell carcinoma, however, showed a similar transcriptomic program, including a similar prognostic gene expression signature. Rhabdoid clear cell renal cell carcinoma is transcriptomically distinct and shows a high rate of SETD2 and BAP1 mutations and a low rate of PBRM1 mutations. Driver mutations in clear cell renal cell carcinoma are often discordant across different morphologic regions whereas the gene expression program is relatively stable. Molecular profiling of clear cell renal cell carcinoma may improve by assessing for gene expression and sampling tumor foci from different histologic

  10. A Case of Metastatic Renal Cell Carcinoma Mimicking Granuloma Pyogenicum

    PubMed Central

    Jin, Won Woo; Chung, Ji Min; Jung, Kyoung Eun; Park, Jong Wook

    2008-01-01

    Renal cell carcinoma (RCC) is well known for its frequent metastasis and particularly to the lungs, liver, bones and brain, but metastasis to the skin is rare. We report here on a case of metastatic RCC in a 73-year-old man who presented with a 1.5 cm sized, moist, beefy-red and exophytic nodule on the scalp. The lesion had grown rapidly for 2 months and it clinically mimicked granuloma pyogenicum. A skin biopsy revealed a solid mass composed of clear cells with clear cytoplasm and oval hyperchromatic nuclei, and they were arranged in an alveolar pattern. As skin metastasis from renal cell carcinoma signals widespread systemic metastasis and a poor prognosis, clinicians should conduct a careful inspection of the skin of a patient with RCC and they should also have a high index of suspicion for finding a primary internal organ malignancy in the RCC patients who present with a skin lesion. PMID:27303209

  11. Gastric metastasis of renal cell carcinoma 20 years after radical nephrectomy

    PubMed Central

    Akay, Ebru; Kala, Mehtap; Karaman, Hatice

    2016-01-01

    Renal cell carcinomas account for 2–3% of malignant neoplasms in adults. The lung, soft tissues and bone represent the most frequent sites of distant metastasis in renal cell carcinoma. Gastric metastasis is rare. Our case was a 72-year-old man with complaints of fatigue and loss of appetite. In history, he had unergone radical nephrectomy due to renal cell carcinoma in 1993. A polypoid lesion was observed in upper gastrointestinal endoscopy. Histopathology of gastric biopsy specimen was reported as renal cell carcinoma. In English literature, there are 50 cases diagnosed as gastric metastasis from renal cell carcinoma. To date, there are only 4 cases with extremely late gastric metastasis of renal cell carcinoma. Herein, we present a rare case which underwent radical nephrectomy due to renal cell carcinoma and found to have gastric metastasis at 20. year of his follow-up. PMID:27274897

  12. PARTIAL NEPHRECTOMY IN THE SETTING OF METASTATIC RENAL CELL CARCINOMA

    PubMed Central

    Babaian, Kara N.; Merrill, Megan M.; Matin, Surena; Tamboli, Pheroze; Tannir, Nizar M.; Jonasch, Eric; Wood, Christopher G.; Karam, Jose A.

    2015-01-01

    Purpose Cytoreductive nephrectomy (CN) remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma (mRCC). Although the role of partial nephrectomy (PN) is well accepted in patients with localized disease, limited data are available regarding PN in the metastatic setting. We sought to identify the indications and outcomes for PN in the setting of mRCC with particular attention to different PN subgroups. Materials and Methods We analyzed data from a consecutive cohort of 33 patients with mRCC who underwent PN at a single institution between 1996 and 2011. Non-parametric statistics were used to compare PN subgroups. Overall survival (OS) was estimated using Kaplan-Meier method, and survival functions were compared using the log-rank test. Results Eight patients presented with bilateral synchronous renal masses; 20 with a metachronous contralateral renal mass; and 5 with a unilateral renal mass. Overall, 22 patients (67%) died of disease at a median of 27 months after PN. Patients who underwent PN for a metachronous contralateral renal mass and for a renal mass ≤4cm had the best OS (61 months and 42 months, respectively). Median OS for patients with and without metastatic disease at original diagnosis was 27 and 63 months, respectively (p=0.003). Conclusions Our findings suggest that the presence of metastasis at original diagnosis and the timing of presentation of the PN index lesion play an important role in survival. These factors should be taken into consideration when determining which patients would benefit from partial nephrectomy in the setting of mRCC. PMID:24518767

  13. Clear cell papillary renal cell carcinoma-like tumors in patients with von Hippel-Lindau disease are unrelated to sporadic clear cell papillary renal cell carcinoma.

    PubMed

    Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Martignoni, Guido; Brunelli, Matteo; Wang, Mingsheng; Gobbo, Stefano; Baldridge, Lee Ann; Cheng, Liang

    2013-08-01

    Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease. Gross appearance of CCPRCC-like tumors ranged from yellow-orange to tan, red-brown, or extensively cystic. Histologic features included: small papillary tufts (79%), branched tubules (71%), branched papillae (64%), flattened peripheral cysts (64%), and apically aligned nuclei (43%). Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%). Three tumors (27%) showed strong AMACR staining. Chromosome 3p deletion was often present (82%), similar to that observed in clear cell renal cell carcinomas (80%); no CCPRCC-like tumor had chromosome 7 or 17 abnormalities. In summary, tumors that histologically resemble CCPRCC sometimes occur in patients with VHL disease but usually lack the characteristic immunohistochemical and molecular profile, suggesting that they do not share the same pathogenesis. PMID:23648463

  14. Targeted therapy for renal cell carcinoma: a new treatment paradigm

    PubMed Central

    2007-01-01

    Metastatic clear cell renal cell cancer has traditionally been treated with cytokines (interferon or interleukin-2). Improved understanding of biology has engendered novel targeted therapeutic agents that have altered the natural history of this disease. The vascular endothelial growth factor and its related receptor and the mTOR signal transduction pathway have particularly been exploited. Sunitinib malate, sorafenib tosylate, temsirolimus, and bevacizumab have improved clinical outcomes in randomized trials. Other multitargeted tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic agents (VEGF Trap, lenalidomide) have also demonstrated activity in early studies. Combinations of these agents are being evaluated. The future of the therapy of renal cancer appears promising owing to the efficacy of these novel agents. PMID:17637878

  15. The Epigenetics of Renal Cell Tumors: from Biology to Biomarkers

    PubMed Central

    Henrique, Rui; Luís, Ana Sílvia; Jerónimo, Carmen

    2012-01-01

    Renal cell tumors (RCT) collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological, and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling/histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis, and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided. PMID:22666228

  16. Laparoscopic Partial Nephrectomy for Renal-Cell Carcinoma During Pregnancy

    PubMed Central

    Yuruk, Emrah; Ucpinar, Burak; Binbay, Zerrin; Colakerol, Aykut; Muslumanoglu, Ahmet Yaser

    2016-01-01

    Abstract Background: The incidence of renal-cell carcinoma (RCC) is low during pregnancy. There are different approaches for timing of surgery and treatment modalities for RCC in pregnant women in the literature. To our knowledge, this is the first laparoscopic partial nephrectomy case in a pregnant woman. Case Presentation: Herein, we present a 34-year-old woman with a renal mass at her 14th gestational week. She was admitted to our clinic after a right renal mass was incidentally diagnosed during routine antenatal ultrasonography. MRI revealed a completely endophytic tumor of 6 × 6.5 × 6.5 cm, located in the upper half of the right kidney. We performed laparoscopic partial nephrectomy in our patient and the postoperative course was uneventful. Conclusion: This is the first presented laparoscopic partial nephrectomy case in a pregnant patient. Nephron-sparing surgeries can be performed laparoscopically in appropriate sized renal tumors in suitable pregnant patients.

  17. Tubulocystic renal cell carcinoma: Report of a rare case

    PubMed Central

    Kakkar, Aanchal; Sharma, Mehar C.; Uppal, Manpreet; Chumber, Sunil

    2015-01-01

    Cystic neoplasms of the kidney are rare, and present a unique diagnostic challenge. We report the case of an elderly male who presented with a large cystic neoplasm, which was a diagnostic dilemma clinically and radiologically. Histopathological examination showed a tumour composed of variably sized tubules lined by atypical cells having large round nuclei with prominent nucleoli. Hobnailing was seen at places. Tumour cells were immunopositive for pancytokeratin, vimentin, CD10, CK19 and AMACR, confirming a diagnosis of tubulocystic renal cell carcinoma (TC-RCC). PMID:26425234

  18. Tubulocystic renal cell carcinoma: Report of a rare case.

    PubMed

    Kakkar, Aanchal; Sharma, Mehar C; Uppal, Manpreet; Chumber, Sunil

    2015-01-01

    Cystic neoplasms of the kidney are rare, and present a unique diagnostic challenge. We report the case of an elderly male who presented with a large cystic neoplasm, which was a diagnostic dilemma clinically and radiologically. Histopathological examination showed a tumour composed of variably sized tubules lined by atypical cells having large round nuclei with prominent nucleoli. Hobnailing was seen at places. Tumour cells were immunopositive for pancytokeratin, vimentin, CD10, CK19 and AMACR, confirming a diagnosis of tubulocystic renal cell carcinoma (TC-RCC). PMID:26425234

  19. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.

    PubMed

    Kobayashi, Hanako; Liu, Qingdu; Binns, Thomas C; Urrutia, Andres A; Davidoff, Olena; Kapitsinou, Pinelopi P; Pfaff, Andrew S; Olauson, Hannes; Wernerson, Annika; Fogo, Agnes B; Fong, Guo-Hua; Gross, Kenneth W; Haase, Volker H

    2016-05-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2-/- renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2-/- mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  20. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

    PubMed Central

    Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

    2016-01-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  1. Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma

    PubMed Central

    Guddati, Achuta K.; Marak, Creticus P.

    2012-01-01

    Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients. PMID:22679431

  2. RENAL CELL CARCINOMA METASTASIS TO THE SINONASAL CAVITY: CASE REPORT.

    PubMed

    Kovačić, Marijan; Krvavica, Ana; Rudić, Milan

    2015-06-01

    Renal cell carcinoma accounts for 3% of all adult malignant tumors. Common sites of metastases are lungs, bone, liver, brain and adrenal glands. Metastatic disease to the head and neck ranges from 15% to 30%. The 5-year survival rate after nephrectomy is 60%-75%, but with multiorgan metastases the 5-year survival rate is significantly lower, 0-7%. A case is presented of a female patient diagnosed with renal cell carcinoma metastases to the paranasal sinuses, diagnosed and treated at the Department of ENT and Head and Neck Surgery, Zadar General Hospital, Zadar, Croatia. The tumor was surgically removed. Unfortunately, the patient died one year after the procedure due to multiorgan failure. Although metastases of renal cell carcinoma to the head and neck are very rare, it should be first suspected when investigating a metastatic tumor in this region. Surgical excision offers the best hope for long term survival. In case of unresectable tumor, other treatment options should be considered such as radiotherapy, immunotherapy and chemotherapy. PMID:26415321

  3. Genomic profiling of renal cell carcinoma in patients with end-stage renal disease.

    PubMed

    Inoue, Toru; Matsuura, Keiko; Yoshimoto, Taichiro; Nguyen, Lam Tung; Tsukamoto, Yoshiyuki; Nakada, Chisato; Hijiya, Naoki; Narimatsu, Takahiro; Nomura, Takeo; Sato, Fuminori; Nagashima, Yoji; Kashima, Kenji; Hatakeyama, Shingo; Ohyama, Chikara; Numakura, Kazuyuki; Habuchi, Tomonori; Nakagawa, Masayuki; Seto, Masao; Mimata, Hiromitsu; Moriyama, Masatsugu

    2012-03-01

    The purpose of the present study was to determine the genomic profile of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) by analyzing genomic copy number aberrations. Seventy-nine tumor samples from 63 patients with RCC-ESRD were analyzed by array comparative genomic hybridization using the Agilent Whole Human Genome 4 × 44K Oligo Micro Array (Agilent Technologies Inc., Palo Alto, CA, USA). Unsupervised hierarchical clustering analysis revealed that the 63 cases could be divided into two groups, Clusters A and B. Cluster A was comprised mainly of clear cell RCC (CCRCC), whereas Cluster B was comprised mainly of papillary RCC (PRCC), acquired cystic disease (ACD)-associated RCC, and clear cell papillary RCC. Analysis of the averaged frequencies revealed that the genomic profiles of Clusters A and B resembled those of sporadic CCRCC and sporadic PRCC, respectively. Although it has been proposed on the basis of histopathology that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD are distinct subtypes, the present data reveal that the genomic profiles of these types, categorized as Cluster B, resemble one another. Furthermore, the genomic profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one tissue tended to resemble one another. On the basis of genomic profiling of RCC-ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of sporadic CCRCC. Although various histologic subtypes of non-clear cell RCC-ESRD have been proposed, their genomic profiles resemble those of sporadic PRCC, suggesting that the molecular pathogenesis of non-CCRCC-ESRD may be related to that of sporadic PRCC. PMID:22145865

  4. Overexpression of SATB1 Is Associated with Biologic Behavior in Human Renal Cell Carcinoma

    PubMed Central

    Liu, Lian; Zeng, Fuqing; Xing, Shi'an; Wu, Xiaofei; Chen, Xuepan; Zhu, Zhaohui

    2014-01-01

    Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be aberrantly expressed in various cancers and correlated with the malignant behavior of cancer cells. However, the function of SATB1 in RCC remains unclear. With the combination of immunohistochemistry, western blotting, immunofluorescence, qRT-PCR, and cell proliferation, migration and invasion assays, we found that levels of SATB1 mRNA and protein were dramatically increased in human ccRCC tissues (P<0.001 for both), and upregulation of SATB1 was significantly associated with depth of invasion (P<0.001), lymph node status (P = 0.001) and TNM stage (P = 0.009). SATB1 knockdown inhibited the proliferation, migration and invasion of 786-O cells, whereas SATB1 overexpression promoted the growth and aggressive phenotype of ACHN cells in vitro. Furthermore, SATB1 expression was positively correlated with ZEB2 expression (P = 0.013), and inversely linked to levels of SATB2 and E-cadherin (P = 0.005 and P<0.001, respectively) in ccRCC tissues. Our data provide a basis for the concept that overexpression of SATB1 may play a critical role in the acquisition of an aggressive phenotype for RCC cells through EMT, providing new insights into the significance of SATB1 in invasion and metastasis of ccRCC, which may contribute to fully elucidating the exact mechanism of development and progression of RCC. PMID:24835085

  5. Formulation of selected renal cells for implantation into a kidney.

    PubMed

    Halberstadt, Craig; Robbins, Neil; McCoy, Darell W; Guthrie, Kelly I; Bruce, Andrew T; Knight, Toyin A; Payne, Richard G

    2013-01-01

    Delivery of cells to organs has primarily relied on formulating the cells in a nonviscous liquid carrier. We have developed a methodology to isolate selected renal cells (SRC) that have provided functional stability to damaged kidneys in preclinical models (Kelley et al. Poster presentation at 71st scientific sessions of American diabetes association , 2011; Kelley et al. Oral presentation given at Tissue Engineering and Regenerative Medicine International Society (TERMIS)-North America annual conference, 2010; Presnell et al. Tissue Eng Part C Methods 17:261-273, 2011; Kelley et al. Am J Physiol Renal Physiol 299:F1026-F1039, 2010). In order to facilitate SRC injection into the kidney of patients who have chronic kidney disease, we have developed a strategy to immobilize the cells in a hydrogel matrix. This hydrogel (gelatin) supports cells by maintaining them in a three-dimensional state during storage and shipment (both at cold temperatures) while facilitating the delivery of cells by liquefying when engrafting into the kidney. This chapter will define a method for the formulation of the kidney epithelial cells within a hydrogel. PMID:23494437

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

    SciTech Connect

    Okano, Kazuhiro Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

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

  7. Unclassified Renal Cell Carcinoma With Medullary Phenotype Versus Renal Medullary Carcinoma: Lessons From Diagnosis in an Italian Man Found to Harbor Sickle Cell Trait

    PubMed Central

    Colombo, Piergiuseppe; Smith, Steven C.; Massa, Simona; Renne, Salvatore L.; Brambilla, Simona; Peschechera, Roberto; Graziotti, Pierpaolo; Roncalli, Massimo; Amin, Mahul B.

    2015-01-01

    Medullary carcinoma is a rare malignant tumor of the kidney. It affects individuals of African descent and all cases reported show evidence of sickle cell trait. We reviewed an unusual carcinoma arising in a white man, the ninth in the literature. The tumor demonstrated features associated with renal medullary carcinoma, or unclassified renal cell carcinoma, medullary phenotype as recently described; the presence of sickle cell trait confirmed the diagnosis of medullary carcinoma. This case is helpful in the differential diagnosis with non-sickle cell associated “renal cell carcinoma, unclassified with medullary phenotype,” and study of this spectrum of tumors is ongoing. PMID:26793557

  8. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

    EPA Science Inventory

    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  9. Urinary signatures of Renal Cell Carcinoma investigated by peptidomic approaches.

    PubMed

    Chinello, Clizia; Cazzaniga, Marta; De Sio, Gabriele; Smith, Andrew James; Gianazza, Erica; Grasso, Angelica; Rocco, Francesco; Signorini, Stefano; Grasso, Marco; Bosari, Silvano; Zoppis, Italo; Dakna, Mohammed; van der Burgt, Yuri E M; Mauri, Giancarlo; Magni, Fulvio

    2014-01-01

    Renal Cell Carcinoma (RCC) is typically asymptomatic and surgery usually increases patient's lifespan only for early stage tumours. Moreover, solid renal masses cannot be confidently differentiated from RCC. Therefore, markers to distinguish malignant kidney tumours and for their detection are needed. Two different peptide signatures were obtained by a MALDI-TOF profiling approach based on urine pre-purification by C8 magnetic beads. One cluster of 12 signals could differentiate malignant tumours (n = 137) from benign renal masses and controls (n = 153) with sensitivity of 76% and specificity of 87% in the validation set. A second cluster of 12 signals distinguished clear cell RCC (n = 118) from controls (n = 137) with sensitivity and specificity values of 84% and 91%, respectively. Most of the peptide signals used in the two models were observed at higher abundance in patient urines and could be identified as fragments of proteins involved in tumour pathogenesis and progression. Among them: the Meprin 1α with a pro-angiogenic activity, the Probable G-protein coupled receptor 162, belonging to the GPCRs family and known to be associated with several key functions in cancer, the Osteopontin that strongly correlates to tumour stages and invasiveness, the Phosphorylase b kinase regulatory subunit alpha and the SeCreted and TransMembrane protein 1. PMID:25202906

  10. Urinary Signatures of Renal Cell Carcinoma Investigated by Peptidomic Approaches

    PubMed Central

    De Sio, Gabriele; Smith, Andrew James; Gianazza, Erica; Grasso, Angelica; Rocco, Francesco; Signorini, Stefano; Grasso, Marco; Bosari, Silvano; Zoppis, Italo; Dakna, Mohammed; van der Burgt, Yuri E. M.; Mauri, Giancarlo; Magni, Fulvio

    2014-01-01

    Renal Cell Carcinoma (RCC) is typically asymptomatic and surgery usually increases patient's lifespan only for early stage tumours. Moreover, solid renal masses cannot be confidently differentiated from RCC. Therefore, markers to distinguish malignant kidney tumours and for their detection are needed. Two different peptide signatures were obtained by a MALDI-TOF profiling approach based on urine pre-purification by C8 magnetic beads. One cluster of 12 signals could differentiate malignant tumours (n = 137) from benign renal masses and controls (n = 153) with sensitivity of 76% and specificity of 87% in the validation set. A second cluster of 12 signals distinguished clear cell RCC (n = 118) from controls (n = 137) with sensitivity and specificity values of 84% and 91%, respectively. Most of the peptide signals used in the two models were observed at higher abundance in patient urines and could be identified as fragments of proteins involved in tumour pathogenesis and progression. Among them: the Meprin 1α with a pro-angiogenic activity, the Probable G-protein coupled receptor 162, belonging to the GPCRs family and known to be associated with several key functions in cancer, the Osteopontin that strongly correlates to tumour stages and invasiveness, the Phosphorylase b kinase regulatory subunit alpha and the SeCreted and TransMembrane protein 1. PMID:25202906

  11. DOG1, cyclin D1, CK7, CD117 and vimentin are useful immunohistochemical markers in distinguishing chromophobe renal cell carcinoma from clear cell renal cell carcinoma and renal oncocytoma.

    PubMed

    Zhao, Wei; Tian, Bo; Wu, Chao; Peng, Yan; Wang, Hui; Gu, Wen-Li; Gao, Feng-Hou

    2015-04-01

    The distinction between chromophobe renal cell carcinoma (ChRCC), clear cell renal cell carcinoma (CRCC) and renal oncocytoma may cause a diagnostic dilemma. The usefulness of DOG1, cyclin D1, CK7, CD117 and vimentin in the differential diagnosis of these renal epithelial tumors was investigated. DOG1 was positive in ChRCC (32 of 32, 100%) and in renal oncocytoma (21 of 21, 100%). In contrast, DOG1 was absent in all CRCC (0 of 30). Cyclin D1 was positive in renal oncocytomas (17 of 21, 81%) but negative in the ChRCC (0/23) and CRCC (0 of 30). CK7 was positive in ChRCC (30 of 32, 94%), but was negative in oncocytoma (only scattered single positive cells), and was only focal positive in two cases of CRCC. CD117 was expressed in 88% of ChRCC (28 of 32), 86% of renal oncocytoma (18 of 21), and was negative in all CRCC (0 of 30). Twenty-six of the 30 cases of CRCC were positive (87%) for vimentin with prominent membrane staining patterns. All 23 chromophobe carcinomas were negative for vimentin and 15 of 21 oncocytomas demonstrated focal vimentin positivity, but less than 10%. The above results demonstrate that: (1) DOG1 was very sensitive and specific marker for distinguish ChRCC from CRCC; (2) Cyclin D1 was a useful marker to discriminate between ChRCC and renal oncocytoma; (3) CK7 and CD117 were useful markers to distinguish ChRCC from renal oncocytoma and CRCC. (4) Vimentin was helpful for distinguishing clear cell RCC from chromophobe and oncocytoma (87% of clear cell RCC positive, negative in chromophobe, only focally positive in oncocytoma). (5) CK8/18, CK19, CD10, β-catenin and E-cadherin could not be used to distinguish ChRCC from renal oncocytoma and CRCC. PMID:25596994

  12. The clinical implications of the genetics of renal cell carcinoma.

    PubMed

    Rosner, Inger; Bratslavsky, Gennady; Pinto, Peter A; Linehan, W Marston

    2009-01-01

    Over the last several decades, the advances in molecular genetics have elucidated kidney cancer gene pathways. Kidney cancer is a heterogeneous disorder. Each specific type of kidney cancer has its own histologic features, gene, and clinical course. Insight into the genetic basis of kidney cancer has been learned largely from the study of the familial or hereditary forms of kidney cancer. Extirpative surgery is currently the treatment of choice for kidney cancer that is confined to the kidney. Treatment for advanced or metastatic kidney cancer is a formidable challenge with the traditional therapies currently available. However, investigation of the Mendelian single-gene syndromes, like von Hippel Lindau (VHL: VHL gene), hereditary papillary renal carcinoma (HPRC: c-Met gene), Birt-Hogg-Dubé (BHD: BHD gene), and hereditary leiomyomatosis renal cell cancer (HLRCC: fumarate hydratase gene) provides an opportunity to develop pathway specific therapies. Advances in molecular therapeutics offer novel treatment options for patients with advanced disease. PMID:19285230

  13. Fibroblast activation protein predicts prognosis in clear cell renal cell carcinoma.

    PubMed

    López, José I; Errarte, Peio; Erramuzpe, Asier; Guarch, Rosa; Cortés, Jesús M; Angulo, Javier C; Pulido, Rafael; Irazusta, Jon; Llarena, Roberto; Larrinaga, Gorka

    2016-08-01

    Clear cell renal cell carcinoma is a complex disease with only partial response to therapy and scarce reliable clinical parameters indicative of progression and survival. Fibroblast activation protein expression has been correlated with prognosis in several malignancies but never in renal cancer. We aim to analyze the immunohistochemical expression of fibroblast activation protein in 208 clear cell renal cell carcinomas and to evaluate its impact on the prognosis and survival. A positive cytoplasmic immunostaining of this protein in the stromal fibroblasts associated to cancer cells is associated with large tumor diameter (≥4cm), high-grade (G3/4) tumors, and high-stage (≥pT3) tumors. Fibroblast activation protein-positive cases had significantly shorter survivals after 5 (P=.00015), 10 (P=.0000042), and 15 (P=.000043) years of follow-up, with a hazard ratio of 0.31. Multivariate analysis showed that fibroblast activation protein (P=.00117) was stronger than grade and stage in predicting clinical aggressiveness in clear cell renal cell carcinoma. This study confirms the usefulness of fibroblast activation protein detection in the stromal fibroblast associated to cancer in clear cell renal cell carcinoma and adds a new immunohistochemical marker to predict clinical behavior in these patients. PMID:27063470

  14. The establishment of KORCC (KOrean Renal Cell Carcinoma) database

    PubMed Central

    Hong, Sung Kyu; Lee, Sangchul; Kook, Ha Rim; Lee, Eunsik; Kim, Hyeon Hoe; Kwak, Cheol; Ku, Ja Hyeon; Jeong, Chang Wook; Lee, Ji Youl; Hong, Sung Hoo; Kim, Yong-June; Hwang, Eu Chang; Kwon, Tae Gyun; Kim, Tae-Hwan; Kang, Seok Ho; Kim, Sung Han; Chung, Jinsoo

    2016-01-01

    Purpose The purpose of this article is to report establishment of the 1st Web-based database (DB) system to collect renal cell carcinoma (RCC) data in Korea. Materials and Methods The new Web-based DB system was established to collect basic demographic and clinicopahtological characteristics of a large cohort of patients with RCC in Korea. Data from a total of 6,849 patients were collected from 8 tertiary care hospitals that agreed to participate in organizing the Korean Renal Cell Carcinoma (KORCC) study group as of 1 July 2015. Basic demographic and clinicopathological characteristics were collected. The data of patients who underwent surgical treatments were analyzed to characterize Korean RCC. Results We established the 1st Web-based DB of Korean RCC, a database comprising renal mass management cases from multiple centers in Korea. The data of 5,281 patients who underwent surgical management (mean follow-up, 32 months) were analyzed. The most common symptom was incidentally detected renal mass (76.9%). Clinical T1a was the most common (54.3%) stage and mean tumor size was 4.8±4.2 cm. Radical nephrectomy accounted for 62.7% of cases and an open approach was used in 50.7% and 52.2% of radical and partial nephrectomies, respectively. The 5-year overall, cancer-specific and recurrence-free survival rates were 88.1%, 92.2%, and 88.0%, respectively. Conclusions We report the 1st establishment of a Web-based DB system to collect RCC data in Korea. This DB system will provide a solid basis for the characterization of Korean RCC. PMID:26966726

  15. CT and US Findings of Multilocular Cystic Renal Cell Carcinoma

    PubMed Central

    Kim, Kie Hwan; Lee, Jun Woo

    2000-01-01

    Objective Multilocular cystic renal cell carcinoma (MCRCC) is a recently described variety of renal cell carcinoma with characteristic pathologic and clinical features. The purpose of this study was to analyze the imaging findings of MCRCCs. Materials and Methods Ten adult patients with pathologically proven unilateral MCRCC who underwent renal US and CT were included in this study. The radiologic findings were retrospectively evaluated for cystic content, wall, septum, nodularity, calcification and solid portion by three radiologists who established a consensus. Imaging and postnephrectomy pathologic findings were compared. Results All patients were adults (six males and four females) and their ages ranged from 33 to 68 years (mean, 46). On US and CT images, all tumors appeared as well-defined multilocular cystic masses composed of serous or complicated fluid. In all patients, unenhanced CT scans revealed hypodense cystic portions, and in four tumors, due to the presence of hemorrhage or gelatinous fluid, some hyperdense areas were also noted. In no tumor was an expansile solid nodule seen in the thin septa, and in only one was there dystrophic calcification in a septum. Small areas of solid portion constituting less than 10% of the entire lesion were found in six of the ten tumors, and these areas were slightly enhanced on enhanced CT scans. In all patients, imaging and pathologic findings correlated closely. Conclusion On US and CT images, MCRCC appeared as a well-defined multilocular cystic mass with serous, proteinaceous or hemorrhagic fluid, with no expansile solid nodules in the thin septa, and sometimes with small slightly enhanced solid areas. Where radiologic examinations demonstrate a cystic renal mass of this kind in adult males, MCRCC should be included in the differential diagnosis. PMID:11752938

  16. An obscure cause of gastrointestinal bleeding: Renal cell carcinoma metastasis to the small bowel.

    PubMed

    Gorski, Robyn L; Jalil, Salah Abdel; Razick, Manver; Jalil, Ala' Abdel

    2015-01-01

    Renal cell carcinoma metastasis to the small intestine is a rare condition. It usually results in gastrointestinal bleeding and it could happen many years after the diagnosis with renal cell cancer. Treatment includes surgery as well as targeted agents such as tyrosine kinases. We report here the case of an 82-year-old man with a past medical history of high-grade renal cell carcinoma and right nephrectomy 6 years earlier, who presented with recurrent episodes of syncope and black stools. He underwent esophagogastroduodenoscopy (EGD) and colonoscopy without evident source of bleeding. Video capsule endoscopy (VCE) showed three bleeding lesions in the jejunum and ileum. Push enteroscopy revealed a proximal jejunum bleeding mass that was suspicious for malignancy. Histopathology demonstrated poorly differentiated carcinoma. Given the patient's history of high-grade renal cell carcinoma, and similarity of histologic changes to the old renal cell cancer specimen, metastatic renal cell carcinoma was felt to be the responsible etiology. PMID:26348395

  17. Establishment of an ASPL-TFE3 renal cell carcinoma cell line (S-TFE).

    PubMed

    Hirobe, Megumi; Masumori, Naoya; Tanaka, Toshiaki; Kitamura, Hiroshi; Tsukamoto, Taiji

    2013-06-01

    Xp11 translocation renal cell carcinoma is a rare disease diagnosed in children and adolescents in the advanced stage with an aggressive clinical course. Various gene fusions including the transcription factor E3 (TFE3) gene located on chromosome X cause the tumor. We established an Xp11 translocation renal cell carcinoma cell line from a renal tumor in a 18-y-old Japanese female and named it "S-TFE." The cell line and its xenograft demonstrated definite gene fusion including TFE3. They showed strong nuclear staining for TFE3 in immunohistochemistry, TFE3 gene rearrangement in dual-color, break-apart FISH analysis and ASPL-TFE3 type 1 fusion transcripts detected by RT-PCR and direct DNA sequencing. Although many renal cell carcinoma cell lines have been established and investigated, only a few cell lines are recognized as Xp11.2 translocation carcinoma. S-TFE will be useful to examine the characteristics and drug susceptibility of Xp11 translocation renal cell carcinoma. PMID:23760492

  18. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-07-06

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  19. Cystic Renal Oncocytoma and Tubulocystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Comparative Study.

    PubMed

    Skenderi, Faruk; Ulamec, Monika; Vranic, Semir; Bilalovic, Nurija; Peckova, Kvetoslava; Rotterova, Pavla; Kokoskova, Bohuslava; Trpkov, Kiril; Vesela, Pavla; Hora, Milan; Kalusova, Kristyna; Sperga, Maris; Perez Montiel, Delia; Alvarado Cabrero, Isabel; Bulimbasic, Stela; Branzovsky, Jindrich; Michal, Michal; Hes, Ondrej

    2016-02-01

    Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity. Immunohistochemical panel included various cytokeratins (AE1-AE3, OSCAR, CAM5.2, CK7), vimentin, CD10, CD117, AMACR, CA-IX, antimitochondrial antigen (MIA), EMA, and Ki-67. The presence of at least focal solid growth and islands of tumor cells interspersed with loose stroma, lower ISUP nucleolar grade, absence of necrosis, and absence of mitotic figures were strongly suggestive of a cystic RO. In contrast, the absence of solid and island growth patterns and presence of more compact, fibrous stroma, accompanied by higher ISUP nucleolar grade, focal necrosis, and mitotic figures were all associated with TCRCC. TCRCC marked more frequently for vimentin, CD10, AMACR, and CK7 and had a higher proliferative index by Ki-67 (>15%). CD117 was negative in 14/15 cases. One case was weakly CD117 reactive with cytoplasmic positivity. All cystic RO cases were strongly positive for CD117. The remaining markers (AE1-AE3, CAM5.2, OSCAR, CA-IX, MIA, EMA) were of limited utility. Presence of tumor cell islands and solid growth areas and the type of stroma may be major morphologic criteria in differentiating cystic RO from TCRCC. In difficult cases, or when a limited tissue precludes full morphologic assessment, immunohistochemical pattern of vimentin, CD10, CD117, AMACR, CK7, and Ki-67 could help in establishing the correct diagnosis. PMID:26180933

  20. Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells.

    PubMed Central

    Silkensen, J R; Skubitz, K M; Skubitz, A P; Chmielewski, D H; Manivel, J C; Dvergsten, J A; Rosenberg, M E

    1995-01-01

    The function of clusterin, a heterodimeric glycoprotein markedly induced in renal and other organ injuries, is unclear. Since renal injury is accompanied by alterations in cell attachment, it is possible that clusterin functions to promote cell-cell and cell-substratum interactions. In this study, a single cell suspension of renal epithelial (LLC-PK1) cells was treated with purified human clusterin, resulting in time- and dose-dependent cell aggregation. Electron microscopy of the cell aggregates demonstrated cell junction and lumen formation. To determine the effect of clusterin on cell adhesion, tissue culture plates were coated with clusterin, fibronectin, PBS, or albumin. Clusterin and fibronectin promoted cell adhesion to the same extent. The adhesion to clusterin was dose dependent and specific, as a monoclonal antibody against clusterin inhibited cell adhesion to clusterin but not fibronectin. Perterbations of the cytoskeleton may underlie the alterations in cell attachment which occur in renal injury. Induction of clusterin mRNA was seen after disruption of both microtubules and microfilaments and after inhibition of cell-substratum interactions. In conclusion, clusterin is a potent renal epithelial cell aggregation and adhesion molecule. We speculate that clusterin functions to promote cell-cell and cell-substratum interactions which are perturbed in the setting of renal injury, thereby preserving the integrity of the renal epithelial barrier. Images PMID:8675630

  1. Occupational exposure to dusts and risk of renal cell carcinoma

    PubMed Central

    Karami, S; Boffetta, P; Stewart, P S; Brennan, P; Zaridze, D; Matveev, V; Janout, V; Kollarova, H; Bencko, V; Navratilova, M; Szeszenia-Dabrowska, N; Mates, D; Gromiec, J; Slamova, A; Chow, W-H; Rothman, N; Moore, L E

    2011-01-01

    Background: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case–control study. Methods: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. Results: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1–3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2–5.1), and brick dust (OR: 1.5; 95% CI: 1.0–2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. Conclusion: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings. PMID:21540858

  2. Current Status of Minimally Invasive Surgery for Renal Cell Carcinoma.

    PubMed

    Smith, Zachary L

    2016-06-01

    Over the last three decades, the incidence of renal cell carcinoma (RCC) has continuously risen, generally attributed to the increased use of cross-sectional imaging across all medical disciplines. Fortunately, despite this rising incidence, the estimated 5-year relative survival rate has improved. This survival improvement likely parallels the stage migration of the last two decades toward an increased incidence of small renal masses (SRMs). However, this survival improvement may be secondary to improved surgical techniques and medical therapies for these malignancies. The increased incidence of SRMs has led to an expected evolution in the treatment of RCC. Minimally invasive surgical applications for the treatment of RCC have gained widespread popularity, and now these approaches to renal malignancies have surpassed open techniques in frequency of utilization. Laparoscopic and robotic-assisted techniques have now been applied to both radical and partial nephrectomy procedures of varying complexity. Additionally, percutaneous ablative procedures have been applied to the treatment of some SRMs, increasing the urologist's armamentarium further. Below, we provide a review of these minimally invasive surgical (MIS) procedures for the treatment of RCC. PMID:27021911

  3. Atypical presentations and rare metastatic sites of renal cell carcinoma: a review of case reports

    PubMed Central

    2011-01-01

    Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and a propensity for metastatic spread. Due to the fact that the patterns of metastases from renal cell carcinomas are not clearly defined, there have been several reports of cases of renal cell carcinoma associated with rare metastatic sites and atypical presenting symptoms. The present review focuses on these atypical rare clinical presentations of renal cell carcinomas both at the time of diagnosis of the primary tumor but also in the years after radical nephrectomy. PMID:21888643

  4. Gene expression and cell turnover in human renal dysplasia.

    PubMed

    Woolf, A S; Winyard, P J

    2000-01-01

    Kidney malformations are common causes of chronic renal failure in children. Dysplastic kidneys represent a unique model of perturbed epithelial-mesenchymal interaction which leads to the formation of malformed branching tubules surrounded by undifferentiated and metaplastic mesenchymal cells. We have found that human dysplastic epithelia express PAX2 (a transcription factor), BCL2 (a survival factor) and galectin-3 (a cell adhesion/signaling molecule). These genes are implicated in oncogenesis and their persistent expression may drive proliferation of dysplastic cysts, hence explaining the massive growth of some multicystic dysplastic kidneys. We have also detected prominent apoptosis in undifferentiated tissues around dysplastic epithelia, and this may provide a potential mechanism for the well-documented regression of dysplastic kidneys. Hence, although these kidneys may not have any excretory function, it is incorrect to consider them as 'end stage organs' because they are highly active in terms of cell turnover and gene expression; furthermore, these processes can be correlated with patterns of tissue growth and involution. Further elucidation of 'molecular lesions' in renal malformations may lead to novel therapies to enhance the differentiation of progenitor cells. PMID:10668206

  5. Clear cell papillary renal cell carcinoma and clear cell renal cell carcinoma arising in acquired cystic disease of the kidney: an immunohistochemical and genetic study.

    PubMed

    Kuroda, Naoto; Shiotsu, Tomoyuki; Kawada, Chiaki; Shuin, Taro; Hes, Ondrej; Michal, Michal; Ohe, Chisato; Mikami, Shuji; Pan, Chin-Chen

    2011-08-01

    Clear cell papillary renal cell carcinoma (RCC) is a recently established disease entity. However, there are few reports on genetic study of this entity. We report such a case with focus on genetic study. A 57-year-old Japanese man was found to have 3 renal tumors. Histologically, two tumors showed findings of clear cell RCC; and the other tumor showed findings of clear cell papillary RCC that was characterized by papillary growth pattern of neoplastic cells in cystic space with purely clear cell cytology. Immunohistochemically, tumor cells of clear cell papillary RCC were diffusely positive for PAX2 and cytokeratin 7, but negative for CD10, RCC Ma, and AMACR. In fluorescence in situ hybridization study for one clear cell papillary RCC, we detected polysomy for chromosome 7 and monosomy for chromosomes 17, 16, and 20. In addition, we detected mutation of VHL gene in clear cell RCC, but found no VHL gene mutation in clear cell papillary RCC. Finally, our results provide further evidence that clear cell papillary RCC may be both morphologically and genetically distinct entity from clear cell RCC and papillary RCC. PMID:20952286

  6. Transperitoneal laparoscopic right radical nephrectomy for renal cell carcinoma and end-stage renal disease: a case report

    PubMed Central

    2009-01-01

    Nephron-sparing surgery (partial nephrectomy) results are similar to those of radical nephrectomy for small (<4 cm) renal tumors. However, in patients with end-stage renal disease, radical nephrectomy emerges as a more efficient treatment for localized renal cell cancer. Laparoscopic radical nephrectomy (LRN) increasingly is being performed. The objective of the present study was to present a case of a patient under hemodialysis who was submitted to LRN for a small renal mass and discuss the current issues concerning this approach. It appears that radical nephrectomy should be the standard treatment in dialysis patients even for small tumors. The laparoscopic technique is associated with acceptable cancer-specific survival and recurrence rate along with shorter hospital stay, less postoperative pain and earlier return to normal activities. PMID:20062705

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

    PubMed

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

    2015-04-01

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

  8. A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma.

    PubMed

    Kurisaki-Arakawa, Aiko; Saito, Tsuyoshi; Takahashi, Michiko; Mitani, Keiko; Fukumura, Yuki; Nagashima, Yoji; Argani, Pedrum; Yao, Takashi

    2013-01-01

    Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results. PMID:24228124

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

    PubMed

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

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. PMID:26136112

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

    PubMed Central

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

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. PMID:26136112

  11. 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.

    PubMed

    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

  12. Retrograde venous invasion in renal cell carcinoma: a complication of sinus vein and main renal vein invasion.

    PubMed

    Bonsib, Stephen M; Bhalodia, Ami

    2011-12-01

    Renal cell carcinoma, especially clear cell, gains access to the venous system as the initial route of extrarenal spread. Intravenous growth can involve extrarenal veins or renal veins in other portions of the kidney, referred to herein as retrograde venous invasion. This study investigates the incidence and defines the pathological features of retrograde venous invasion. Retrograde venous invasion is defined as rounded nodules of tumor separated from the primary tumor and in a location that conforms to the venous outflow. Nine cases of retrograde venous invasion were identified in a series of 115 renal cell carcinomas (8%). Two blocks from each case were stained with elastic van Gieson, Masson trichrome, CD31 and desmin to evaluate intravenous involvement. All cases were staged using the 2010 TNM staging schema. The tumors ranged in size from 4.2 to 17 cm. All cases showed sinus vein and main renal vein invasion (pT3a); three cases involved the vena cava (pT3b). Direct continuity between the primary tumor and tumor in the main renal vein was grossly evident in every case. Involved sinus veins could be followed retrograde to the cortex between renal pyramids with tumor nodules arrayed along the pyramid-cortex interface. Histologically, the involved parenchymal veins lacked a smooth muscle media and elastica. CD31 demonstrated an endothelial cell lining around many nodules. As intravenous nodules enlarged endothelium was lost, extra-venous invasion occurred and nodules coalesced and merged with the primary tumor. In conclusion, retrograde venous invasion occurred only with main renal vein involvement. Gross evaluation allowed detection in every case. Histological confirmation of intravenous nature is challenging due to the absence of smooth muscle in parenchymal veins. As retrograde growth becomes extensive nodules coalesce and merge with the primary tumor and may be included in measurement of primary tumor size if this process is unrecognized. PMID:21822202

  13. Penoscrotal lymphedema associated with metastatic renal cell carcinoma.

    PubMed

    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

  14. How tubular epithelial cells dictate the rate of renal fibrogenesis?

    PubMed Central

    Louis, Kevin; Hertig, Alexandre

    2015-01-01

    The main threat to a kidney injury, whatever its cause and regardless of whether it is acute or chronic, is the initiation of a process of renal fibrogenesis, since fibrosis can auto-perpetuate and is of high prognostic significance in individual patients. In the clinic, a decrease in glomerular filtration rate correlates better with tubulointerstitial damage than with glomerular injury. Accumulation of the extracellular matrix should not be isolated from other significant cellular changes occurring in the kidney, such as infiltration by inflammatory cells, proliferation of myofibroblasts, obliteration of peritubular capillaries and atrophy of tubules. The aim of this review is to focus on tubular epithelial cells (TEC), which, necessarily involved in the repair process, eventually contribute to accelerating fibrogenesis. In the context of injury, TEC rapidly exhibit phenotypic and functional changes that recall their mesenchymal origin, and produce several growth factors known to activate myofibroblasts. Because they are high-demanding energy cells, TEC will subsequently suffer from the local hypoxia that progressively arises in a microenvironment where the matrix increases and capillaries become rarified. The combination of hypoxia and metabolic acidosis may induce a vicious cycle of sustained inflammation, at the center of which TEC dictate the rate of renal fibrogenesis. PMID:26167460

  15. Mast cell stabilizers obviate high fat diet-induced renal dysfunction in rats.

    PubMed

    Reena; Kaur, Tajpreet; Kaur, Anudeep; Singh, Manjinder; Buttar, Harpal Singh; Pathak, Devendra; Singh, Amrit Pal

    2016-04-15

    The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats. PMID:26944217

  16. The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis.

    PubMed

    Myszczyszyn, Adam; Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Lian, Fei; Kornakiewicz, Anna; Bartnik, Ewa; Kukwa, Wojciech; Kieda, Claudine; Szczylik, Cezary

    2015-12-01

    The cancer stem cell (CSC) model has recently been approached also in renal cell carcinoma (RCC). A few populations of putative renal tumor-initiating cells (TICs) were identified, but they are indifferently understood; however, the first and most thoroughly investigated are CD105-positive CSCs. The article presents a detailed comparison of all renal CSC-like populations identified by now as well as their presumable origin. Hypoxic activation of hypoxia-inducible factors (HIFs) contributes to tumor aggressiveness by multiple molecular pathways, including the governance of immature stem cell-like phenotype and related epithelial-to-mesenchymal transition (EMT)/de-differentiation, and, as a result, poor prognosis. Due to intrinsic von Hippel-Lindau protein (pVHL) loss of function, clear-cell RCC (ccRCC) develops unique pathological intra-cellular pseudo-hypoxic phenotype with a constant HIF activation, regardless of oxygen level. Despite satisfactory evidence concerning pseudo-hypoxia importance in RCC biology, its influence on putative renal CSC-like largely remains unknown. Thus, the article discusses a current knowledge of HIF-1α/2α signaling pathways in the promotion of undifferentiated tumor phenotype in general, including some experimental findings specific for pseudo-hypoxic ccRCC, mostly dependent from HIF-2α oncogenic functions. Existing gaps in understanding both putative renal CSCs and their potential connection with hypoxia need to be filled in order to propose breakthrough strategies for RCC treatment. PMID:26210994

  17. Cell Adhesion Molecules in Chemically-Induced Renal Injury

    PubMed Central

    Prozialeck, Walter C.; Edwards, Joshua R.

    2007-01-01

    Cell adhesion molecules are integral cell-membrane proteins that maintain cell-cell and cell-substrate adhesion, and in some cases, act as regulators of intracellular signaling cascades. In the kidney, cell adhesion molecules such as the cadherins, the catenins, ZO-1, occludin and the claudins are essential for maintaining the epithelial polarity and barrier integrity that are necessary for the normal absorption/excretion of fluid and solutes. A growing volume of evidence indicates that these cell adhesion molecules are important early targets for a variety of nephrotoxic substances including metals, drugs, and venom components. In addition, it is now widely appreciated that molecules such as ICAM-1, the integrins and selectins play important roles in the recruitment of leukocytes and inflammatory responses that are associated with nephrotoxic injury. This review summarizes the results of recent in vitro and in vivo studies indicating that these cell adhesion molecules may be primary molecular targets in many types of chemically-induced renal injury. Some of the specific agents that are discussed include Cd, Hg, Bi, cisplatin, aminoglycoside antibiotics, S-(1,2-dichlorovinyl-L-cysteine) (DCVC) and various venom toxins. This review also includes a discussion of the various mechanisms by which these substances can affect cell adhesion molecules in the kidney. PMID:17316817

  18. Renal cell carcinoma: presentation, staging, and surgical treatment.

    PubMed

    Russo, P

    2000-04-01

    The widespread availability of abdominal ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scanning has increased the diagnosis of incidental renal tumors, which now comprise the vast majority of the new cases diagnosed each year. With the detection of renal tumors at an earlier stage, partial nephrectomy and nephron-sparing surgery have evolved as effective alternatives to radical nephrectomy. The poor prognostic findings of involved regional lymph nodes or ipsilateral adrenal metastases has led to more selective operations on those sites in the face of incidental tumor detection. Technological advances have allowed for the development by committed surgical investigators of techniques of laparoscopic and laparoscopically assisted nephrectomy. Although not widely employed, further improvements in technology may widen the appeal of these approaches to selected renal tumors. Advances in cardiovascular surgical techniques have made resection of renal cell carcinoma (RCC) with tumor thrombi involving the inferior vena cava (IVC) possible, although this approach is still associated with significant perioperative mortality depending on the degree of caval involvement. In highly selected cases, resection of limited metastatic disease is recommended, particularly if the disease-free interval is greater than 12 months and there is a only a single site of metastatic disease. Whether metastectomy is therapeutic or fits within the realm of the often long and unpredictable natural history of RCC is not known. Strategies for follow-up are based primarily on the pathologic stage of the operated tumor. Small incidental tumors have an excellent prognosis and require little in the way of postoperative imaging. As the pathologic stage increases, the likelihood of developing metastatic disease increases, necessitating biannual chest x-ray in addition to history and physical examination. Symptom-directed bone scans and CT scans are effective in identifying most

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

    PubMed Central

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

    2012-01-01

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

  20. Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized 13C pyruvate magnetic resonance

    PubMed Central

    Sriram, Renuka; Van Criekinge, Mark; DeLos Santos, Justin; Keshari, Kayvan R.; Wilson, David M.; Peehl, Donna; Kurhanewicz, John; Wang, Zhen J.

    2016-01-01

    Localized renal tumors are increasingly detected incidentally at imaging. Conventional imaging cannot reliably differentiate the 20% of these tumors that are benign from malignant renal cell carcinomas (RCCs), leading to unnecessary surgical resection and resulting morbidity associated with surgery. Here, we investigated hyperpolarized 13C pyruvate metabolism in live patient-derived renal tumor tissue slices using a novel magnetic resonance (MR) -compatible bioreactor platform. We demonstrated for the first time that clear cell RCCs (ccRCCs), which account for 70–80% of all RCCs, have increased lactate production as well as rapid lactate efflux compared to benign renal tumors. This difference is attributed to increased lactate dehydrogenase A and monocarboxylate transporter 4 expression in ccRCCs. This distinctive metabolic phenotype can be used to differentiate RCCs from benign renal tumors using clinically translatable hyperpolarized 13C pyruvate MR. PMID:27227168

  1. Kidney injury molecule-1 (KIM-1) mediates renal epithelial cell repair via ERK MAPK signaling pathway

    PubMed Central

    Zhang, Zhiwei; Cai, Cindy X

    2016-01-01

    The expression of kidney injury molecule-1 (KIM-1), a very promising sensitive and specific urinary biomarker for acute renal injury, is markedly upregulated in injured and regenerating renal proximal tubular epithelial cells following ischemic or toxic insults, suggesting a possible role for this molecule in renal repair process. In the present study we report that expression of KIM-1 facilitates renal tubular epithelial cell repair by promoting cell migration and proliferation. KIM-1 expression also enhances ERK MAPK activation, and the modulatory effect of KIM-1 on cellular repair process is likely mediated via ERK MAPK signaling pathway. PMID:27084535

  2. Kidney injury molecule-1 (KIM-1) mediates renal epithelial cell repair via ERK MAPK signaling pathway.

    PubMed

    Zhang, Zhiwei; Cai, Cindy X

    2016-05-01

    The expression of kidney injury molecule-1 (KIM-1), a very promising sensitive and specific urinary biomarker for acute renal injury, is markedly upregulated in injured and regenerating renal proximal tubular epithelial cells following ischemic or toxic insults, suggesting a possible role for this molecule in renal repair process. In the present study, we report that expression of KIM-1 facilitates renal tubular epithelial cell repair by promoting cell migration and proliferation. KIM-1 expression also enhances ERK MAPK activation, and the modulatory effect of KIM-1 on cellular repair process is likely mediated via ERK MAPK signaling pathway. PMID:27084535

  3. Immune signature of tumor infiltrating immune cells in renal cancer

    PubMed Central

    Geissler, Katharina; Fornara, Paolo; Lautenschläger, Christine; Holzhausen, Hans-Jürgen; Seliger, Barbara; Riemann, Dagmar

    2015-01-01

    Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 = 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients’ survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DR+ and CXCR3+ T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients. PMID:25949868

  4. Clear cell renal cell carcinoma with vaginal and brain metastases: a case report and literature review

    PubMed Central

    Momah, Tobe; Dhanan, Etwaru; Xiao, Phillip; Kondamudi, Vasantha

    2009-01-01

    There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.

  5. Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas.

    PubMed Central

    Kovacs, G; Kung, H F

    1991-01-01

    For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. We have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease; we then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. We developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (i) in one step or (ii) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors. Images PMID:1986366

  6. Canadian guideline on genetic screening for hereditary renal cell cancers

    PubMed Central

    Reaume, M. Neil; Graham, Gail E.; Tomiak, Eva; Kamel-Reid, Suzanne; Jewett, Michael A.S.; Bjarnason, Georg A.; Blais, Normand; Care, Melanie; Drachenberg, Darryl; Gedye, Craig; Grant, Ronald; Heng, Daniel Y.C.; Kapoor, Anil; Kollmannsberger, Christian; Lattouf, Jean-Baptiste; Maher, Eamonn R.; Pause, Arnim; Ruether, Dean; Soulieres, Denis; Tanguay, Simon; Turcotte, Sandra; Violette, Philippe D.; Wood, Lori; Basiuk, Joan; Pautler, Stephen E.

    2013-01-01

    Background: Hereditary renal cell cancer (RCC) is an ideal model for germline genetic testing. We propose a guideline of hereditary RCC specific criteria to suggest referral for genetic assessment. Methods: A review of the literature and stakeholder resources for existing guidelines or consensus statements was performed. Referral criteria were developed by expert consensus. Results: The criteria included characteristics for patients with RCC (age ≤45 years, bilateral or multifocal tumours, associated medical conditions and non-clear cell histologies with unusual features) and for patients with or without RCC, but a family history of specific clinical or genetic diagnoses. Conclusions: This guideline represents a practical RCC-specific reference to allow healthcare providers to identify patients who may have a hereditary RCC syndrome, without extensive knowledge of each syndrome. RCC survivors and their families can also use the document to guide their discussions with healthcare providers about their need for referral. The criteria refer to the most common hereditary renal tumour syndromes and do not represent a comprehensive or exclusive list. Prospective validation of the criteria is warranted. PMID:24319509

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

    PubMed

    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. PMID:27453294

  8. Expression of osteopontin and CD44 molecule in papillary renal cell tumors.

    PubMed

    Matusan, Koviljka; Dordevic, Gordana; Mozetic, Vladimir; Lucin, Ksenija

    2005-01-01

    The aim of the study was to analyze the expression of CD44 adhesion molecule and its ligand osteopontin in papillary renal cell tumors, and to assess the possible prognostic significance of CD44 and osteopontin expression in papillary renal cell carcinomas. The expression of the standard and v6 exon containing isoforms of CD44 molecule, as well as of its ligand osteopontin, was immunohistochemically evaluated in 43 papillary renal cell tumors, which included 5 adenomas and 38 carcinomas. In order to assess their prognostic significance, the results obtained in papillary renal cell carcinomas were compared to usual clinicopathological parameters such as tumor size, histological grade, pathological stage, and Ki-67 proliferation index. Normal renal tissue was negative for CD44s and v6 isoforms, while the expression of osteopontin was found in distal tubular epithelial cells in the form of cytoplasmic granular positivity. CD44s and v6 isoforms were upregulated in 22 (58%) and 12 (32%) out of 38 carcinomas, respectively. Among all clinicopathological parameters examined, we only found significant association of CD44s-positive carcinomas with lower pathological stage (p=0.026). Papillary renal cell adenomas were generally negative for CD44s, except for focal positivity found in one sample. The osteopontin protein was detected in all adenomas and all papillary renal cell carcinomas, except one. Our results show constitutive expression of osteopontin in papillary renal tumors, including papillary renal cell adenomas. The upregulation of CD44s and v6 isoforms, although found in a considerable number of papillary renal cell carcinomas, does not appear to have any prognostic value in this type of renal cancer. PMID:15999156

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

    PubMed

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

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response. PMID:27317647

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

    PubMed

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

    2016-08-01

    Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney. PMID:27294565

  11. Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

    PubMed

    Gill, Simpal; Kauffman, Eric C; Kandel, Sirisa; George, Saby; Schwaab, Thomas; Xu, Bo

    2016-05-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection. PMID:26510859

  12. Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

    PubMed

    Teplan, Vladimír; Mahrová, Andrea; Králová-Lesná, Ivana; Racek, Jaroslav; Valkovský, Ivo; Štollová, Milena

    2015-03-01

    Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 μmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 μmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx. PMID:25576240

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

    PubMed Central

    Mohamed, Kamal E.H.

    2016-01-01

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis. PMID:27478584

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

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    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. PMID:19266088

  15. Renal Cancer Stem Cells: Characterization and Targeted Therapies

    PubMed Central

    Sisti, Alessandro; Romagnani, Paola

    2016-01-01

    Renal cell carcinoma (RCC) is a major neoplasm with high incidence in western countries. Tumors are heterogeneous and are composed of differentiated cancer cells, stromal cells, and cancer stem cells (CSCs). CSCs possess two main properties: self-renewal and proliferation. Additionally, they can generate new tumors once transplanted into immunodeficient mice. Several approaches have been described to identify them, through the expression of cell markers, functional assays, or a combination of both. As CSCs are involved in the resistance mechanisms to radio- and chemotherapies, several new strategies have been proposed to directly target CSCs in RCC. One approach drives CSCs to differentiate into cancer cells sensitive to conventional treatments, while the other proposes to eradicate them selectively. A series of innovative therapies aiming at eliminating CSCs have been designed to treat other types of cancer and have not been experimented with on RCC yet, but they reveal themselves to be promising. In conclusion, CSCs are an important player in carcinogenesis and represent a valid target for therapy in RCC patients. PMID:27293448

  16. Clear cell papillary renal cell carcinoma: a clinicopathologic analysis of 6 cases.

    PubMed

    Yan, Wen-Xiu; Cao, Wen-Rong; Zhao, Jun; Zhang, Wei; Wang, Xue-Li; Yuan, Qian; Dang, Shou-Qin

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a newly described variant of renal cell carcinoma (RCC) which is composed mainly of cells with clear cytoplasm arranged in cystic and papillary patterns. We report the clinicopathologic features, prognosis and differential diagnosis of 6 Clear Cell Papillary Renal Cell Carcinomas. The clinical information and follow-up data were analyzed. The patients were six males with median age of 52.5 years. Case 1 revealed dense calcification and ossification. Cases 2 and 3 contain a variably prominent smooth muscle stromal component. CA-IX, CK7, PAX-8 and VIM were positive in all cases. TFE3 and AMACR were not expressed in any tumor. CD10 was negative in 5 of 6 cases .The patients were followed for 13~55 months with no local tumor recurrences and tumor metastasis. The CCPRCC was associated with a more favorable outcome. These were low-grade and low-stage renal tumors. No lymph node or distant metastasis of the six tumors. PMID:26191150

  17. AB241. Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P

    PubMed Central

    Huang, Bin; Wang, Dao-Hu; Chen, Jun-Xing; Qiu, Shao-Peng

    2016-01-01

    Background Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Methods We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Results Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells among five cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Conclusions Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

  18. Meat-cooking mutagens and risk of renal cell carcinoma

    PubMed Central

    Daniel, C R; Schwartz, K L; Colt, J S; Dong, L M; Ruterbusch, J J; Purdue, M P; Cross, A J; Rothman, N; Davis, F G; Wacholder, S; Graubard, B I; Chow, W H; Sinha, R

    2011-01-01

    Background: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case–control study conducted in metropolitan Detroit and Chicago. Methods: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. Results: The risk of RCC increased with intake of barbecued meat (Ptrend=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), Ptrend=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (Pinteraction<0.05). We found no association for HCAs or overall meat intake. Conclusion: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC. PMID:21897389

  19. Metabolic profiling reveals key metabolic features of renal cell carcinoma

    PubMed Central

    Catchpole, Gareth; Platzer, Alexander; Weikert, Cornelia; Kempkensteffen, Carsten; Johannsen, Manfred; Krause, Hans; Jung, Klaus; Miller, Kurt; Willmitzer, Lothar; Selbig, Joachim; Weikert, Steffen

    2011-01-01

    Abstract Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC. PMID:19845817

  20. Electrolyte composition of renal tubular cells in gentamicin nephrotoxicity

    SciTech Connect

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

    1988-06-01

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

  1. microRNA-451 inhibited cell proliferation, migration and invasion through regulation of MIF in renal cell carcinoma

    PubMed Central

    Tang, Yan; Wan, Wei; Wang, Lijuan; Ji, Shishun; Zhang, Juanjuan

    2015-01-01

    The expression and functions of microRNA-451 have been studied in many human cancers. However, up to date, there is no study of microRNA-451 in renal cell carcinoma. In the present study, we aimed to investigate the expression, biological functions and molecular mechanisms of microRNA-451 in renal cell carcinoma. microRNA-451 expression level in renal cell carcinoma tissues and cell lines was measured using quantitative Real-time PCR. By using CCK8 assay, cell migration and invasion assay, we explored the functions of microRNA-451 in renal cell carcinoma. Dual-Luciferase report assay, quantitative Real-time PCR and western blot were performed to explore the molecular mechanisms of microRNA-451 functions in renal cell carcinoma. Functional assays were also performed to explore the effects of endogenous MIF in renal cell carcinoma. In this study, we showed for the first time that microRNA-451 was significantly down-regulated in renal cell carcinomas tissues and cell lines. microRNA-451 expression level was correlated with histological grade and lymph node metastasis. In addition, microRNA-451 inhibited proliferation, migration and invasion of renal cell carcinomas cells. Moreover, MIF was identified as a target of microRNA-451, and down-regulation of MIF could mimic the suppressive functions of microRNA-451 in renal cell carcinomas, suggesting that microRNA-451 might be a novel therapeutic strategy for the treatment of renal cell carcinomas. PMID:26884830

  2. VCL-ALK Renal Cell Carcinoma in Children With Sickle-cell Trait

    PubMed Central

    Smith, Nathaniel E.; Deyrup, Andrea T.; Marinño-Enriquez, Adrian; Fletcher, Jonathan A.; Bridge, Julia A.; Illei, Peter B.; Netto, George J.; Argani, Pedram

    2015-01-01

    We report the third case of a renal cell carcinoma bearing a fusion of the vinculin (VCL) and anaplastic lymphoma kinase (ALK) genes. Like the 2 other reported cases, this neoplasm occurred in a young patient (6 y old) with sickle-cell trait and demonstrated distinctive morphologic features including medullary epicenter, discohesive polygonal or spindle-shaped cells with prominent cytoplasmic vacuoles, and prominent lymphocytic infiltrate. The neoplastic cells demonstrated focal membranous labeling for ALK protein by immunohistochemistry, ALK gene rearrangement by fluorescence in situ hybridization, and a specific VCL-ALK gene fusion by reverse transcriptase polymerase chain reaction. VCL-ALK renal cell carcinoma may represent the eighth sickle-cell nephropathy. PMID:24698962

  3. A Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells

    PubMed Central

    Ocaña-Salceda, Carlos; Sancho, Mónica; Orzáez, Mar; Messeguer, Angel; Ruiz-Ortega, Marta; Egido, Jesús; Vicent, María J.; Ortiz, Alberto; Ramos, Adrián M.

    2013-01-01

    The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-κB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-κB transcriptional activity and chemokine expression, despite failing to inhibit NF-κB-p65 nuclear translocation and NF-κB DNA binding. QM56 prevented JAK2 activation and NF-κB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-1−/− cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by down-modulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance. PMID:23300960

  4. Chrysophanic Acid Induces Necrosis but not Necroptosis in Human Renal Cell Carcinoma Caki-2 Cells

    PubMed Central

    Choi, Joon-Seok

    2016-01-01

    Background: Chrysophanic acid, also known as chrysophanol, has a number of biological activities. It enhances memory and learning abilities, raises superoxide dismutase activity, and has anti-cancer effects in several model systems. According to previous reports, chrysophanic acid-induced cell death shares features of necrotic cell death. However, the molecular and cellular processes underlying chrysophanic acid-induced cell death remain poorly understood. Methods: Chrysophanic acid-induced cell death was monitored by cell viability assay and Annexin V-propidium iodide (PI) staining of renal cell carcinoma Caki-2 cells. The induction of intracellular reactive oxygen species (ROS) by chrysophanic acid and the suppression of ROS by anti-oxidants were evaluated by 2′,7′-dichlorofluorescin diacetate staining. The expression and phosphorylation of proteins that are involved in apoptosis and necroptosis were detected by immunoblotting. Results: The extent of chrysophanic acid-induced cell death was concentration and time dependent, and dead cells mainly appeared in the PI-positive population, which is a major feature of necrosis, upon fluorescence-activated cell sorting analysis. Chrysophanic acid-induced cell death was associated with the generation of intracellular ROS, and this effect was reversed by pretreatment with N-acetyl cysteine. Chrysophanic acid-induced cell death was not associated with changes in apoptotic or necroptotic marker proteins. Conclusions: The cell death induced by chrysophanic acid resembled neither apoptotic nor necroptotic cell death in human renal cell carcinoma Caki-2 cells. PMID:27390736

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

    PubMed

    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

  6. Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future

    PubMed Central

    Pal, Sumanta K.

    2014-01-01

    At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

  7. Surgical considerations for patients with metastatic renal cell carcinoma.

    PubMed

    Adibi, Mehrad; Thomas, Arun Z; Borregales, Leonardo D; Matin, Surena F; Wood, Christopher G; Karam, Jose A

    2015-12-01

    Among patients with renal cell carcinoma (RCC), 25-30% present with metastatic disease at the time of initial diagnosis. Despite the ever-increasing array of treatment options available for these patients, surgery remains one of the cornerstones of therapy. Proper patient selection for cytoreductive surgery is paramount to its effective use in the management of patients with metastatic RCC despite the decrease in reported morbidity rates. We explore the evolving role cytoreductive surgery in metastatic RCC spanning the immunotherapy era to the targeted therapy era. Despite significant advances in the management of patients with metastatic RCC, further evidence on the definitive role of cytoreductive surgery in the targeted therapy era is awaited through large randomized trials. PMID:26546481

  8. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    PubMed Central

    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 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. PMID:26257975

  9. The somatic genomic landscape of chromophobe renal cell carcinoma

    PubMed Central

    Davis, Caleb F.; Ricketts, Christopher; 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

    Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations. PMID:25155756

  10. ASCO 2006 highlights: targeted therapy for renal cell carcinoma.

    PubMed

    Michaelson, M Dror

    2007-06-01

    In the past few years, advances in the understanding of the pathogenesis of renal cell carcinoma (RCC) have resulted in the identification of new therapeutic targets, and ultimately, the development of new targeted agents for the treatment of the disease. This paper reviews latest data in RCC for the recently approved agents sunitinib and sorafenib, as well as other molecularly targeted drugs, presented at the annual meeting of the American Society for Clinical Oncology, held in Atlanta, Georgia, in June 2006. Clinical findings to date show that these new agents are challenging the role of cytokines in this setting, and for some (e.g. sunitinib) a substantially improved efficacy profile (progression-free survival and response) over conventional cytokine therapy has been reported. While challenges remain with regard to optimal use of these agents, the outlook for patients with advanced RCC has improved considerably and there is great hope for continuing progress. PMID:17367939

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

    PubMed

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

    2014-09-01

    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 with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. PMID:25155756

  12. Serum and Urine Biomarkers for Human Renal Cell Carcinoma

    PubMed Central

    Pastore, A. L.; Palleschi, G.; Silvestri, L.; Moschese, D.; Ricci, S.; Petrozza, V.; Carbone, A.; Di Carlo, A.

    2015-01-01

    Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called “targeted therapies.” The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients. PMID:25922552

  13. A Rare Case of Renal Cell Carcinoma With Leiomyomatous Stroma and Concomitant Ruptured Adrenal Aneurysm.

    PubMed

    Lu, Chuanyong; Nicastri, Anthony; Shao, Charles

    2016-09-01

    Here we report a rare case of coexisting renal cell carcinoma (RCC) with leiomyomatous stroma and a ruptured adrenal aneurysm. The patient was a 75-year-old woman with acute abdominal pain. Imaging studies showed a left peri-renal hematoma and a mass in the left kidney. Left nephrectomy and adrenalectomy were performed. Pathological examination showed a ruptured aneurysm in the left adrenal gland. The renal mass was composed of tubules and acini of epithelial cells and a prominent leiomyomatous stroma. The tumor cells were positive for carbonic anhydrase IX, cytokeratin 7, and negative for AMACR, consistent with clear cell (tubulo) papillary RCC. PMID:27516974

  14. Restored expression levels of TET1 decrease the proliferation and migration of renal carcinoma cells

    PubMed Central

    FAN, MIN; HE, XIAOZHOU; XU, XIANLIN

    2015-01-01

    Renal carcinoma is the most common type of kidney cancer in adults and is responsible for ~90–95% of the cases of kidney cancer. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, and is expressed at low levels in multiple malignancies. In the present study, a series of experiments were designed and performed to investigate whether the expression of TET1 is clinically correlated with clinical outcomes in renal carcinoma, and to examine the associations between TET1 expression level and the proliferation and migration in renal carcinoma cells. As a result, TET1 was observed to exhibit markedly low expression levels in 54 tumor tissue samples from 54 patients with renal carcinoma. Furthermore, statistical analysis revealed a clinical correlation between low expression levels of TET1 and the prognosis of patients with renal carcinoma. When TET1 was overexpressed in renal carcinoma cells, the viability and invasive abilities of the cells were decreased, and the rate of apoptosis was increased. In conclusion, the results demonstrated that TET1 is involved in tumor inhibition in renal carcinoma by promoting cell apoptosis and inhibiting cell proliferation and invasion, which may be exploited as a novel therapeutic target in the treatment of renal carcinoma. PMID:26165803

  15. Stem cell technology for the treatment of acute and chronic renal failure

    PubMed Central

    Pino, Christopher J.; Humes, H. David

    2010-01-01

    Acute and chronic renal failure are disorders with high rates of morbidity and mortality. Current treatment is based upon conventional dialysis to provide volume regulation and small solute clearance. There is growing recognition that renal failure is a complex disease state requiring a multifactorial therapy to address the short-comings of the conventional monofactorial approach. Kidney transplantation remains the most effective treatment, however, organ availability lags far behind demand. Many key kidney functions including gluconeogenesis, ammoniagenesis, metabolism of glutathione, catabolism of important peptide hormones, growth factors, and cytokines critical to multiorgan homeostasis and immunomodulation are provided by renal tubule cells. Therefore, cell-based therapies are promising multifactorial treatment approaches. In this review, current stem cell technologies including adult stem cells, embryonic stem cells and induced pluripotent stem cells will be discussed as cell sources for the treatment of acute and chronic renal failure. PMID:20801413

  16. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation

    PubMed Central

    Chou, Hsiu-Chu; Chang, Chih-Cheng; Lo, Hau-Yin; Juan, Shu-Hui

    2016-01-01

    Perfluorinated chemicals (PFCs) are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS) caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs). In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1) by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP) assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α) by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE) in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation. PMID:27171144

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

    PubMed

    Wen, Li-Li; Lin, Chien-Yu; Chou, Hsiu-Chu; Chang, Chih-Cheng; Lo, Hau-Yin; Juan, Shu-Hui

    2016-01-01

    Perfluorinated chemicals (PFCs) are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS) caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs). In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1) by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP) assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α) by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE) in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation. PMID:27171144

  18. MicroRNA profiles classify papillary renal cell carcinoma subtypes

    PubMed Central

    Wach, S; Nolte, E; Theil, A; Stöhr, C; T Rau, T; Hartmann, A; Ekici, A; Keck, B; Taubert, H; Wullich, B

    2013-01-01

    Background: Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes. Methods: We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes. Results: Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes. Conclusion: MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling. PMID:23799849

  19. Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma

    PubMed Central

    Combe, Pierre; de Guillebon, Eleonore; Thibault, Constance; Granier, Clémence; Tartour, Eric; Oudard, Stéphane

    2015-01-01

    Despite the renaissance of cancer immunotherapy, no novel immunotherapy has been approved for the treatment of renal cell cancer (RCC) since the availability of recombinant cytokines (interleukin-2, interferon-α). All vaccine trials have failed to meet their endpoints although they have highlighted potential predictive biomarkers (e.g., pre-existing immune response, hematological parameters, tumor burden). Recent advances in immunomodulatory therapies have prompted the study of combination treatments targeting the tumor immunosuppressive microenvironment consisting of regulatory T-cells (Treg), myeloid suppressor cells, and cytokines. Approaches under investigation are use of inhibitors to curb the overexpression of immune checkpoint ligands by tumor cells (e.g., anti-CTLA-4, anti-PD-1/PD-L1) and exploiting the immunomodulatory effects of anti-angiogenic agents that are the current standard of metastatic RCC care. Phase III trials are focusing on the possible synergy between therapeutic vaccines (e.g., IMA-901 and AGS-003) and anti-angiogenic agents. PMID:26155388

  20. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.

    PubMed

    Lau, B H; Ruckle, H C; Botolazzo, T; Lui, P D

    1994-01-01

    Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities. PMID:7812364

  1. Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis.

    PubMed

    Williamson, Sean R; Kum, Jennifer B; Goheen, Michael P; Cheng, Liang; Grignon, David J; Idrees, Muhammad T

    2014-04-01

    A component of syncytial-type multinucleated tumor giant cells is uncommon in clear cell renal cell carcinoma, and the histogenesis, incidence, and clinical implications of this finding are not well understood. We retrieved 13 such tumors from our pathology archives in patients with a median age of 60years, comprising 1.5% of clear cell renal cell carcinomas. Stage was typically pT4 or pT3 (each 38%). Microscopically, all tumors included a component of low-grade clear cell renal cell carcinoma with usual features. Syncytial-type giant tumor cells possessed voluminous cytoplasm, usually granular and eosinophilic, and numerous nuclei similar to those of the mononuclear tumor cells. Transition between areas of mononuclear and multinucleated cells was sometimes abrupt. Other findings included necrosis (77%), hyaline globules (46%), emperipolesis (46%), and intranuclear cytoplasmic invaginations (23%). Immunohistochemical staining typically revealed both mononuclear and multinucleated cells to be positive for carbonic anhydrase IX, CD10, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3 and negative for β human chorionic gonadotropin, TFE3, cathepsin K, cytokeratin 7, cytokeratin 20, HMB45, CD68, smooth muscle actin, and S100. Most patients with available information (7/9) were alive with metastatic disease at the most recent follow-up. Syncytial-type giant cells are an uncommon finding associated with aggressive clear cell renal cell carcinomas. Despite the unusual appearance of this tumor component, its immunoprofile supports an epithelial lineage and argues against trophoblastic, osteoclast-like, or histiocytic differentiation. Reactivity for typical clear cell renal cell carcinoma antigens facilitates discrimination from giant cells of epithelioid angiomyolipoma or other tumors, particularly in a biopsy specimen or a metastatic tumor. PMID:24499686

  2. Renal cell carcinoma in South Korea: a multicenter study.

    PubMed

    Kim, Haeryoung; Cho, Nam Hoon; Kim, Dong-Sug; Kwon, Young-Mi; Kim, Eun Kyung; Rha, Seo Hee; Park, Yong Wook; Shim, Jung Weon; Lee, Sang Sook; Lee, Shi Nae; Lee, Juhie; Lee, Jin Sook; Lee, Tae-Jin; Jung, Soo Jin; Jung, Soon-Hee; Chung, Jin Haeng; Cho, Hyun Yee; Joo, Hee Jae; Choi, Yeong-Jin; Choi, Chan; Han, Woon Sup; Hur, Bang; Ro, Jae Y

    2004-12-01

    The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs. PMID:15619217

  3. Cytochrome P450 CYP3A in human renal cell cancer

    PubMed Central

    Murray, G I; McFadyen, M C E; Mitchell, R T; Cheung, Y-L; Kerr, A C; Melvin, W T

    1999-01-01

    Renal cell cancer is the main malignant tumour of the kidney and has an increasing incidence. This type of tumour has a poor prognosis and shows intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which consists of three closely related forms, is involved in the oxidative activation and deactivation of a variety of carcinogens and several anti-cancer drugs. In this study the presence and cellular localization of CYP3A has been investigated using a combination of immunohistochemistry, immunoblotting and reverse transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and corresponding normal kidney. CYP3A was consistently expressed in both renal call cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour cells and in normal kidney the predominant cellular localization of CYP3A was to proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7 mRNA were consistently present in both tumour and normal samples, while CYP3A4 mRNA was present in 65% of tumours and 90% of normal samples. This study indicates that individual members of the CYP3A family are expressed in renal cell cancer. The presence of CYP3A in renal cell cancer might be important in the metabolic potentiation as well as the detoxification of chemotherapeutic agents used to renal cancer. © 1999 Cancer Research Campaign PMID:10206301

  4. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma.

    PubMed

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A S; Ailles, Laurie E

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ(-/-) (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  5. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma

    PubMed Central

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  6. Renal small cell carcinoma (neuroendocrine carcinoma) without features of transitional cell carcinoma.

    PubMed

    Masuda, T; Oikawa, H; Yashima, A; Sugimura, J; Okamoto, T; Fujioka, T

    1998-05-01

    Seventeen cases of renal small cell carcinoma have been reported in the literature. Approximately half of the reported cases show combined features of transitional cell carcinoma. Presented herein is a case of renal small cell carcinoma in a 37-year-old Japanese male who had been treated for 10 years with famotidine for duodenal ulcer. He suffered from sudden-onset chest pain at presentation and myxoma of the right atrium was suspected. He was treated by atriotomy and a tumor was removed from the right atrium and pulmonary artery. Histological examination, however, revealed it to be small cell carcinoma. Accordingly, a radical operation was performed for the removal of a tumor found in the right kidney. Histological examination of the tumor confirmed the presence of renal small cell carcinoma without any features of transitional cell carcinoma. It is reported that long-term administration of an histamine 2 (H2) receptor antagonist may produce carcinoid tumors in rodents and enterochromaffin-like cell hyperplasia in humans. The possible relationship between neuroendocrine carcinoma and H2 receptor antagonist therapy is discussed. PMID:9704349

  7. lncRNA uc009yby.1 promotes renal cell proliferation and is associated with poor survival in patients with clear cell renal cell carcinomas

    PubMed Central

    Ren, Xingfeng; Lan, Tianbiao; Chen, Yan; Shao, Ziyun; Yang, Cheng; Peng, Jun

    2016-01-01

    The expression and function of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) remains unclear. The present study measured the expression profiles of three lncRNAs (uc009yby.1, ENST00000514034, and ENST00000450687) using reverse transcription-quantitative polymerase chain reaction, and assessed their signatures in distinguishing ccRCC from matched normal tissues via analysis of receiver operating characteristic (ROC) curves. The expression of uc009yby.1 was inhibited by transfection of renal cells with small interfering RNA, and then the cell proliferation was evaluated by using a Cell Counting Kit-8. The results showed that the expressions of uc009yby.1 and ENST00000514034 were markedly increased in ccRCC compared with the matched normal tissues (P<0.0001 and P=0.0008, respectively), whereas the ENST00000450687 expression was not significantly altered. ROC curves yielded an area under the curve (AUC) value of 0.7000 for uc009yby.1, with sensitivity of 54.29% and specificity of 82.86%; and an AUC value of 0.6627 for ENST00000514034, with sensitivity of 60.00% and specificity of 67.14%. Furthermore, knockdown of uc009yby.1 suppressed renal cell proliferation (Day 0, P=0.7844; Day 1, P=0.0018; Day 2, P=0.0001; Day 3, P<0.000; Day 4, P<0.0001). Taken together, these findings suggest that the expression profiles of uc009yby.1 and ENST00000514034 may serve as novel biomarkers for ccRCC detection, and that uc009yby.1 is strongly associated with renal cell proliferation. PMID:27602119

  8. Extramedullary hematopoiesis within cystic renal cell carcinoma with oncocytic and chromophobe cell types: A case report

    PubMed Central

    CELIK, BETUL; BULUT, TANGUL; SEDELE, MURAT; SEZER, CEM; KARAKUS, VOLKAN

    2014-01-01

    Extramedullary hematopoiesis (EMH) is a phenomenon in which hematopoietic cells are found in sites other than the bone marrow. It is usually observed in the liver and spleen but may occasionally be found within solid tumors. The current case report presents a 69-year-old female patient who presented with a renal cyst. Histopathological examination following surgical removal of the cyst revealed a lining of oncocytic- and chromophobe-type cells with capsular invasion and a mass forming EMH with evident bone trabeculae within the cyst wall. Circulating hematopoietic stem cells in the blood and their colonization within tissues is discussed in the present case report, emphasizing certain types of renal cell carcinoma. PMID:24520308

  9. Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Saito, Kosuke; Arai, Eri; Maekawa, Keiko; Ishikawa, Masaki; Fujimoto, Hiroyuki; Taguchi, Ryo; Matsumoto, Kenji; Kanai, Yae; Saito, Yoshiro

    2016-01-01

    Renal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles of clear cell RCC (ccRCC), a major RCC subtype, by performing a lipidomic analysis of specimens of cancerous tissue and the surrounding normal renal cortex obtained from the same patients (N = 49). We also compared the lipidomic profiles with the lipogenic transcriptome of specimens of cancerous tissue and the surrounding normal renal cortex for an additional set of patient samples (N = 95). Overall, we detected 326 lipids, including phospholipids, sphingolipids, neutral lipids, and eicosanoids. The levels of more than 70% of the detected lipids were significantly different (P < 0.01, corrected by the false discovery rate). The cancerous tissue was distinguished by higher levels of ether-type phospholipids, cholesterol esters, and triacylglycerols, as well as by lower levels of phospholipids (except for phosphatidylcholines) and polyunsaturated fatty acids. Characteristic changes in the levels of mRNAs and metabolites suggested that the phosphatidylethanolamine (PE) synthesis pathway is suppressed in ccRCC and associated with cell proliferation. The present study represents the lipidomic profiles of ccRCC, which provides novel information about the metabolic changes in renal cancerous tissue and RCC pathophysiology. PMID:27357243

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

    SciTech Connect

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming . E-mail: fandaim@fmmu.edu.cn

    2007-05-18

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to {beta}-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing {beta}-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells.

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

    PubMed Central

    2013-01-01

    Background Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL) patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney. Methods We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential. Results Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient. Cilia frequencies in a total of

  12. Human embryonic mesenchymal stem cells participate in differentiation of renal tubular cells in newborn mice

    PubMed Central

    Yuan, Li; Liu, Hou-Qi; Wu, Min-Juan

    2016-01-01

    Stem cells are used with increasing success in the treatment of renal tubular injury. However, whether mesenchymal stem cells (MSC) differentiate into renal tubular epithelial cells remains controversial. The aims of the present study were to observe the localization of human embryonic MSCs (hMSCs) in the kidneys of newborn mice, and to investigate hMSC differentiation into tubular epithelium. Primary culture hMSCs were derived from 4–7-week-old embryos and labeled with the cell membrane fluorescent dye PKH-26. The degree of apoptosis, cell growth, differentiation and localization of hMSCs with and without this label were then determined using immunohistochemical methods and flow cytometry. hMSCs and PKH26-labeled hMSCs were revealed to differentiate into chondrocytes and adipocytes, and were demonstrated to have similar proliferative capability. In the two cell types, the antigens CD34 and CD45, indicative of hematopoietic lineages, were not expressed; however, the expression of the mesenchymal markers CD29 and CD90 in MSCs, was significantly increased. During a 4-week culture period, laser confocal microscopy revealed that PKH26-labeled hMSCs in the kidneys of newborn mice gradually dispersed. Two weeks after the injection of the PKH26-labeled cells, the percentage of PKH26-labeled hMSCs localized to the renal tubules was 10±2.1%. In conclusion, PKH26 labeling has no effect on hMSC differentiation, proliferation and mesenchymal cell surface features, and hMSCs injected into the kidneys of newborn mice may transform to renal tubule epithelium. PMID:27446255

  13. Clear cell papillary renal cell carcinoma: a clinicopathological study emphasizing ultrastructural features and cytogenetic heterogeneity.

    PubMed

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

    2013-01-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC. PMID:24294381

  14. Embolization for Treatment of Gastrointestinal Hemorrhage Secondary to Recurrent Renal Cell Carcinoma

    SciTech Connect

    Kobak, Jeff; Gandras, Eric J. Fleury, Linwald; Macura, Jerzy; Shams, Joseph

    2006-12-15

    Massive gastrointestinal hemorrhage secondary to metastatic renal cell carcinoma involving the jejunum is rare but has been previously described in the medical literature. Treatment options for metastatic renal cell carcinoma are limited, but transcatheter arterial embolization can be performed to control gastrointestinal hemorrhage either alone or prior to surgical resection. We describe a case of successful transcatheter arterial embolization for control of massive gastrointestinal hemorrhage secondary to locally recurrent renal cell carcinoma invading the jejunum and review the literature. Arteriography provided both the diagnosis of recurrent disease and the means of therapy.

  15. Primary Malignant Melanoma of Renal Pelvis with Extensive Clear Cell Change

    PubMed Central

    Liapis, George; Sarlanis, Helen; Poulaki, Elpida; Stravodimos, Konstandinos; Lazaris, Andreas C

    2016-01-01

    Our presentation illustrates a rare case of primary renal pelvis malignant melanoma in a 35-year-old man. The diagnosis of malignant melanoma was based on immunophenotype and the detection of intracellular melanin pigment. The renal origin was proven by the presence of scattered melanocytes within the urothelium of the pelvis. The tumor exhibited extensive clear cell change that closely mimics clear cell renal cell carcinoma. The patient’s clinical history did not disclose any signs of previous melanocytic skin or mucosa lesions. Differential diagnosis includes tumors capable of synthesizing melanin or expressing melanocytic markers. PMID:27226943

  16. A Rare Intrascrotal Metastases From Renal Cell Carcinoma: A Case Report

    PubMed Central

    Adawi, Essa

    2015-01-01

    Metastatic renal cell carcinoma is potentially a lethal disease with in some cases aggressive behavior. The given fact that the patterns of metastases from RCC are not clearly identified, which may involve some rare metastatic locations. We present a case of 58 years old male presented with painless left scrotal mass, which was discovered to be an intrascrotal metastases appeared 3 years after nephrectomy for ipsilateral renal cell carcinoma. We believe that the rarity of the metastatic site and the intriguing possible mechanism of spread make an interesting case for clinicians and could add more follow-up measures for patients treated from renal cell carcinoma. PMID:26793583

  17. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis

    PubMed Central

    Cruz, Iluminado A.; Hosten, Adrian O.; Dillard, Martin G.; Castro, Oswaldo L.

    1982-01-01

    Advanced renal failure occurred in nine adult sickle cell disease patients. There were six men and three women with a mean age of 38.6 years. Eight patients had homozygous SS disease, one had sickle cell thalassemia. Three patients had acute renal failure from which they partially recovered. Six developed endstage kidney disease requiring dialysis. Two of these received a kidney transplant, and there was one death in the immediate postoperative period. Angina pectoris, hyperkalemia, and severe anemia complicated chronic dialysis, suggesting that early transplantation should be considered for sickle cell anemia patients with renal failure. PMID:6757451

  18. Decreased expression of mucin 18 is associated with unfavorable postoperative prognosis in patients with clear cell renal cell carcinoma

    PubMed Central

    Bai, Qi; Liu, Li; Long, Qilai; Xia, Yu; Wang, Jiajun; Xu, Jiejie; Guo, Jianming

    2015-01-01

    Background: MUC18 is correlated with tumor progression and metastasis in types of malignancy. But the role of MUC18 in clear cell renal cell carcinoma remains unclear. In this study, we aimed to investigate the expression of MUC18 and its correlation with clinical outcomes in clear cell renal cell carcinoma. Patients and Methods: Immunohistochemical staining was performed in samples from 288 patients with clear cell renal cell carcinoma. We used Kaplan-Meier method and Cox proportional hazard models to value the association between MUC18 expression and clinical outcome. Nomogram was constructed to predict overall survival at 5 and 8 years after nephrectomy. Results: MUC18 expression was significantly decreased in tumor compared to non-tumor tissue (P<0.001). Lower MUC18 expression in tumor predicted a shorter survival time (P=0.007). By multivariate cox analysis, MUC18 was defined as an independent prognostic factor (P=0.006). The nomogram performed better in predicting 5- and 8-year overall survival than the TNM stage alone in clear cell renal cell carcinoma. Conclusion: MUC18 is an independent prognostic factor for clear cell renal cell carcinoma and could be incorporated with the other parameters to predict 5- and 8-year overall survival for clear cell renal cell carcinoma patients. PMID:26617818

  19. Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

    PubMed Central

    Sallustio, Fabio; Serino, Grazia; Schena, Francesco Paolo

    2015-01-01

    Abstract Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133+/CD24+ cells, with a view to a future application of these cells for the treatment of acute renal injury. PMID:26309808

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

    PubMed

    Kanesvaran, Ravindran; Tan, Min-Han

    2014-01-01

    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. PMID:24737951

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

    PubMed Central

    Kanesvaran, Ravindran; Tan, Min-Han

    2014-01-01

    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. PMID:24737951

  2. Renal arteriography

    MedlinePlus

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Update Date 4/7/2014 Updated by: Jason ... Failure Kidney Tests X-Rays Browse the Encyclopedia A. ...

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

    PubMed

    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. PMID:23909823

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

    MedlinePlus

    ... Pelvis and Ureter Treatment (PDQ®)–Patient Version General Information About Transitional Cell Cancer of the Renal Pelvis ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

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

    PubMed

    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

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

    PubMed Central

    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

  7. Usefulness of resistive index on spectral Doppler ultrasonography in the detection of renal cell carcinoma in patients with end-stage renal disease

    PubMed Central

    2014-01-01

    Purpose: The aim of this study was to explore the usefulness of the resistive index (RI) on spectral Doppler ultrasonography (US) in the detection of renal cell carcinoma (RCC) in patients with end-stage renal disease (ESRD). Methods: Seventeen ESRD patients with kidneys in which renal masses were suspected in routine US were subjected. They underwent computed tomography scans and additional Doppler US for the characterization of the detected lesions. All underwent radical nephrectomy with the suspicion of RCC. Fourteen patients finally were included. RI measurements were conducted in the region of the suspected renal mass and the background renal parenchyma. The intraclass correlation coefficient was used to assess the reproducibility of the RI measurement. A paired t-test was used to compare the RI values between the renal mass and the background renal parenchyma (P<0.05). Results: The RI values measured at the RCCs were significantly lower than those measured at the background renal parenchyma (0.41-0.65 vs. 0.75-0.89; P<0.001). The intrareader reproducibility proved to be excellent and good for the renal masses and the parenchyma, respectively (P<0.001). Conclusion: RI on spectral Doppler US is useful in detecting RCC in patients with ESRD. The RI values measured at the RCCs were significantly lower than those measured at the background renal parenchyma. PMID:24936507

  8. Foci of Entotic Nuclei in Different Grades of Noninherited Renal Cell Cancers.

    PubMed

    Kong, Yuke; Liang, Yaojun; Wang, Jianqin

    2015-02-01

    We report here an intriguing pattern in nuclear appearance of renal clear cell cancer. In low grade clear cell cancer, detailed examination showed that in many cells, two or more nuclei were within the confines of a single cell membrane. This likely resulted from a cell being contained within its neighboring cell. Consequently, this resulted in appearance of multicellularity. This appearance of the nuclei were not associated with mitotic figures, suggesting that these did not result from nuclear fission. Additionally, the cells containing this nuclei did not show any evidence of cytokinesis including equatorial tapering, suggesting that the process may have resulted from cytokinesis failure. In some sections of higher grade clear cell cancer, these appearance were higher, though we did not observe any frank syncytium formation. On careful observation, there were isolated events of fusion of nuclei within a single cell in different grades of renal cell cancers. There occurrence was more frequent in higher grades of clear cell renal cancer and metastatic clear cell carcinoma. These features were also demonstrable in multiple fields of lower grades of clear cell carcinoma. This phenomenon of entosis may contribute to aneuploidy and tumor progression to dysplastic stages and genomic instability in renal cancers. Future studies are aimed at delineating the cell-cell boundaries and the mechanism contributing to this observation, either from peripheral cell engulfing or failure of cytosolic division for cell separation. PMID:25855323

  9. Imaging Findings of Common Benign Renal Tumors in the Era of Small Renal Masses: Differential Diagnosis from Small Renal Cell Carcinoma: Current Status and Future Perspectives

    PubMed Central

    Woo, Sungmin

    2015-01-01

    The prevalence of small renal masses (SRM) has risen, paralleling the increased usage of cross-sectional imaging. A large proportion of these SRMs are not malignant, and do not require invasive treatment such as nephrectomy. Therefore, differentation between early renal cell carcinoma (RCC) and benign SRM is critical to achieve proper management. This article reviews the radiological features of benign SRMs, with focus on two of the most common benign entities, angiomyolipoma and oncocytoma, in terms of their common imaging findings and differential features from RCC. Furthermore, the role of percutaneous biopsy is discussed as imaging is yet imperfect, therefore necessitating biopsy in certain circumstances to confirm the benignity of SRMs. PMID:25598678

  10. USE OF THE SPONTANEOUS TSC2 KNOCKOUT (EKER) RAT MODEL OF HEREDITARY RENAL CELL CARCINOMA FOR THE STUDY OF RENAL CARCINOGENS

    EPA Science Inventory

    The kidney is a frequent site for chemically induced cancers in rodents and among the ten most frequent sites for cancer in human patients. Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. He...

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

    PubMed Central

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

    2014-01-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or “reperfusion” of renal proximal tubular cells (RPTCs) after ATP-depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP-depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. PMID:24726884

  12. Symptomatic cardiac metastasis responding to pazopanib in a patient with renal cell carcinoma.

    PubMed

    Behzadigohar, Ramin; Rosenthal, Mark A; Tran, Ben

    2015-06-01

    We report a case of an 82-year-old man with renal cell carcinoma who developed a cardiac metastasis within the interventricular septum. He had been under watchful waiting for indolent metastatic renal cell carcinoma for many years before developing symptoms consistent with heart failure. At this time, a 44 mm interventricular septal mass, consistent with a cardiac metastasis, was identified as the cause of his symptoms. Pazopanib was initiated which led to both a clinical and radiological response. PMID:26068633

  13. Computational Modelling of Metastasis Development in Renal Cell Carcinoma

    PubMed Central

    Baratchart, Etienne; Benzekry, Sébastien; Bikfalvi, Andreas; Colin, Thierry; Cooley, Lindsay S.; Pineau, Raphäel; Ribot, Emeline J; Saut, Olivier; Souleyreau, Wilfried

    2015-01-01

    The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions. PMID:26599078

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

    PubMed

    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

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

    PubMed Central

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

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

  16. Proteases in renal cell death: calpains mediate cell death produced by diverse toxicants.

    PubMed

    Schnellmann, R G; Williams, S W

    1998-09-01

    The role of proteases in renal cell death has received limited investigation. Calpains are non-lysosomal cysteine proteases that are Ca+2 activated. Calpain inhibitors that block the active site of calpains (calpain inhibitor 1 and 2) or the Ca+2 binding domain of calpains (PD150606) decreased calpain activity in rabbit renal proximal tubule (RPT) suspensions. The inhibition of calpain activity decreased cell death produced by the diverse toxicants antimycin A (mitochondrial inhibitor), tetrafluroethyl-L-cysteine (nephrotoxic halocarbon), bromohydroquinone (nephro-toxic quinone), t-butylhydroperoxide (model oxidant) and ionomycin (Ca+2 ionophore). In summary, calpains appear to play a common and critical role in cell injury produced by diverse toxicants with different mechanisms of action. The general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido (4-guanidino)-butane (E-64) decreased antimycin A- and tetrafluoroethyl-L-cysteine-induced cell death but had no effect on bromohydroquinone- or t-butylhydroperoxide-induced cell death. Serine/cysteine protease inhibitors (antipain, leupeptin) were not cytoprotective to RPT exposed to any of the toxicants. The cytoprotection associated with E-64 correlated with inhibition of lysosomal cathepsins and E-64 was only cytoprotective after some cell death had occurred. Since some cell death occurred prior to the E-64 cytoprotective effect, lysosomal cathepsins may be released from dying cells and subsequently target the remaining viable cells. PMID:9768434

  17. Fluid intake and incidence of renal cell carcinoma in UK women

    PubMed Central

    Allen, N E; Balkwill, A; Beral, V; Green, J; Reeves, G

    2011-01-01

    Background: It has been suggested that the apparent protective effect of alcohol intake on renal cell carcinoma may be due to the diluting effect of carcinogens by a high total fluid intake. We assessed the association between intakes of total fluids and of specific beverages on the risk of renal cell carcinoma in a large prospective cohort of UK women. Methods: Information on beverage consumption was obtained from a questionnaire sent ∼3 years after recruitment into the Million Women Study. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for renal cell carcinoma associated with beverage consumption adjusted for age, region of residence, socioeconomic status, smoking, and body mass index. Results: After an average of 5.2 years of follow-up, 588 cases of renal cell carcinoma were identified among 779 369 women. While alcohol intake was associated with a reduced risk of renal cell carcinoma (RR for ⩾2 vs <1 drink per day: 0.76; 95% CI: 0.61–0.96; P for trend=0.02), there was no association with total fluid intake (RR for ⩾12 vs <7 drinks per day: 1.15; 95% CI: 0.91–1.45; P for trend=0.3) or with intakes of specific beverages. Conclusions: The apparent protective effect of alcohol on the risk of renal cell carcinoma is unlikely to be related to a high fluid intake. PMID:21407222

  18. Sunitinib re-challenge in advanced renal-cell carcinoma

    PubMed Central

    Porta, C; Paglino, C; Grünwald, V

    2014-01-01

    Despite offering significant clinical benefits in advanced renal-cell carcinoma (RCC), the effectiveness of targeted therapies eventually declines with the development of resistance. Defining optimal sequences of therapy is therefore the focus of much current research. There is also evidence that treatment ‘re-challenge' may be an effective strategy in some patients. We review evidence to evaluate whether sunitinib may have value as re-challenge therapy in patients who have progressed on prior targeted therapy with sunitinib and/or an alternative tyrosine kinase inhibitor or mammalian target of rapamycin inhibitor. Re-challenge with sunitinib appears to be of clinical benefit, thus representing a feasible therapeutic option for patients with advanced RCC who are refractory to other treatments and are able to receive further therapy. These observations support hypotheses that resistance to targeted agents is transient and can be at least partially reversed by re-introduction of the same agent after a treatment break. Median progression-free survival durations appear to be shorter and response rates lower on re-challenge than following initial treatment, although a wider interval between treatments appears to increase response to sunitinib re-challenge. PMID:24800947

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

    PubMed Central

    Raman, Rachna; Vaena, Daniel

    2015-01-01

    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. PMID:26161397

  20. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

    PubMed Central

    Santoni, Matteo; Amantini, Consuelo; Burattini, Luciano; Berardi, Rossana; Santoni, Giorgio; Cascinu, Stefano; Muzzonigro, Giovanni

    2013-01-01

    Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents. PMID:24093097

  1. Renal Cell Carcinoma: Molecular Biology and Targeted Therapy

    PubMed Central

    Su, Daniel; Stamatakis, Lambros; Singer, Eric A.; Srinivasan, Ramaprasad

    2014-01-01

    Purpose of review Renal cell carcinoma (RCC) continues to be the subject of vigorous clinical and translational investigation. Advances in systemic targeted therapies, new molecular pathways, and immunotherapy approaches will be discussed. Recent findings Agents targeting the vascular endothelial growth factor (VEGF) and/or the mammalian target of rapamycin (mTOR) pathways continue to be the mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity has improved the toxicity profile associated with newer VEGF-pathway antagonists, durable complete responses remain the exception. Identification of novel pathways/agents, as well as the optimal sequencing and combination of existing targeted agents, remain areas of active study. In addition, emerging data from early clinical trials has reinvigorated interest in immunomodulatory agents. Summary The therapeutic armamentarium available to genitourinary oncologists continues to grow but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC. PMID:24675233

  2. [Succinate dehydrogenase (SDH)-deficient renal cell carcinoma].

    PubMed

    Agaimy, A

    2016-03-01

    Succinate dehydrogenase (SDH) represents a type II mitochondrial complex related to the respiratory chain and Krebs cycle. The complex is composed of four major subunits, SDHA, SDHB, SDHC and SDHD. The oncogenic role of this enzyme complex has only recently been recognized and the complex is currently considered an important oncogenic signaling pathway with tumor suppressor properties. In addition to the familial paraganglioma syndromes (types 1-5) as prototypical SDH-related diseases, many other tumors have been defined as SDH-deficient, in particular a subset of gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, a subset of pancreatic neuroendocrine neoplasms (recently added) and a variety of other tumor entities, the latter mainly described as rare case reports. As a central core subunit responsible for the integrity of the SDH complex, the expression of SDHB is lost in all SDH-deficient neoplasms irrespective of the specific SDH subunit affected by a genetic mutation in addition to concurrent loss of the subunit specifically affected by genetic alteration. Accordingly, all SDH-deficient neoplasms are by definition SDHB-deficient. The SDH-deficient renal cell carcinoma (RCC) has only recently been well-characterized and it is included as a specific subtype of RCC in the new World Health Organization (WHO) classification published in 2016. In this review, the major clinicopathological, immunohistochemical and genetic features of this rare disease entity are presented and discussed in the context of the broad differential diagnosis. PMID:26979428

  3. Stability of preclinical models of aggressive renal cell carcinomas.

    PubMed

    Varna, Mariana; Bousquet, Guilhem; Ferreira, Irmine; Goulard, Marie; El-Bouchtaoui, Morad; Artus, Pierre Mongiat; Verine, Jérome; de Kerviler, Eric; Hernandez, Lucie; Leboeuf, Christophe; Escudier, Bernard; Legrès, Luc; Setterblad, Niclas; Soliman, Hany; Feugeas, Jean-Paul; Janin, Anne; Bertheau, Philippe

    2014-01-01

    Renal-cell carcinomas (RCC) are often resistant to conventional cytotoxic agents. Xenograft models are used for in vivo preclinical studies and drug development. The validity of these studies is highly dependent on the phenotypic and genotypic stability of the models. Here we assessed the stability of six aggressive human RCC xenografted in nude/NMRI mice. We compared the initial samples (P0), first (P1) and fifth (P5) passages for the following criteria: histopathology, immunohistochemistry for CK7, CD10, vimentin and p53, DNA allelic profiles using 10 microsatellites and CGH-array. Next we evaluated the response to sunitinib in primary RCC and corresponding xenografted RCC. We observed a good overall stability between primary RCC and corresponding xenografted RCC at P1 and P5 regarding histopathology and immunohistochemistry except for cytokeratin 7 (one case) and p53 (one case) expression. Out of 44 groups with fully available microsatellite data (at P0, P1 and P5), 66% (29 groups) showed no difference from P0 to P5 while 34% (15 groups) showed new or lost alleles. Using CGH-array, overall genomic alterations at P5 were not different from those of initial RCC. The xenografted RCC had identical response to sunitinib therapy compared to the initial human RCC from which they derive. These xenograft models of aggressive human RCC are clinically relevant, showing a good histological and molecular stability and are suitable for studies of basic biology and response to therapy. PMID:25031714

  4. Potential Approaches and Recent Advances in Biomarker Discovery in Clear-Cell Renal Cell Carcinoma

    PubMed Central

    Majer, Weronika; Kluzek, Katarzyna; Bluyssen, Hans; Wesoły, Joanna

    2015-01-01

    The early diagnosis and monitoring of clear-cell Renal Cell Carcinoma (ccRCC), which is the most common renal malignancy, remains challenging. The late diagnosis and lack of tools that can be used to assess the progression of the disease and metastasis significantly influence the chance of survival of ccRCC patients. Molecular biomarkers have been shown to aid the diagnosis and disease monitoring for other cancers, but such markers are not currently available for ccRCC. Recently, plasma and serum circulating nucleic acids, nucleic acids present in urine, and plasma and urine proteins gained interest in the field of cancer biomarker discovery. Here, we describe the applicability of plasma and urine nucleic acids as cancer biomarkers with a particular focus on DNA, small RNA, and protein markers for ccRCC. PMID:26516358

  5. CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells.

    PubMed

    Liu, Xuejiao; Chong, Yulong; Liu, Huize; Han, Yan; Niu, Mingshan

    2016-03-01

    Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy. PMID:26937212

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

    PubMed

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

    2012-03-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient. PMID:22086304

  7. [Hereditary leiomyomatosis and renal cell cancer - HLRCC/multiple cutaneous and uterine leimomyomatosis - MCUL].

    PubMed

    Plevová, P; Hladíková, A; Tesařová, M

    2012-01-01

    Hereditary leiomyomatosis and renal cell cancer / multiple cutaneous and uterine leimomyomatosis is a relatively rare autosomal dominant condition which predisposes to the development of cutaneous and uterine leiomyomas and early-onset renal cell carcinoma, typically papillary carcinoma type II. It is caused by germline mutations in the FH gene encoding the fumarate hydratase enzyme. The test of fumarate hydratase activity in lymphocytes may be used as a screening method with subsequent mutation analysis of the FH gene in persons with reduced enzyme activity. Persons with this syndrome should be followed to detect any occurrence of these diseases. Treatment of renal cancer associated with the hereditary leiomyomatosis and renal cell cancer syndrome should be radical with respect to its aggressive nature. PMID:22920208

  8. Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode

    PubMed Central

    Sun, X-Y; Gan, Q-Z; Ouyang, J-M

    2015-01-01

    The cytotoxicity of calcium oxalate (CaOx) in renal epithelial cells has been studied extensively, but the cell death mode induced by CaOx with different physical properties, such as crystal size and crystal phase, has not been studied in detail. In this study, we comparatively investigated the differences of cell death mode induced by nano-sized (50 nm) and micron-sized (10 μm) calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) to explore the cell death mechanism. The effect of the exposure of nano-/micron-sized COM and COD crystals toward the African green monkey renal epithelial (Vero) cells were investigated by detecting cell cytoskeleton changes, lysosomal integrity, mitochondrial membrane potential (Δψm), apoptosis and/or necrosis, osteopontin (OPN) expression, and malondialdehyde (MDA) release. Nano-/micron-sized COM and COD crystals could cause apoptosis and necrosis simultaneously. Nano-sized crystals primarily caused apoptotic cell death, leading to cell shrinkage, phosphatidylserine ectropion, and nuclear shrinkage, whereas micron-sized crystals primarily caused necrotic cell death, leading to cell swelling and cell membrane and lysosome rupture. Nano-sized COM and COD crystals induced much greater cell death (sum of apoptosis and necrosis) than micron-sized crystals, and COM crystals showed higher cytotoxicity than the same-sized COD crystals. Both apoptosis and necrosis could lead to mitochondria depolarization and elevate the expression of OPN and the generation of lipid peroxidation product MDA. The amount of expressed OPN and generated MDA was positively related to cell injury degree. The physicochemical properties of crystals could affect the cell death mode. The results of this study may provide a basis for future studies on cell death mechanisms. PMID:27551481

  9. Loss of PBRM1 and BAP1 Expression Is Less Common in Non–Clear Cell Renal Cell Carcinoma Than in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Ho, Thai H.; Kapur, Payal; Joseph, Richard W.; Serie, Daniel J.; Eckel-Passow, Jeanette E.; Parasramka, Mansi; Cheville, John C.; Wu, Kevin J.; Frenkel, Eugene; Rakheja, Dinesh; Stefanius, Karoliina; Brugarolas, James; Parker, Alexander S.

    2014-01-01

    Background Recurrent mutations in polybromo-1 (PBRM1, ~40%) and BRCA1-associated protein-1 (BAP1, ~10%) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non clear cell renal cell carcinoma (non-ccRCC) or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC) and RO tumors using an immunohistochemistry (IHC) assay for which negative staining associates with loss-of-function mutations. Methods We identified 458 patients treated surgically for ccRCC, pRCC, chRCC and RO between 2004 and 2012. We performed IHC assays to evaluate PBRM1 and BAP1 protein expression to classify tumors as PBRM1- or BAP1-negative. We compared loss of staining of these 2 proteins in ccRCC and non-ccRCC using Fisher’s exact test. Results For the total cohort of 458 patients, we successfully stained both PBRM1 and BAP1 in 408 tumor samples. Consistent with the mutation rate, loss of PBRM1 and BAP1 staining occurred in 43% (80/187) and 10% (18/187) of ccRCC respectively. However, loss of PBRM1 staining occurred in only 3% (2/59), 6% (1/17) and 0% (0/34) of pRCC, chRCC and RO tumors, respectively (P<0.0001). BAP1 loss was not observed in any of the pRCC (N=61), chRCC (N=17) or RO (N=34) tumors (P=.00021). Conclusion Our data suggest that biallelic inactivation of PBRM1 or BAP1 is less common in non-ccRCC when compared to ccRCC tumors. These findings suggest that loss of PBRM1 or BAP1 are key events in ccRCC, whereas other pathways may support tumorigenesis in non-ccRCC subtypes. PMID:25465300

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

    PubMed Central

    Hu, Yanchun; Luo, Biao; Wu, Lei; Qiao, Yan; Mo, Quan; Xu, Ruiguang; Zhou, Yancheng; Ren, Zhihua; Zuo, Zhicai; Deng, Junliang; Peng, Guangneng; He, Wei; Wei, Yahui

    2015-01-01

    The cytotoxicity effects of E. adenophorum on cell cycle and apoptosis of renal cells in Saanen goat was evaluated by TUNEL, DAPI, AO/EB staining, DNA fragmentation assay, Caspase activity, Western-blot, qRT-PCR and flow cytometry analysis. 16 saanen goats randomly divided into four groups were fed on 0%, 40%, 60% and 80% E. adenophorum diets. The Results showed that E. adenophorum induced typical apoptotic features of renal cells. E. adenophorum significantly suppressed renal cells viability, caused cell cycle activity arrest and induced typical apoptotic features in a dose-dependent manner. However, the protein levels of Fas/FasL, Bid and caspase-8 did not appear significant changes in the process of E. adenophorum-induced apoptosis. Moreover, E. adenophorum administration slightly decreased Bcl-2 expression, promoted Bax translocation to mitochondria, triggered the release of Cyt c from mitochondria into cytosol and activated caspase-9, -3, and cleaved PARP. The mitochondrial p53 translocation was significantly activated, accompanied by a significant increase in the loss of ΔΨm, Cyt c release and caspase-9 activation. Above all, these data suggest that E. adenophorum induces renal cells apoptosis via the activation of mitochondria-mediated apoptosis pathway in renal cells. These findings may provide new insights to understand the mechanisms involved in E. adenophorum-caused cytotoxicity of renal cells. PMID:26382060

  11. Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue: Possible Role in Incipient Renal Fibrosis

    PubMed Central

    Müller, Claudia A.; Tampe, Björn; Ćirović, Sanja; Vještica, Jelena; Tomanović, Nada; Zeisberg, Michael; Müller, Gerhard A.

    2015-01-01

    Rare neural cell adhesion molecule (NCAM) positive cells have been previously described within the normal human adult kidney interstitium, speculating that they could increase in the interstitium with incipient interstitial renal fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney diseases, NCAM+ interstitial cells were detected in 62.4% cases. An increased number of NCAM+ cells was significantly observed only in incipient IRF compared to normal renal tissues and advanced IRF stages (p<0.001), independently of underlying diseases (p = 0.657). All three major NCAM isoforms’ RT-PCR bands were visible either in normal or in kidneys with incipient IRF, albeit their mRNA expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure NCAM+ cells population, obtained by laser capture microdissection, significant mRNA over-expression of NCAM140kD isoform was found in NCAM+ cells within incipient IRF (p = 0.004), while NCAM120kD and NCAM180kD isoforms were not changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously, qRT-PCR also showed significant αSMA (p = 0.014) and SLUG (p = 0.004) mRNAs up-regulation within the NCAM+ cells of incipient IRF, as well as highly decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036; respectively). However, using double immunofluorescence MMP-9 could still be detectable on the protein level in rare NCAM+ cells within the incipient IRF. Further characterization of NCAM+ cells by double immunofluorescent labeling revealed their association with molecules involved in fibrosis. Fibroblast growth factor receptor 1 (FGFR1) and α5β1 integrin were extensively expressed on NCAM+ cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4) was found to be present in few NCAM+ cells of both normal and interstitium with incipient fibrosis. Heterogeneity of NCAM+ interstitial cells in normal and incipient IRF, concerning molecules related to

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

    PubMed

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

    2009-07-01

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

  13. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

    PubMed Central

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

    2009-01-01

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

  14. Array comparative genomic hybridization identifies a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer.

    PubMed

    Koski, Taru A; Lehtonen, Heli J; Jee, Kowan J; Ninomiya, Shinsuke; Joosse, Simon A; Vahteristo, Pia; Kiuru, Maija; Karhu, Auli; Sammalkorpi, Heli; Vanharanta, Sakari; Lehtonen, Rainer; Edgren, Henrik; Nederlof, Petra M; Hietala, Marja; Aittomäki, Kristiina; Herva, Riitta; Knuutila, Sakari; Aaltonen, Lauri A; Launonen, Virpi

    2009-07-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome with cutaneous and uterine leiomyomatosis as well as renal cell cancer (RCC) as its clinical manifestations. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (fumarase) gene. In this study, we used array comparative genomic hybridization to identify the specific copy number changes characterizing the HLRCC-associated RCCs. The study material comprised formalin-fixed paraffin-embedded renal tumors obtained from Finnish patients with HLRCC. All 11 investigated tumors displayed the papillary type 2 histopathology typical for HLRCC renal tumors. The most frequent copy number changes detected in at least 3/11 (27%) of the tumors were gains in chromosomes 2, 7, and 17, and losses in 13q12.3-q21.1, 14, 18, and X. These findings provide genetic evidence for a distinct copy number profile in HLRCC renal tumors compared with sporadic RCC tumors of the same histopathological subtype, and delineate chromosomal regions that associate with this very aggressive form of RCC. PMID:19373782

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

    PubMed

    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

  16. T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment.

    PubMed

    Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann; von Vietinghoff, Sibylle

    2016-06-01

    Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe(-/-) (apolipoprotein E) CX3CR1(-/-) mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor-deficient (LDLr(-/-)) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1(-/-) bone marrow into LDLr(-/-) mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b(+)CD11c(+) myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1(-/-) splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr(-/-) mice, CX3CR1(+/-) T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1(-/-) T cells did not. Transfer of CX3CR1(+/-) but not Il17a(-/-) T cells into LDLr(-/-)CX3CR1(-/-) mice increased aortic lesion size and aortic CD11b(+)CD11c(+) myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

  17. Comprehensive Exploration of Novel Chimeric Transcripts in Clear Cell Renal Cell Carcinomas Using Whole Transcriptome Analysis

    PubMed Central

    Gotoh, Masahiro; Ichikawa, Hitoshi; Arai, Eri; Chiku, Suenori; Sakamoto, Hiromi; Fujimoto, Hiroyuki; Hiramoto, Masaki; Nammo, Takao; Yasuda, Kazuki; Yoshida, Teruhiko; Kanai, Yae

    2014-01-01

    The aim of this study was to clarify the participation of expression of chimeric transcripts in renal carcinogenesis. Whole transcriptome analysis (RNA sequencing) and exploration of candidate chimeric transcripts using the deFuse program were performed on 68 specimens of cancerous tissue (T) and 11 specimens of non-cancerous renal cortex tissue (N) obtained from 68 patients with clear cell renal cell carcinomas (RCCs) in an initial cohort. As positive controls, two RCCs associated with Xp11.2 translocation were analyzed. After verification by reverse transcription (RT)-PCR and Sanger sequencing, 26 novel chimeric transcripts were identified in 17 (25%) of the 68 clear cell RCCs. Genomic breakpoints were determined in five of the chimeric transcripts. Quantitative RT-PCR analysis revealed that the mRNA expression levels for the MMACHC, PTER, EPC2, ATXN7, FHIT, KIFAP3, CPEB1, MINPP1, TEX264, FAM107A, UPF3A, CDC16, MCCC1, CPSF3, and ASAP2 genes, being partner genes involved in the chimeric transcripts in the initial cohort, were significantly reduced in 26 T samples relative to the corresponding 26 N samples in the second cohort. Moreover, the mRNA expression levels for the above partner genes in T samples were significantly correlated with tumor aggressiveness and poorer patient outcome, indicating that reduced expression of these genes may participate in malignant progression of RCCs. As is the case when their levels of expression are reduced, these partner genes also may not fully function when involved in chimeric transcripts. These data suggest that generation of chimeric transcripts may participate in renal carcinogenesis by inducing dysfunction of tumor-related genes. PMID:25230976

  18. Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects.

    PubMed

    Kuroda, Naoto; Karashima, Takashi; Inoue, Keiji; Kasajima, Atsuko; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Petersson, Fredirk; Lopez, Jose I; Cohen, Ronald J; Michal, Michal; Hes, Ondrej

    2015-03-01

    Rhabdoid morphology in renal cell carcinoma (RCC) may, like sarcomatoid change, be perceived as a type of dedifferentiation, and is a poor prognostic factor. Histologically, rhabdoid neoplastic cells are round to polygonal cells with globular eosinophilic cytoplasmic inclusions and eccentric vesicular nuclei and enlarged nucleoli. All types of RCC, including clear cell, papillary, chromophobe, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC, may display a variably prominent rhabdoid phenotype. Immunohistochemically, the cytoplasm of rhabdoid cells shows positivity for vimentin and/or cytokeratin. Ultrastructurally, cytoplasmic whorls/aggregates of intermediate filaments correspond to light microscopically observed inclusions. Genetically, a previous report suggests that combined loss of BAP1 and PBRM1 may be associated with rhabdoid morphology. As with sarcomatoid change, pathologists should describe, estimate and state the proportion of tumor cells with a rhabdoid phenotype in the routine pathology report of RCC. PMID:26017874

  19. Renal-type clear cell carcinoma of the prostate: a diagnostic challenge.

    PubMed

    Patne, Shashikant C U; Johri, Nidhi; Katiyar, Richa; Trivedi, Sameer; Dwivedi, Uday Shankar

    2015-01-01

    A 72-year-old male presented with urinary symptoms. His serum prostate specific antigen level was 65.2 ng/ml. His radical prostatectomy specimen showed clear cell lesion reminiscent of the clear cell renal cell carcinoma along with acinar type of prostatic adenocarcinoma, Gleason score 4 + 4. The lesional clear cells were positive for pancytokeratin, epithelial membrane antigen, CD10, vimentin, and AMACR while negative for 34βE12, CK7, prostate specific antigen, and PAX8. The final diagnosis was renal-type clear cell carcinoma of the prostate. A follow-up of 20 months did not show metastasis. We herein report fifth case of renal-type clear cell carcinoma of the prostate. PMID:26498435

  20. Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering

    PubMed Central

    Batchelder, Cynthia A.; Martinez, Michele L.; Tarantal, Alice F.

    2015-01-01

    Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise

  1. Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience

    PubMed Central

    Strati, Paolo; Nasr, Samih H.; Leung, Nelson; Hanson, Curtis A.; Chaffee, Kari G.; Schwager, Susan M.; Achenbach, Sara J.; Call, Timothy G.; Parikh, Sameer A.; Ding, Wei; Kay, Neil E.; Shanafelt, Tait D.

    2015-01-01

    While the renal complications of plasma cell dyscrasia have been well-described, most information in patients with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis is derived from case reports. This is a retrospective analysis of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who underwent kidney biopsy for renal insufficiency and/or nephrotic syndrome. Between January 1995 and June 2014, 49 of 4,024 (1.2%) patients with chronic lymphocytic leukemia (n=44) or monoclonal B-cell lymphocytosis (n=5) had a renal biopsy: 34 (69%) for renal insufficiency and 15 (31%) for nephrotic syndrome. The most common findings on biopsy were: membranoproliferative glomerulonephritis (n=10, 20%), chronic lymphocytic leukemia interstitial infiltration as primary etiology (n=6, 12%), thrombotic microangiopathy (n=6, 12%), and minimal change disease (n=5, 10%). All five membranoproliferative glomerulonephritis patients treated with rituximab, cyclophosphamide and prednisone-based regimens had recovery of renal function compared to 0/3 patients treated with rituximab with or without steroids. Chronic lymphocytic leukemia infiltration as the primary cause of renal abnormalities was typically observed in relapsed/refractory patients (4/6). Thrombotic microangiopathy primarily occurred as a treatment-related toxicity of pentostatin (4/6 cases), and resolved with drug discontinuation. All cases of minimal change disease resolved with immunosuppressive agents only. Renal biopsy plays an important role in the management of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who develop renal failure and/or nephrotic syndrome. PMID:26088927

  2. Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience.

    PubMed

    Strati, Paolo; Nasr, Samih H; Leung, Nelson; Hanson, Curtis A; Chaffee, Kari G; Schwager, Susan M; Achenbach, Sara J; Call, Timothy G; Parikh, Sameer A; Ding, Wei; Kay, Neil E; Shanafelt, Tait D

    2015-09-01

    While the renal complications of plasma cell dyscrasia have been well-described, most information in patients with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis is derived from case reports. This is a retrospective analysis of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who underwent kidney biopsy for renal insufficiency and/or nephrotic syndrome. Between January 1995 and June 2014, 49 of 4,024 (1.2%) patients with chronic lymphocytic leukemia (n=44) or monoclonal B-cell lymphocytosis (n=5) had a renal biopsy: 34 (69%) for renal insufficiency and 15 (31%) for nephrotic syndrome. The most common findings on biopsy were: membranoproliferative glomerulonephritis (n=10, 20%), chronic lymphocytic leukemia interstitial infiltration as primary etiology (n=6, 12%), thrombotic microangiopathy (n=6, 12%), and minimal change disease (n=5, 10%). All five membranoproliferative glomerulonephritis patients treated with rituximab, cyclophosphamide and prednisone-based regimens had recovery of renal function compared to 0/3 patients treated with rituximab with or without steroids. Chronic lymphocytic leukemia infiltration as the primary cause of renal abnormalities was typically observed in relapsed/refractory patients (4/6). Thrombotic microangiopathy primarily occurred as a treatment-related toxicity of pentostatin (4/6 cases), and resolved with drug discontinuation. All cases of minimal change disease resolved with immunosuppressive agents only. Renal biopsy plays an important role in the management of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who develop renal failure and/or nephrotic syndrome. PMID:26088927

  3. Sporadic renal hemangioblastoma with CA9, PAX2 and PAX8 expression: diagnostic pitfall in the differential diagnosis from clear cell renal cell carcinoma

    PubMed Central

    Kuroda, Naoto; Agatsuma, Yoshiko; Tamura, Masato; Martinek, Petr; Hes, Ondrej; Michal, Michal

    2015-01-01

    To date, 13 cases of sporadic renal hemangioblastoma have been reported. In this article, we report such a case that might cause the diagnostic pitfall. A 37-year-old Japanese was found to have a renal mass by periodic medical check-up. He underwent radical nephrectomy. Macroscopically, the tumor was well-defined without fibrous capsule and the cut surface of the tumor exhibited light brown to gray-tan color without hemorrhage or necrosis. Microscopically, the tumor was made up of large polygonal to short spindle cells with eosinophilic cytoplasm with occasional vacuolization and abundant arborizing capillary network. Immunohistochemically, neoplastic cells showed diffuse positivity for inhibin-alpha, S-100 protein, vimentin, CA9, PAX2 and PAX8, but negativity for cytokeratin CAM5.2, alpha smooth muscle actin, Melanosome, Melan A, TFE3 and cathepsin K. In genetic analyses, this tumor showed no changes of VHL gene mutation, hypermethylation and loss of heterozygosity of chromosome 3p. Additionally, G-band karyotype and array comparative genomic hybridization studies showed a normal chromosome. In conclusion, the positivity for CA9, PAX2 and PAX8 in sporadic renal hemangioblastoma may cause the critical diagnostic pitfall in the differential diagnosis from clear cell renal cell carcinoma. Pathologists need to pay attention to systemic evaluation including macroscopic, microscopic and immunohistochemical findings. In some cases, molecular genetic study may be necessary. PMID:25973115

  4. [Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma].

    PubMed

    Fedhila Ben Ayed, F; Rhayem, S; Doghri, R; Ben Hassine, L; Khemiri, M; Mrad, K; Bellagha, I; Barsaoui, S

    2016-02-01

    Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents. PMID:26702489

  5. In situ non-ischemic enucleation of multilocular cystic renal cell carcinoma using a microwave coagulator.

    PubMed

    Kagebayashi, Y; Hirao, Y; Samma, S; Fukui, Y; Hirohashi, R

    1995-11-01

    A case of multilocular cystic renal cell carcinoma is reported, in which nephron-sparing surgery was done using microwave tissue coagulation. A 37-year-old man was referred to our outpatient clinic for a multilocular cystic tumor, 4.5 cm in diameter, in the middle-lower portion of the right kidney, which was detected by ultrasound during a health checkup. The patient had been found to have the same cystic mass on a CT done during another health checkup 1.5 years before. The tumor showed no growth during the 1.5-year period. With a diagnosis of multilocular cystic renal cell carcinoma, T2N0M0, in situ non-ischemic tumor enucleation was done using a microwave tissue coagulator (Microtaze, Heiwa Electronics Industry Inc., Tokyo). Operation time was 150 minutes and blood loss was 135 cc. The histological diagnosis was renal cell carcinoma, T2N0M0V0, cystic type, clear cell subtype, grade 1. Diagnostic imaging done postoperatively showed no sign of damage to renal function. In this report, the characteristics of multilocular cystic renal carcinoma are reviewed from the literature, and the advantages of nephron-sparing surgery for this type of renal tumor are discussed. In addition, an operative technique of tumor enucleation used in this case and the characteristics of Microtaze are introduced. PMID:8749956

  6. Acute renal failure and type B lactic acidosis as first manifestation of extranodal T-cell lymphoblastic lymphoma

    PubMed Central

    Yun, Seongseok; Walker, Courtney N; Vincelette, Nicole D; Anwer, Faiz

    2014-01-01

    We describe a rare case of a 19-year-old male patient with a history of epilepsy and developmental delay who presented with acute renal failure (ARF) and lactic acidosis (LA) as the first manifestation of T-cell lymphoblastic lymphoma. Renal ultrasound and CT of the abdomen showed renal parenchymal infiltration, and renal biopsy demonstrated T-cell lymphoblastic lymphoma. LA, ARF and electrolyte abnormalities were refractory to the initial treatment of bicarbonate infusion and hydration. However, these abnormalities rapidly normalised after the initiation of chemotherapy, suggesting that the LA and ARF were secondary to lymphomatous renal infiltration. PMID:24913086

  7. VEGFR-1 Expression Relates to Fuhrman Nuclear Grade of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Lkhagvadorj, Sayamaa; Oh, Sung Soo; Lee, Mi-Ra; Jung, Jae Hung; Chung, Hyun Chul; Cha, Seung-Kuy; Eom, Minseob

    2014-01-01

    Background: Increasing evidence suggests that vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 signaling may play an important role in the progression of pathological angiogenesis that occurs in many tumors, including renal cell carcinoma (RCC). Therapeutic targeting directed against VEGF and VEGFR-2 has been proven to be successful for metastatic clear cell RCC (CCRCC). However, the expression of VEGFR-1 and its association with prognostic parameters of CCRCC in the tumorigenesis of renal cancer remains unclear. Therefore, we examined the expression of VEGFR-1 and its prognostic significance in CCRCC. Methods: Immunohistochemical staining for VEGFR-1 was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Six of these cases were available for Western blot analyses. The results were compared with various clinicopathologic parameters of CCRCC and patients’ survival. Results: VEGFR-1 expression was detected in 59 cases (46.8%) of CCRCC. Higher VEGFR-1 expression was significantly correlated with a lower Fuhrman nuclear grade and the absence of renal pelvis invasion, although it was not related to patients’ survival. Western blot analyses showed higher VEGFR-1 expression in low grade tumors. Conclusion: VEGFR-1 expression may be associated with favorable prognostic factors, particularly a lower Fuhrman nuclear grade in CCRCC. PMID:26064856

  8. (1) H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    PubMed

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors. PMID:26620126

  9. Selected tumor markers in the routine diagnosis of chromophobe renal cell carcinoma.

    PubMed

    Badowska-Kozakiewicz, Anna M; Budzik, Michał P; Koczkodaj, Paweł; Przybylski, Jacek

    2016-08-01

    Renal cell carcinoma is one of the most malignant tumors, affecting men more frequently than women and constituting nearly 90% of all kidney tumors. Chromophobe renal cell carcinoma has been described as a new histological type of renal cell carcinoma. Chromophobe renal cell carcinoma constitutes up to 5% of all cases of kidney cancer. It is characterized by a significant number of deletions in many chromosomes, as well as the loss of entire chromosomes. Chromophobe renal cell carcinoma arises from tubular cells or cells of the macula densa. In contrast to other types of kidney cancer, it occurs with equal frequency in men and women, mostly in the sixth decade of life. It is characterized by a relatively good prognosis and exhibits a low degree of malignancy. Histopathologic diagnosis of ChRCC can be a diagnostic challenge because these tumors may resemble oncocytoma or conventional cancer. Research by Mathers et al. proposed the use of cytokeratin 7 as a marker useful in the differentiation of these changes. PMID:27478468

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

    PubMed

    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

  11. Epigenomics of clear cell renal cell carcinoma: mechanisms and potential use in molecular pathology

    PubMed Central

    Xing, Tianying

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic malignancy with numerous genetic and epigenetic alterations. This review summarizes the recent major findings of epigenetic alterations including DNA methylation, histone modifications, microRNAs and recently identified long noncoding RNAs in the development and progression of ccRCC. These epigenetic profilings can provide a promising means of prognostication and early diagnosis for patients with ccRCCs. With the developed high-throughput technologies nowadays, the epigenetic analyses will have possible clinical applications in the molecular pathology of ccRCC. PMID:27041930

  12. High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman.

    PubMed

    Venniyoor, Ajit; Essam, Abdul Monem; Ramadhan, Fatma; Keswani, Heeranand; Mehdi, Itrat; Bahrani, Bassim Al

    2016-01-01

    It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed. PMID:27356693

  13. Robotic radical nephrectomy for renal cell carcinoma: a systematic review

    PubMed Central

    2014-01-01

    Background Laparoscopic radical nephrectomy (LRN) is the actual gold-standard for the treatment of clinically localized renal cell carcinoma (RCC) (cT1-2 with no indications for nephron-sparing surgery). Limited evidence is currently available on the role of robotics in the field of radical nephrectomy. The aim of the current study was to provide a systematic review of the current evidence on the role of robotic radical nephrectomy (RRN) and to analyze the comparative studies between RRN and open nephrectomy (ON)/LRN. Methods A Medline search was performed between 2000–2013 with the terms “robotic radical nephrectomy”, “robot-assisted laparoscopic nephrectomy”, “radical nephrectomy”. Six RRN case-series and four comparative studies between RRN and (ON)/pure or hand-assisted LRN were identified. Results Current literature produces a low level of evidence for RRN in the treatment of RCC, with only one prospective study available. Mean operative time (OT) ranges between 127.8-345 min, mean estimated blood loss (EBL) ranges between 100–273.6 ml, and mean hospital stay (HS) ranges between 1.2-4.3 days. The comparison between RRN and LRN showed no differences in the evaluated outcomes except for a longer OT for RRN as evidenced in two studies. Significantly higher direct costs and costs of the disposable instruments were also observed for RRN. The comparison between RRN and ON showed that ON is characterized by shorter OT but higher EBL, higher need of postoperative analgesics and longer HS. Conclusions No advantage of robotics over standard laparoscopy for the treatment of clinically localized RCC was evidenced. Promising preliminary results on oncologic efficacy of RRN have been published on the T3a-b disease. Fields of wider application of robotics should be researched where indications for open surgery still persist. PMID:25234265

  14. Cabozantinib versus everolimus in advanced renal cell carcinoma

    PubMed Central

    Choueiri, Toni K.; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul; Rini, Brian I.; Donskov, Frede; Hammers, Hans; Hutson, Thomas E.; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J.; Bjarnason, Georg A.; Géczi, Lajos; Keam, Bhumsuk; Moroto, Pablo; Heng, Daniel Y. C.; Schmidinger, Manuela; Kantoff, Philip W.; Borgman, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M.; Tannir, Nizar M.; Motzer, Robert J.

    2016-01-01

    Background Cabozantinib is an oral small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL; each has been implicated in metastatic renal cell carcinoma (RCC) pathobiology or development of resistance to antiangiogenic drugs. This randomized open-label phase 3 trial evaluated the efficacy of cabozantinib compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. Methods The trial randomized 658 patients to receive cabozantinib at a dose of 60 mg daily, or everolimus at a dose of 10 mg daily. The primary endpoint was progression-free survival. Secondary efficacy endpoints were overall survival and objective response rate. Results Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The risk of progression or death was 42% lower with cabozantinib compared to everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P < 0.001). Objective response rates were 21% with cabozantinib and 5% with everolimus (P < 0.001). A planned interim analysis showed that overall survival was improved with cabozantinib (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary. Adverse events (grade 3 or 4, regardless of causality) were reported in 74% of cabozantinib patients and 65% of everolimus patients. Discontinuation of study treatment for adverse events occurred in 9.1% of cabozantinib patients and 10% of everolimus patients. Conclusions Cabozantinib improved progression-free survival compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. PMID:26406150

  15. Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

    PubMed

    Alfaro, Clint M; Jarmusch, Alan K; Pirro, Valentina; Kerian, Kevin S; Masterson, Timothy A; Cheng, Liang; Cooks, R Graham

    2016-08-01

    Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for

  16. Lymphangitic retroperitoneal carcinomatosis occurring from metastatic sarcomatoid chromophobe renal cell carcinoma.

    PubMed

    Alimchandani, Meghna; Lara, Karlena; Tsokos, Maria; Linehan, W M; Merino, Maria J

    2014-03-01

    Forty -five year-old man with left renal mass underwent nephrectomy to reveal 20cm tumor diagnosed as sarcomatoid chromophobe renal cell carcinoma (CRCC). Lymph node metastasis of chromophobe and sarcomatoid components, disseminated tumor in retroperitoneal fat, lymphatic vessels, peri-renal adipose tissue in lymphangitic carcinomatosis pattern were identified. Chromophobe epithelial cells EMA, c-Kit, cytokeratin 7 positive; sarcomatoid cells were CD10, SMA positive with high proliferation index . Chromophobe epithelial cells had loss of heterozygosity (LOH) in chromosomes 1p, 1q while sarcomatoid cells had LOH in 3p,1p, 1q. In conclusion, sarcomatoid CRCC has aggressive biologic behavior and potential to metastasize in unusual patterns. PMID:24696789

  17. Case-control study of renal cell carcinoma in relation to occupation, smoking, and alcohol consumption

    SciTech Connect

    Brownson, R.C.

    1988-05-01

    A case-control study based on data from a cancer registry was conducted to evaluate the effects of smoking, alcohol use, and occupation on renal cell cancer risk. Information was obtained for 326 male and female cases and 978 age- and sex-matched controls. Elevated risks were identified for cigarette smokers and for men employed as truck drivers. No relationship between alcohol consumption and renal cancer was observed.

  18. VHL-dependent alterations in the secretome of renal cell carcinoma: Association with immune cell response?

    PubMed

    Stehle, Franziska; Leisz, Sandra; Schulz, Kristin; Schwurack, Nicolle; Weber, Nico; Massa, Chiara; Kalich, Jana; Fahldieck, Corinna; Seliger, Barbara

    2015-12-22

    Secreted proteins could modulate the interaction between tumor, stroma and immune cells within the tumor microenvironment thereby mounting an immunosuppressive tumor microenvironment. In order to determine the secretome-mediated, von Hippel Lindau (VHL)-regulated cross-talk between tumor cells and T lymphocytes peripheral blood mononuclear cells (PBMC) from healthy donors were either cultured in conditioned media obtained from normoxic and hypoxic human VHL-deficient renal cell carcinoma (RCC) cell line (786-0VHL-) and its wild type (wt) VHL-transfected counterpart (786-0VHL+) or directly co-cultured with both cell lines. An increased T cell proliferation was detected in the presence of 786-0VHL+-conditioned medium. By applying a quantitative proteomic-based approach using differential gel electrophoresis followed by mass spectrometry fourteen proteins were identified to be differentially expressed within the secretome of 786-0VHL- cells when compared to that of 786-0VHL+ cells. All proteins identified were involved in multiple tumor-associated biological functions including immune responses. Functional studies on manganese superoxide dismutase 2 (MnSOD2) demonstrated that it was a regulator of T cell activation-induced oxidative signaling and cell death. Direct effects of soluble MnSOD2 on the growth properties and interleukin 2 (IL-2) secretion of T cells could be demonstrated underlining the critical role of extracellular MnSOD2 levels for T cell proliferation and activation. PMID:26486078

  19. VHL-dependent alterations in the secretome of renal cell carcinoma: Association with immune cell response?

    PubMed Central

    Stehle, Franziska; Leisz, Sandra; Schulz, Kristin; Schwurack, Nicolle; Weber, Nico; Massa, Chiara; Kalich, Jana; Fahldieck, Corinna; Seliger, Barbara

    2015-01-01

    Secreted proteins could modulate the interaction between tumor, stroma and immune cells within the tumor microenvironment thereby mounting an immunosuppressive tumor microenvironment. In order to determine the secretome-mediated, von Hippel Lindau (VHL)-regulated cross-talk between tumor cells and T lymphocytes peripheral blood mononuclear cells (PBMC) from healthy donors were either cultured in conditioned media obtained from normoxic and hypoxic human VHL-deficient renal cell carcinoma (RCC) cell line (786-0VHL−) and its wild type (wt) VHL-transfected counterpart (786-0VHL+) or directly co-cultured with both cell lines. An increased T cell proliferation was detected in the presence of 786-0VHL+-conditioned medium. By applying a quantitative proteomic-based approach using differential gel electrophoresis followed by mass spectrometry fourteen proteins were identified to be differentially expressed within the secretome of 786-0VHL− cells when compared to that of 786-0VHL+ cells. All proteins identified were involved in multiple tumor-associated biological functions including immune responses. Functional studies on manganese superoxide dismutase 2 (MnSOD2) demonstrated that it was a regulator of T cell activation-induced oxidative signaling and cell death. Direct effects of soluble MnSOD2 on the growth properties and interleukin 2 (IL-2) secretion of T cells could be demonstrated underlining the critical role of extracellular MnSOD2 levels for T cell proliferation and activation. PMID:26486078

  20. Flagellar cells and ciliary cells in the renal tubule of elasmobranchs.

    PubMed

    Lacy, E R; Luciano, L; Reale, E

    1989-01-01

    Flagella or cilia are present on most epithelial cells in the renal tubule of elasmobranch fishes (little skate, spiny dogfish, smooth dogfish, Atlantic sharpnose, scalloped hammerhead, cow-nosed ray). Flagellar cells, those with numerous flagella ordered in one, two, or more rows on the luminal surface, are shown here for the first time in a vertebrate. The flagellar cells are intercalated among other epithelial cells, each bearing a single cilium, from Bowman's capsule to the third subdivision of the intermediate segment of the nephron. The flagella form undulated ribbons up to 55 microns long. In every ribbon the axis of the central pair of microtubules in the axoneme is oriented parallel to the long axis of the flagellar row. This suggests a beat perpendicular to these two axes. The arrangement of the flagella in ribbons most likely promotes movement of glomerular filtrate down the renal tubule. Cells bearing numerous cilia occur in the large collecting ducts of spiny dogfish but without apparent preferential orientation of the cilia. PMID:2575649

  1. [A Case of Small Intestinal Metastases from Renal Cell Carcinoma with Massive Bleeding].

    PubMed

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Ohira, Masaichi; Ohsawa, Masahiko; Hirakawa, Kosei

    2015-11-01

    A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors. PMID:26805327

  2. Missense Mutations in Fumarate Hydratase in Multiple Cutaneous and Uterine Leiomyomatosis and Renal Cell Cancer

    PubMed Central

    Alam, N. Afrina; Olpin, Simon; Rowan, Andrew; Kelsell, David; Leigh, Irene M.; Tomlinson, Ian P. M.; Weaver, Todd

    2005-01-01

    Heterozygous germline mutations in fumarate hydratase (FH) predispose to the multiple cutaneous and uterine leiomyomatosis syndrome (MCUL), which, when co-existing with renal cancer, is also known as hereditary leiomyomatosis and renal cell cancer. Twenty-seven distinct missense mutations represent 68% of FH mutations reported in MCUL. Here we show that FH missense mutations significantly occurred in fully conserved residues and in residues functioning in the FH A-site, B-site, or subunit-interacting region. Of 24 distinct missense mutations, 13 (54%) occurred in the substrate-binding A-site, 4 (17%) in the substrate-binding B-site, and 7 (29%) in the subunit-interacting region. Clustering of missense mutations suggested the presence of possible mutational hotspots. FH functional assay of lymphoblastoid cell lines from 23 individuals with heterozygous FH missense mutations showed that A-site mutants had significantly less residual activity than B-site mutants, supporting data from Escherichia coli that the A-site is the main catalytic site. Missense FH mutations predisposing to renal cancer had no unusual features, and identical mutations were found in families without renal cancer, suggesting a role for genetic or environmental factors in renal cancer development in MCUL. That all missense FH mutations associating with MCUL/hereditary leiomyomatosis and renal cell cancer showed diminished FH enzymatic activity suggests that the tumor suppressor role of fumarate hydratase may relate to its enzymatic function. PMID:16237213

  3. Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts.

    PubMed Central

    Moe, O W; Miller, R T; Horie, S; Cano, A; Preisig, P A; Alpern, R J

    1991-01-01

    Increased Na/H antiporter activity has been demonstrated after in vivo chronic metabolic acidosis as well as in vitro acid preincubation of cultured rabbit renal tubule cells. To study the underlying molecular mechanisms of this adaptive increase in Na/H antiporter activity, the present studies examined the effect of low pH media on Na/H antiporter activity and mRNA abundance in cultured renal tubule cells. Na/H antiporter activity was increased by 60% in a mouse renal cortical tubule cell line (MCT), and by 90% in an opossum kidney cell line (OKP) after 24 h of preincubation in acid (low [HCO3]) media. The ethylisopropylamiloride sensitivity of the Na/H antiporters were different in these two cell lines (MCT IC50 = 65 nM; OKP IC50 = 4.5 microM). In MCT cells, Na/H antiporter mRNA abundance measured by RNA blots increased by two- to fivefold after 24 h in low [HCO3] media. Na/H antiporter mRNA abundance was also increased in MCT cells with high CO2 preincubation as well as in rat renal cortex with in vivo chronic acid feeding. In contrast to renal epithelia, acid preincubation of NIH 3T3 fibroblasts led to suppression of Na/H antiporter activity. RNA blots of 3T3 fibroblasts revealed the same size Na/H antiporter transcript as in MCT cells. However, Na/H antiporter mRNA levels were suppressed by acid preincubation. These studies demonstrate differential regulation of Na/H antiporter activity and mRNA abundance in renal epithelial cells and fibroblasts in response to an acidotic environment. Images PMID:1658050

  4. Mesenchymal Stem Cells (MSC) Prevented the Progression of Renovascular Hypertension, Improved Renal Function and Architecture

    PubMed Central

    Oliveira-Sales, Elizabeth B.; Maquigussa, Edgar; Semedo, Patricia; Pereira, Luciana G.; Ferreira, Vanessa M.; Câmara, Niels O.; Bergamaschi, Cassia T.; Campos, Ruy R.; Boim, Mirian A.

    2013-01-01

    Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×105 cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future. PMID:24223811

  5. Epigenetic alterations of Krüppel-like factor 4 and its tumor suppressor function in renal cell carcinoma.

    PubMed

    Li, Heng; Wang, Ji; Xiao, Wei; Xia, Ding; Lang, Bin; Yu, Gan; Guo, Xiaolin; Guan, Wei; Wang, Zhihua; Hu, Zhiquan; Liu, Jihong; Ye, Zhangqun; Xu, Hua

    2013-10-01

    Krüppel-like factor 4 (KLF4) is a transcription factor that can have divergent functions in different malignancies. The expression and role of KLF4 in renal cell cancer remain unclear. The purpose of this study is to determine epigenetic alterations and possible roles of KLF4 in renal cell carcinoma. The KLF4 expression in primary renal cell cancer tissues and case-matched normal renal tissues was determined by protein and messenger RNA analyses. The epigenetic alterations were detected by methylation-specific PCR and Sequenom MassARRAY. Kaplan-Meier curves and the log-rank test were used for the survival analysis. The effects of KLF4 on cell growth and epithelial-to-mesenchymal transition (EMT) were determined in renal cancer cell lines after viral-based and RNA activation-mediated overexpression of KLF4. In vivo antitumor activity of KLF4 was evaluated by using stably KLF4-transfected renal cancer cells. KLF4 expression was dramatically decreased in various pathological types of renal cancer and associated with poor survival after nephrectomy. Hypermethylation of KLF4 promoter mainly contributed to its expression suppression. In vitro assays indicated that KLF4 overexpression inhibited renal cancer cell growth and survival. KLF4 overexpression also suppressed renal cancer cell migration and invasion by altering the EMT-related factors. In vivo assay showed that ectopic expression of KLF4 also inhibited tumorigenicity and metastasis of renal cancer. Our results suggest that KLF4 is a putative tumor suppressor gene epigenetically silenced in renal cell cancers by promoter CpG methylation and that it has prognostic value for renal cell progression. PMID:23722653

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

    PubMed

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

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

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

    PubMed Central

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

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

  8. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    PubMed

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p < 0.01) and 1000 ng/mL (p < 0.05) were used. In conclusion, auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration. PMID:25707523

  9. An association between antibodies specific for endothelial cells and renal transplant failure.

    PubMed

    Perrey, C; Brenchley, P E; Johnson, R W; Martin, S

    1998-06-01

    Human leucocyte antigen (HLA)-specific antibodies, present at the time of transplant, cause renal transplant rejection but cases of rejection of HLA-identical renal transplants indicate that antibodies to non-HLA antigens may also be detrimental. There is increasing evidence that antibodies to antigens present on endothelial cells and monocytes, and on endothelial cells alone, are associated with transplant rejection. We investigated 105 patients with failed renal transplants for the presence of endothelial cell reactive antibodies and compared them with 94 successful transplant patients to determine the role of non-HLA antibodies in transplant failure. Patient sera were tested by enzyme-linked immunoabsorbent assay (ELISA) using as a target fixed cells either from the endothelial/epithelial cell line EAHy.926 or primary cultures of human umbilical vein endothelial cells. Antibody binding was detected using an alkaline phosphatase-conjugated anti-human immunoglobulin G (IgG) antibody. Fourteen of the 105 failed transplant patients had endothelial cell-reactive antibodies as compared with only three of the 94 patients with successful transplants (Fisher's exact test, p = 0.02). Antibody-positive sera were absorbed with the epithelial cell line A549 to remove antibodies directed against the epithelial component of EAHy.926 and with a pool of lymphoblastoid cell line cells to remove HLA-specific antibodies. Absorption did not reduce antibody activity showing the antibodies to be directed against endothelial cell determinants. Antibody-positive sera were also tested by flow cytometry against the monocyte cell line THP-1 and 13 of the 14 patients were negative. In conclusion, we have demonstrated the presence of IgG antibodies directed against endothelial cell determinants in renal transplant recipients in association with renal transplant failure. PMID:9777698

  10. Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma.

    PubMed

    Blanco, Lorena; Larrinaga, Gorka; Pérez, Itxaro; López, José I; Gil, Javier; Agirregoitia, Ekaitz; Varona, Adolfo

    2008-04-01

    Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors. PMID:18216146

  11. Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines

    PubMed Central

    CHEN, XIAO-MENG; ZHANG, MENG; FAN, PENG-LI; QIN, YU-HUA; ZHAO, HONG-WEI

    2016-01-01

    Previous studies have demonstrated that the benzo[c]phenanthridine alkaloid chelerythrine chloride (CC) has inhibitory effects on various tumors. However, the anticancer activity of CC and its underlying mechanisms have not been elucidated in renal cancer cells. The present study examined the effects of CC on growth inhibition and apoptosis of renal cancer cells in vitro and in vivo. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed that CC markedly suppressed the growth of HEK-293 and human renal cancer SW-839 cells in a time- and dose-dependent manner. The xenograft mouse model, which was performed in nude mice, exhibited a reduced tumor growth following CC treatment. In addition, the present study revealed that CC significantly decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, which was accompanied by upregulation of p53, B-cell lymphoma 2 (Bcl-2)-associated X protein, cleaved caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP), and downregulation of Bcl-2, caspase-3 and PARP. Furthermore, the use of PD98059, a specific mitogen-activated protein kinase kinase inhibitor, potentiated the proapoptotic effects of CC, which indicated that CC may induce apoptosis in renal cancer cells partly via inhibition of ERK activity. Overall, the results of the present study demonstrated that CC may be developed as a potential anticancer treatment for patients with renal cancer. PMID:27313717

  12. Renal-type Clear Cell Carcinoma Occurring in the Prostate With Zinner Syndrome

    PubMed Central

    Sato, Yuichi; Kataoka, Masao; Hata, Junya; Akaihata, Hidenori; Ogawa, Soichiro; Kojima, Yoshiyuki

    2016-01-01

    We report a case of clear cell carcinoma occurring in the prostate with Zinner syndrome in a 64-year-old man. Based on the immunohistochemical findings, it was concluded that this tumor represented primary renal-type clear cell carcinoma arising in the prostate. After receiving radical cystoprostatectomy, he was treated with tyrosine kinase inhibitor (TKI) therapy for local recurrence in accordance with the protocol of renal cell carcinoma (RCC) treatment, because microarray cluster analysis using a resected sample demonstrated that the present case belonged to the cluster group of RCC. PMID:26793589

  13. Renal-type Clear Cell Carcinoma Occurring in the Prostate With Zinner Syndrome.

    PubMed

    Sato, Yuichi; Kataoka, Masao; Hata, Junya; Akaihata, Hidenori; Ogawa, Soichiro; Kojima, Yoshiyuki

    2016-03-01

    We report a case of clear cell carcinoma occurring in the prostate with Zinner syndrome in a 64-year-old man. Based on the immunohistochemical findings, it was concluded that this tumor represented primary renal-type clear cell carcinoma arising in the prostate. After receiving radical cystoprostatectomy, he was treated with tyrosine kinase inhibitor (TKI) therapy for local recurrence in accordance with the protocol of renal cell carcinoma (RCC) treatment, because microarray cluster analysis using a resected sample demonstrated that the present case belonged to the cluster group of RCC. PMID:26793589

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

    PubMed

    Hussain, Faiz; Yedavalli, Nina; Loeffler, David; Kajdacsy-Balla, Andre

    2016-01-01

    Renal cell carcinoma is a common cancer, known for its aggressive behavior and ability to metastasize nearly every organ system in the body. While the cancer commonly spreads to a select few organs and metastasis usually develops within 5 years of diagnosis, there have been numerous case reports of atypical sites of metastasis and cases of relapse up to decades after treatment. We present a case a 65-year-old male who presented with right preauricular swelling 8 years after the initial diagnosis and right nephrectomy for clear cell renal cell cancer. We take a look at previous case reports with similar presentations. PMID:27609721

  15. Localized Pleural Metastases of Renal Cell Carcinoma After Nephrectomy: A Case Report and Literature Review.

    PubMed

    Yasuda, Yuichiro; Tobino, Kazunori; Ko, Yuki; Asaji, Mina; Yamaji, Yoshikazu; Tsuruno, Kosuke; Mukasa, Yosuke; Ebi, Noriyuki

    2016-01-01

    We herein report the case of a 61-year-old Japanese male with localized pleural metastases of renal cell carcinoma. The patient was admitted to our hospital because of dyspnea on exertion and left-sided pleural effusion. He had undergone right radical nephrectomy 10 years previously. Contrast-enhanced whole-body computed tomography revealed scattered nodular thickening of the left pleura with contrast enhancement and left-sided pleural effusion. Thoracoscopy performed under local anesthesia was applied to obtain a biopsy of the pleural nodules, and the specimen was consequently diagnosed as exhibiting pleural metastasis of renal cell carcinoma, clear cell type. PMID:26705014

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

    SciTech Connect

    Morizane, Ryuji; Monkawa, Toshiaki; Itoh, Hiroshi

    2009-12-25

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

  17. Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome

    PubMed Central

    Kim, Ji-Hee; Hwang, Kyu-Hee; Lkhagvadorj, Sayamaa; Jung, Jae Hung; Chung, Hyun Chul; Park, Kyu-Sang; Kong, In Deok

    2016-01-01

    Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC. PMID:27162484

  18. Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.

    PubMed

    Kim, Ji-Hee; Hwang, Kyu-Hee; Lkhagvadorj, Sayamaa; Jung, Jae Hung; Chung, Hyun Chul; Park, Kyu-Sang; Kong, In Deok; Eom, Minseob; Cha, Seung-Kuy

    2016-05-01

    Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC. PMID:27162484

  19. Expression of insulin-like growth factor family genes in clear cell renal cell carcinoma

    PubMed Central

    Białożyt, Michał; Plato, Marta; Mazurek, Urszula; Braczkowska, Bogumiła

    2016-01-01

    Aim of the study Despite significant progress in the pathology of clear cell renal cell carcinoma (ccRCC), diagnostic and predictive factors of major importance have not been discovered. Some hopes are associated with insulin-like growth factors. The aim of the study was to compare the expression of genes for insulin-like growth factor family in tumours and in tissue of kidneys without cancer. Material and methods Fifty-two patients years with clear cell renal cell cancer were qualified to the study group; patients nephrectomised because of hydronephrosis were included in the control group. Expression of genes were evaluated by RT-PCR. Results Expression of IGFR-1 gene in tumour accounts for about 60% of cases. The incidence is higher than in corresponding adjacent non-cancerous kidney tissues and higher (but with no statistical significance) than in kidney without cancer. Expression of IGFR-2 gene in tumours has not been established. The incidence of the expression in corresponding adjacent non-cancerous kidney tissues is small. Expression of this gene has been present in all specimens from kidneys without cancer. Expression of IGFBP-3 gene ascertained in all (except four) cases of ccRCC and in the majority of clippings from adjacent tissue. It was not found in kidneys from the control group. IGF-1, IGF-2, and IGFR-1 mRNA copy numbers in ccRCC were higher than in the material from the control group PMID:27358591

  20. Invasion and metastasis ability of renal cancer cell strains 786-0: under the influence of miR-141.

    PubMed

    Xu, Y; Lv, L N; Guo, Z Y; Zhang, W

    2016-01-01

    This study aimed to explore the invasion and metastasis ability of miR-141 in 786-0 renal cancer tissue cells, as well as identify the key function of endogenous miR-141 in adjustment and control of malignant activities of renal cancer. The renal cancer cell strain with overexpression of miR-141 and its control renal cancer cell line were constructed; methyl thiazolyl tetrazolium (MTT) assay was adopted to measure proliferation of renal cancer cells; Transwell assay was performed to measure the invasion and metastasis ability of cells; MTT assay and fluorescence activated cell sorting (FACS) were used for measurement of cell apoptosis and drug susceptibility. Results indicated that the expression of miR-141 in 786-0 cells could be significantly increased 400-fold by slow viruses that contained miR-141; moreover, c omprehensive functions showed that miR-141 inhibited the invasion and metastasis ability of renal cancer cells to a great extent (p less than 0.001), partially inhibited cell growth (p less than 0.05) and also induced cell cycle to be arrested in G0/G1 as well as reducing the number of cells in S phase (DNA replicative phase). Moreover, miR-141 could not induce morphologic changes of renal cancer cells, had no direct stimulating effect on cell apoptosis and could not improve the drug susceptibility of renal cancer cells to drugs such as cis-Dichlorodiamineplatinum (DDP), 5-fluorouracil (5-FU) and tumor-related apoptosis-inducing ligand (TRAIL). In conclusion, miR-141 can be considered an important cancer suppressor gene of renal cancer by inhibiting proliferation and metastasis of renal cancer cells. PMID:27358122

  1. Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma

    PubMed Central

    CAO, JINGYI; WANG, HAINAN; CHEN, FEIFEI; FANG, JIANZHENG; XU, AIMING; XI, WEI; ZHANG, SHENGLI; WU, GANG; WANG, ZENGJUN

    2016-01-01

    Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786-0 and Caki-1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E-cadherin and decreased expression levels of N-cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose-dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis. PMID:27035542

  2. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    PubMed

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with

  3. Quantitative analysis of interstitial mast cells in AA and AL renal amyloidosis.

    PubMed

    Danilewicz, Marian; Wagrowska-Danilewicz, Małgorzata

    2002-01-01

    Eighteen renal biopsy specimens obtained from patients with AA-type renal amyloidosis (AA) and 11 from patients with AL-type renal amyloidosis (AL), for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available, were examined quantitatively. The cases were selected on the basis of immunohistochemical studies. As a control, we used 10 biopsy specimens from the kidneys removed because of trauma. Morphometric investigations were carried out by a computer image analysis system to find an answer to the question of whether mast cells can correlate with tubulointerstitial fibrosis in AA and AL renal amyloidosis, and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression and interstitial infiltrates. The morphometric study revealed that the mean values of the interstitial tryptase-positive cells, expression of alpha-SMA, interstitial volume, CD68+, CD45RB+, CD43+ and CD20+ cells were increased in AA as compared with the AL group, most of them significantly. Most of these parameters were also significantly increased in both AA and AL patients as compared with the control group. In both the AA group and the AL group, there existed some significant positive correlations between interstitial tryptase-positive cells and interstitial expression of alpha-SMA, interstitial volume and CD68+ cells. Interestingly, in AA cases, but not in AL cases, we noted a significant relationship between interstitial tryptase-positive cells and CD43+ cells. Our findings demonstrate that mast cells belong to the constitutive cell types in the interstitium in renal amyloidosis, in particular in amyloid type A. In addition, in both the AA group and the AL group, the significant positive correlations between interstitial mast cell count and relative interstitial volume and interstitial expression of alpha-SMA suggest that these cells play a role in the development of interstitial

  4. Increased density of interstitial mast cells in amyloid A renal amyloidosis.

    PubMed

    Tóth, T; Tóth-Jakatics, R; Jimi, S; Takebayashi, S

    2000-09-01

    Renal interstitial fibrosis is the final common pathway leading to end-stage renal disease in various nephropathies including renal amyloidosis. However, the role of mast cells (MCs) in the fibrotic process of renal amyloidosis is not fully understood. We compared the distribution of MCs in renal biopsies from 30 patients with AA type renal amyloidosis and 20 control cases. Immunoreactivity of renal MCs to anti-tryptase and anti-chymase was studied. Interstitial myofibroblasts were stained with anti-alpha-smooth muscle actin (alpha-SMA) antibody, and inflammatory cells were identified by anti-CD45, -CD20, and -CD68 mAbs. Positively stained cells were counted, and the relative interstitial and fractional areas of anti-alpha-SMA stained cells were measured. Anti-CD29 mAb was used to detect beta1 integrin and anti-basic fibroblast growth factor (bFGF) mAb for the growth factor on MCs. MCs were rarely found in control samples. In contrast, samples showing amyloid deposition contained numerous tryptase-positive (MCT) (940.17 +/- 5.4 versus 6.74 +/- 1.1/mm2) but fewer chymase-positive (MCTC) cells (20.7 +/- 2.86 versus 1.7 +/- 0.76/mm2) in the renal interstitium. There was a significant relationship between interstitial MCT and creatinine clearance (r = -0.72), and between interstitial MCT and glomerular amyloid-index (GAI) (r = 0.723) and interstitial amyloid area (r = 0.824). Accumulation of MCs correlated significantly with the number of T lymphocytes (MCT: r = 0.694). There was also a significant relationship between mast cell (MC) number and the fractional area of alpha-SMA positive interstitium (r = 0.733) and interstitial fibrotic area (r = 0.6). Double immunostaining demonstrated intracytoplasmic presence of beta1 integrin on 87% of MCT and correlated significantly with the interstitial amyloid area (r = 0.818, P = .001) and T-cell number (r = 0.639, P = .002). bFGF was also detected on 85.5% of MCTC correlating well with the interstitial alpha-SMA-area (r = 0

  5. Selective suppression of Notch1 inhibits proliferation of renal cell carcinoma cells through JNK/p38 pathway.

    PubMed

    Wu, Kerong; Hu, Linkun; Hou, Jianquan

    2016-05-01

    The present study was performed to explore the effects of Notch1 inhibition selectively by siRNA on the proliferation and cell cycle of renal carcinoma cells. Human renal carcinoma cell lines, 786-0 and Caki-1, were treated with Si-Notch1 or negative control (NC). RT-PCR and western blotting were used to confirm the efficiency of siRNA on Notch1 expression. MTT, cell cycle analysis, colony formation as well as migration and invasion assays were performed. The expression levels of p38 and SAPK/JNK were measured by western blotting. For both cell lines, as compared with the NC group, the cell growth was markedly reduced, and colony formation was restricted in the Si-Notch1‑treated group. After incubated with Si-Notch1 or NC for 48 h, Si-Notch1-treated cells arrested the cell cycle at G1/S phase. The Si-Notch1 group also had a reduced rate of migration as well as invasion. Moreover, we observed a reduction in p-SAPK/JNK and p-p38 in Si-Notch1 transfected cells. The present study indicated that Notch signaling is important in the tumorigenesis of renal cell carcinoma. Notch1 may be a potential therapeutic regimen towards renal cell carcinoma, and JNK/p38 may serve as an important molecular mechanism for Notch1-mediated carcinogenesis. PMID:26986634

  6. Insulin Receptor Expression in Clear Cell Renal Cell Carcinoma and Its Relation to Prognosis

    PubMed Central

    Lkhagvadorj, Sayamaa; Oh, Sung Soo; Lee, Mi-Ra; Jung, Jae Hung; Chung, Hyun Chul; Cha, Seung-Kuy

    2014-01-01

    Purpose Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC). Materials and Methods Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. Results IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn't significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. Conclusion IR expression in CCRCC may be associated with favorable prognostic factors. PMID:24954312

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

    PubMed

    Mahajan, Ritesh; Mayappa, Nagaraj; Prashanth, V

    2016-09-01

    Sinonasal neoplasms are rare and exceptional site for metastatic tumours and comprising <3 % of all malignant aerodigestive tumours and <1 % of all malignancies. Renal cell carcinoma is known to metastasise to the most unusual sites, the sinonasal region being one of them. We here by present a case of 60 year old male patient who presented with epistaxis and nasal obstruction. Clinical examination and 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

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

    PubMed

    Fondriest, Sara A; Gowdy, John M; Goyal, Manish; Sheridan, Katherine C; Wasdahl, Daniel A

    2015-01-01

    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. PMID:27408652

  9. Renal Cell Protection of Erythropoietin beyond Correcting The Anemia in Chronic Kidney Disease Patients.

    PubMed

    Nasri, Hamid

    2014-01-01

    Currently many patients with chronic renal failure have profited from the use of erythropoietin to correct anemia (1,2). In chronic kidney disease, anemia is believed to be a surrogate index for tissue hypoxia that continues preexisting renal tissue injury (1-3). Erythropoietin is an essential glycoprotein that accelerates red blood cell maturation from erythroid progenitors and facilitates erythropoiesis. It is a 30.4 kD glycoprotein and class I cytokine containing 165 amino acids (3,4). Approximately 90% of systemic erythropoietin in adults is produced by peritubular interstitial fibroblasts in the renal cortex and outer medulla of the kidney (3-5). A feedback mechanism involving oxygen delivery to the tissues seems to regulate erythropoietin production. Hypoxia-inducible factor regulates transcription of the erythropoietin gene in the kidney, which determines erythropoietin synthesis (3-5). Erythropoietin is an essential glycoprotein that accelerates red blood cell maturation from erythroid progenitors and mediates erythropoiesis in the bone marrow (4-6). Kidney fibrosis is the last common pathway in chronic renal failure irrespective of the initial etiology (5,6). Constant inflammatory cell infiltration and pericyte-myofibroblast transition lead to renal fibrosis and insufficiency which result in decreased production of erythropoietin (4-7). Thus far, therapeutic efforts to treat patients with chronic renal failure by administering erythropoietin have been made only to correct anemia and putative hypoxic tissue damage. The introduction of recombinant human erythropoietin has marked a significant advance in the management of anemia associated with chronic renal failure (6-9). With an increasing number of patients with chronic renal failure receiving erythropoietin treatment, emerging evidence suggests that erythropoietin not only has an erythropoietic function, but also has renoprotective potential. In fact, in recent years, the additional non

  10. 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.

    PubMed

    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. PMID:21791489

  11. Successful Embolization of a Renal Artery Pseudoaneurysm with Arteriovenous Fistula and Extravasations Using Onyx After Partial Nephrectomy for Renal Cell Carcinoma

    SciTech Connect

    Zelenak, Kamil; Sopilko, Igor; Svihra, Jan; Kliment, Jan

    2009-01-15

    Partial nephrectomy can be associated with vascular complications. Computed tomography (CT) with CT angiography is ideal for noninvasive imaging of this process. The treatment of choice is selective embolization. Successful transcatheter embolization of right renal subsegmental artery pseudoaneurysm with arteriovenous fistula and extravasations using Onyx was performed in a 66-year-old woman with macrohematuria 12 days after partial nephrectomy for renal cell carcinoma.

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

    PubMed Central

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

    2015-01-01

    Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1), late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells. PMID:25874770

  13. ROTS: reproducible RNA-seq biomarker detector—prognostic markers for clear cell renal cell cancer

    PubMed Central

    Seyednasrollah, Fatemeh; Rantanen, Krista; Jaakkola, Panu; Elo, Laura L.

    2016-01-01

    Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression in various samples. The next step of rigorously quantifying differences between sample groups, however, still lacks well-defined best practices. Although a number of advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical utility in real biomedical studies. As a solution, we propose to use a data-adaptive procedure that selects an optimal statistic capable of maximizing reproducibility of detections. After demonstrating its improved sensitivity and specificity in a controlled spike-in study, the utility of the procedure is confirmed in a real biomedical study by identifying prognostic markers for clear cell renal cell carcinoma (ccRCC). In addition to identifying several genes previously associated with ccRCC prognosis, several potential new biomarkers among genes regulating cell growth, metabolism and solute transport were detected. PMID:26264667

  14. ROTS: reproducible RNA-seq biomarker detector-prognostic markers for clear cell renal cell cancer.

    PubMed

    Seyednasrollah, Fatemeh; Rantanen, Krista; Jaakkola, Panu; Elo, Laura L

    2016-01-01

    Recent comprehensive assessments of RNA-seq technology support its utility in quantifying gene expression in various samples. The next step of rigorously quantifying differences between sample groups, however, still lacks well-defined best practices. Although a number of advanced statistical methods have been developed, several studies demonstrate that their performance depends strongly on the data under analysis, which compromises practical utility in real biomedical studies. As a solution, we propose to use a data-adaptive procedure that selects an optimal statistic capable of maximizing reproducibility of detections. After demonstrating its improved sensitivity and specificity in a controlled spike-in study, the utility of the procedure is confirmed in a real biomedical study by identifying prognostic markers for clear cell renal cell carcinoma (ccRCC). In addition to identifying several genes previously associated with ccRCC prognosis, several potential new biomarkers among genes regulating cell growth, metabolism and solute transport were detected. PMID:26264667

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

  16. Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi

    PubMed Central

    Jongyotha, Kamonchanok; Sriphrapradang, Chutintorn

    2015-01-01

    We report on a 79-year-old woman with staghorn calculi who presented with severe hypercalcemia. She was later found to have humoral hypercalcemia of malignancy caused by a rare tumor, squamous cell carcinoma of the renal pelvis. Chronic irritation, infection and inflammation from staghorn stones cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. The prognosis is very poor, with a 5-year survival rate of <10%. This case highlights the importance of awareness of a very rare and aggressive carcinoma in a patient with long-standing nephrolithiasis. PMID:26557077

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

    SciTech Connect

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

    1984-03-01

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

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

    PubMed

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

    2016-06-01

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

  19. Ganglioside, disialosyl globopentaosylceramide (DSGb5), enhances the migration of renal cell carcinoma cells.

    PubMed

    Kawasaki, Yoshihide; Ito, Akihiro; Kakoi, Narihiko; Shimada, Shuichi; Itoh, Jun; Mitsuzuka, Koji; Arai, Yoichi

    2015-01-01

    About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no significant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the significantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no significant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability. PMID:25864532

  20. Therapeutic inhibition of mitochondrial function induces cell death in starvation-resistant renal cell carcinomas

    PubMed Central

    Isono, Takahiro; Chano, Tokuhiro; Yonese, Junji; Yuasa, Takeshi

    2016-01-01

    Renal cell carcinomas (RCC) have two types of cells for carbon metabolism and for cell signaling under nutrient-deprivation conditions, namely starvation-resistant and starvation-sensitive cells. Here, we evaluated the mitochondrial characteristics of these cell types and found that the resistant type possessed higher activities for both mitochondrial oxidative phosphorylation and glycolysis than the sensitive types. These higher activities were supported by the stored carbon, lipid and carbohydrate sources, and by a low level of mitochondrial reactive oxygen species (ROS) due to sustained SOD2 expression in the resistant RCC cells. In metastatic RCC cases, higher SOD2 expression was associated with a significantly shorter survival period. We found that treatment with the drugs etomoxir and buformin significantly reduced mitochondrial oxidative phosphorylation and induced cell death under glucose-deprivation conditions in starvation-resistant RCC cells. Our data suggest that inhibitory targeting of mitochondria might offer an effective therapeutic option for metastatic RCC that is resistant to current treatments. PMID:27157976

  1. Oxalate-induced changes in renal epithelial cell function: role in stone disease.

    PubMed

    Scheid, C; Honeyman, T; Kohjimoto, Y; Cao, L C; Jonassen, J

    2000-01-01

    Many studies on the etiology of stone disease have focused on the properties of urine that affect crystal nucleation and growth. More recent studies have focused on the properties of the renal epithelium and the role of injury in crystal retention. The latter studies have shown that oxalate exposure per se can damage renal epithelial cells and enhance crystal binding. This overview summarizes findings of specific biochemical and genetic alterations observed in renal epithelial cells after exposure to oxalate. In LLC-PK1 and MDCK cells, oxalate exposure produces marked effects on membranes, causing a redistribution of phosphatidylserine and activation of two lipid signaling cascades, one involving phospholipase A(2) (PLA(2)) and one involving ceramide. Longer exposure to oxalate leads to membrane damage and cell death. Adaptive responses are also observed, including proliferation (for replacement of damaged cells) and induction of various genes (for cellular replacement and repair). Many or all of these responses are blocked by antioxidants, and many can be mimicked by PLA(2) agonists/products. This finding suggests links between oxalate-induced increases in oxidant stress, lipid signaling pathways, and subsequent molecular responses that may eventuate in renal cell damage or death. Whether such changes play a role in stone disease in vivo, and whether strategies to inhibit these changes would be beneficial therapeutically, is unknown. PMID:11156705

  2. Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma

    PubMed Central

    Baldan, V; Griffiths, R; Hawkins, R E; Gilham, D E

    2015-01-01

    Background: Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. Methods: Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. Results: Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. Conclusion: TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population. PMID:25867267

  3. An Isolated Metastasis From Clear Cell Renal Cell Carcinoma to the Uterus: A Case Report and Review of Literature.

    PubMed

    Singh, Kamaljeet; DiSilvestro, Paul A; Lawrence, W Dwayne; Quddus, M Ruhul

    2016-09-01

    Ovaries are a favored site for metastatic tumors arising in the female genital tract. Other organs of the mullerian system, that is, the uterine corpus as well as the fallopian tubes, cervix, and the vagina are less commonly involved by metastases. If there is no clinical history of a known extramullerian primary tumor, suspicion that a uterine mass represents metastatic disease is low. We report the case of a renal clear cell carcinoma presenting as an isolated uterine mass and morphologically mimicking a primary endometrial clear cell adenocarcinoma. A review of the English literature yielded only a recent abstract describing 3 cases of renal clear cell carcinoma metastasizing to the endometrium. PMID:26630224

  4. Independent Tumor Origin in Two Cases of Synchronous Bilateral Clear Cell Renal Cell Carcinoma.

    PubMed

    Ji, Zhengguo; Zhao, Jialu; Zhao, Tian; Han, Yuying; Zhang, Yujun; Ye, Haihong

    2016-01-01

    Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs. PMID:27383411

  5. Independent Tumor Origin in Two Cases of Synchronous Bilateral Clear Cell Renal Cell Carcinoma

    PubMed Central

    Ji, Zhengguo; Zhao, Jialu; Zhao, Tian; Han, Yuying; Zhang, Yujun; Ye, Haihong

    2016-01-01

    Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs. PMID:27383411

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

    PubMed Central

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

    2005-01-01

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

  7. Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells.

    PubMed

    Mitsuoka, Keisuke; Shirasaka, Yoshiyuki; Fukushi, Akimasa; Sato, Masanobu; Nakamura, Toshimichi; Nakanishi, Takeo; Tamai, Ikumi

    2009-04-01

    L-Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L-citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L-citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L-Citrulline was transported in a Na(+)-dependent manner from the apical side of both cell types cultured on permeable supports with a microporous membrane. Kinetic analysis indicated that the transport involves two distinct Na(+)-dependent saturable systems and one Na(+)-independent saturable system in HK-2 cells. The uptake was competitively inhibited by neutral and cationic, but not anionic amino acids. Relatively large cationic and anionic compounds inhibited the uptake, but smaller ones did not. In HK-2 cells, mRNA expression of SLC6A19 and SLC7A9, which encode B(0)AT1 and b(0,+)AT, respectively, was detected by RT-PCR. In addition, L-citrulline transport was significantly decreased in HK-2 cells in which either SLC6A19 or SLC7A9 was silenced. Hence, these results suggest that amino acid transporters B(0)AT1 and b(0,+)AT are involved in the reabsorption of L-citrulline in the kidney, at least in part, by mediating the apical membrane transport of L-citrulline in renal tubule cells. PMID:19322909

  8. Epithelial Cell Repopulation and Preparation of Rodent Extracellular Matrix Scaffolds for Renal Tissue Development.

    PubMed

    Uzarski, Joseph S; Su, Jimmy; Xie, Yan; Zhang, Zheng J; Ward, Heather H; Wandinger-Ness, Angela; Miller, William M; Wertheim, Jason A

    2015-01-01

    This protocol details the generation of acellular, yet biofunctional, renal extracellular matrix (ECM) scaffolds that are useful as small-scale model substrates for organ-scale tissue development. Sprague Dawley rat kidneys are cannulated by inserting a catheter into the renal artery and perfused with a series of low-concentration detergents (Triton X-100 and sodium dodecyl sulfate (SDS)) over 26 hr to derive intact, whole-kidney scaffolds with intact perfusable vasculature, glomeruli, and renal tubules. Following decellularization, the renal scaffold is placed inside a custom-designed perfusion bioreactor vessel, and the catheterized renal artery is connected to a perfusion circuit consisting of: a peristaltic pump; tubing; and optional probes for pH, dissolved oxygen, and pressure. After sterilizing the scaffold with peracetic acid and ethanol, and balancing the pH (7.4), the kidney scaffold is prepared for seeding via perfusion of culture medium within a large-capacity incubator maintained at 37 °C and 5% CO2. Forty million renal cortical tubular epithelial (RCTE) cells are injected through the renal artery, and rapidly perfused through the scaffold under high flow (25 ml/min) and pressure (~230 mmHg) for 15 min before reducing the flow to a physiological rate (4 ml/min). RCTE cells primarily populate the tubular ECM niche within the renal cortex, proliferate, and form tubular epithelial structures over seven days of perfusion culture. A 44 µM resazurin solution in culture medium is perfused through the kidney for 1 hr during medium exchanges to provide a fluorometric, redox-based metabolic assessment of cell viability and proliferation during tubulogenesis. The kidney perfusion bioreactor permits non-invasive sampling of medium for biochemical assessment, and multiple inlet ports allow alternative retrograde seeding through the renal vein or ureter. These protocols can be used to recellularize kidney scaffolds with a variety of cell types, including vascular

  9. Epithelial Cell Repopulation and Preparation of Rodent Extracellular Matrix Scaffolds for Renal Tissue Development

    PubMed Central

    Uzarski, Joseph S.; Su, Jimmy; Xie, Yan; Zhang, Zheng J.; Ward, Heather H.; Wandinger-Ness, Angela; Miller, William M.; Wertheim, Jason A.

    2015-01-01

    This protocol details the generation of acellular, yet biofunctional, renal extracellular matrix (ECM) scaffolds that are useful as small-scale model substrates for organ-scale tissue development. Sprague Dawley rat kidneys are cannulated by inserting a catheter into the renal artery and perfused with a series of low-concentration detergents (Triton X-100 and sodium dodecyl sulfate (SDS)) over 26 hr to derive intact, whole-kidney scaffolds with intact perfusable vasculature, glomeruli, and renal tubules. Following decellularization, the renal scaffold is placed inside a custom-designed perfusion bioreactor vessel, and the catheterized renal artery is connected to a perfusion circuit consisting of: a peristaltic pump; tubing; and optional probes for pH, dissolved oxygen, and pressure. After sterilizing the scaffold with peracetic acid and ethanol, and balancing the pH (7.4), the kidney scaffold is prepared for seeding via perfusion of culture medium within a large-capacity incubator maintained at 37 °C and 5% CO2. Forty million renal cortical tubular epithelial (RCTE) cells are injected through the renal artery, and rapidly perfused through the scaffold under high flow (25 ml/min) and pressure (~230 mmHg) for 15 min before reducing the flow to a physiological rate (4 ml/min). RCTE cells primarily populate the tubular ECM niche within the renal cortex, proliferate, and form tubular epithelial structures over seven days of perfusion culture. A 44 µM resazurin solution in culture medium is perfused through the kidney for 1 hr during medium exchanges to provide a fluorometric, redox-based metabolic assessment of cell viability and proliferation during tubulogenesis. The kidney perfusion bioreactor permits non-invasive sampling of medium for biochemical assessment, and multiple inlet ports allow alternative retrograde seeding through the renal vein or ureter. These protocols can be used to recellularize kidney scaffolds with a variety of cell types, including vascular

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

    PubMed Central

    Papadimou, Evangelia; Morigi, Marina; Iatropoulos, Paraskevas; Xinaris, Christodoulos; Tomasoni, Susanna; Benedetti, Valentina; Longaretti, Lorena; Rota, Cinzia; Todeschini, Marta; Rizzo, Paola; Introna, Martino; Grazia de Simoni, Maria; Remuzzi, Giuseppe; Goligorsky, Michael S.; Benigni, Ariela

    2015-01-01

    Summary The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs), also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy. PMID:25754206

  11. Rare Co-existence of Squamous Cell Carcinoma with Infiltration of Renal Vein and Xanthogranulomatous Pyelonephritis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Nigam, L. K.; Trivedi, H. L.

    2015-01-01

    Primary renal squamous cell carcinoma is a very rare malignancy of the upper urinary tract. Most patients have history of chronic urolithiasis, analgesics abuse, radiotherapy or infection. Co-existence of SCC with xanthogranulomatous pyelonephritis is exceedingly rare with only few reports in the literature. We report a case of a 60-year-old male presented with right flank pain and mild tenderness of abdomen. Computed tomography of the abdomen revealed gross hydronephrosis with parenchymal thinning and irregular thick enhancing wall of pelvicalyceal system with multiple calculi in right kidney. Right renal vein appeared distended, filled with hypo dense material. Right nephrectomy was performed and sent for pathological examination. Histological evaluation revealed keratinizing squamous cell carcinoma with infiltration of renal vein and xanthogranulomatous pyelonephritis. PMID:26816904

  12. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    PubMed Central

    Wang, Jun; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. PMID:24350291

  13. Rare Co-existence of Squamous Cell Carcinoma with Infiltration of Renal Vein and Xanthogranulomatous Pyelonephritis.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Nigam, L K; Trivedi, H L

    2015-12-01

    Primary renal squamous cell carcinoma is a very rare malignancy of the upper urinary tract. Most patients have history of chronic urolithiasis, analgesics abuse, radiotherapy or infection. Co-existence of SCC with xanthogranulomatous pyelonephritis is exceedingly rare with only few reports in the literature. We report a case of a 60-year-old male presented with right flank pain and mild tenderness of abdomen. Computed tomography of the abdomen revealed gross hydronephrosis with parenchymal thinning and irregular thick enhancing wall of pelvicalyceal system with multiple calculi in right kidney. Right renal vein appeared distended, filled with hypo dense material. Right nephrectomy was performed and sent for pathological examination. Histological evaluation revealed keratinizing squamous cell carcinoma with infiltration of renal vein and xanthogranulomatous pyelonephritis. PMID:26816904

  14. Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

    ClinicalTrials.gov

    2012-11-07

    Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Follicular Lymphoma; Multiple Myeloma; NHL; Myeloproliferative Diseases; Chronic Myeloid Leukemia; Renal Cell Carcinoma; Aplastic Anemia

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

    SciTech Connect

    Nishikawa, Masaki; Yanagawa, Naomi; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto

    2012-01-13

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

  16. Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes

    PubMed Central

    Yun, Bo; Azad, Mohammad A. K.; Nowell, Cameron J.; Nation, Roger L.; Thompson, Philip E.; Roberts, Kade D.

    2015-01-01

    Polymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity. PMID:26392495

  17. Role of mitochondrial-derived oxidants in renal tubular cell cold storage injury

    PubMed Central

    Mitchell, Tanecia; Saba, Hamida; Laakman, Joe; Parajuli, Nirmala; MacMillan-Crow, Lee Ann

    2013-01-01

    Cold storage (CS) is regarded as a necessary procedure during donation of a deceased donor kidney that helps to optimize organ viability. Increased oxidant generation during both CS as well as during the reperfusion (or rewarming/CS.RW) phase have been suggested to be a major contributor to renal injury; although the source and/or biochemical pathways involved with oxidant production remain unclear. The purpose of this study was to determine if renal tubular mitochondrial superoxide is capable of inducing oxidant production and mitochondrial damage in response to a CS.RW insult. To test the role of mitochondrial superoxide in CS.RW injury, we used rat renal proximal tubular (NRK) cells overexpressing manganese superoxide dismutase (MnSOD), the major mitochondrial antioxidant. Oxidant production, mitochondrial membrane potential, respiratory complex function, and cell death were all altered following exposure of NRK cells to CS.RW. MnSOD overexpression or inhibition of nitric oxide synthase (NOS) provided significant protection against oxidant generation, respiratory complex inactivation, and cell death. These findings implicate mitochondrial superoxide, nitric oxide, and their reaction product, peroxynitrite, as key signaling molecules involved in CS.RW injury of renal tubular cells, and suggest that therapeutic inhibition of these pathways may protect the donor kidney. PMID:20659553

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

    SciTech Connect

    Mellas, J.; Hammerman, M.R.

    1986-03-01

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

  19. New Strategies in Renal Cell Carcinoma: Targeting the Genetic and Metabolic Basis of Disease

    PubMed Central

    Srinivasan, Ramaprasad; Ricketts, Christopher J.; Sourbier, Carole; Linehan, W. Marston

    2016-01-01

    The development of new forms of treatment of advanced renal cell carcinoma over the past two decades has been primarily focused on targeting the VHL/HIF pathway. The recent identification of mutations of chromatin remodeling genes in clear cell renal carcinoma (RCC), of genomic heterogeneity and of a Warburg-like metabolic phenotype in advanced disease has had a profound effect on our understanding of the evolution of clear cell RCC and on potential approaches to personalized therapy. Early approaches to therapy for patients with advanced type 1 papillary renal cell carcinoma that have centered around the MET/HGF pathway will expand as more genomic information becomes available. Sporadic and familial Type 2 papillary renal cell carcinoma are characterized by enhanced aerobic glycolysis and share an antioxidant response phenotype. In fumarate hydratase-deficient RCC, fumarate-induced succination of KEAP1 activates Nrf2 signaling. CUL3 and Nrf2 mutations as well as an Nrf2 activation phenotype are found in sporadic type 2 papillary RCC. Therapeutic approaches designed to target the Nrf2 pathway as well as to impair blood flow and glucose delivery in these cancers that are highly dependent on a robust tumor vasculature and on ready availability of glucose for energy production and glycolysis are in development. PMID:25564569

  20. Metastatic clear cell variant of renal cell carcinoma of the mandible: Review and case report

    PubMed Central

    Shah, Ajaz; Jahan, Shahi; Najar, Latief; Hassan, Shahid; Mohammad, Manzoor

    2016-01-01

    A case of metastatic renal cell carcinoma (RCC) to the mandible is reported. A 22-year-old man consulted us for hypoesthesia of the right lower lip. Panorama X-ray film showed a radiolucent lesion in the right mandibular body. A diagnosis of a metastatic tumor to the mandible from the right kidney was made after evaluation by computed tomography and bone scan with Tc99 methyl diphosphonate which also revealed multiple bone metastases. Histologically diagnosis was clear cell variant of RCC. Patient has been put on radiotherapy for symptomatic treatment and a molecularly targeted drug. The therapy effectively stopped the progressive growth of oral and other metastatic lesions. The quality of life is relatively well maintained with tolerable adverse effects. The patient is still on our follow-up with an improved quality of life.

  1. Metastatic clear cell variant of renal cell carcinoma of the mandible: Review and case report.

    PubMed

    Shah, Ajaz; Jahan, Shahi; Najar, Latief; Hassan, Shahid; Mohammad, Manzoor

    2016-01-01

    A case of metastatic renal cell carcinoma (RCC) to the mandible is reported. A 22-year-old man consulted us for hypoesthesia of the right lower lip. Panorama X-ray film showed a radiolucent lesion in the right mandibular body. A diagnosis of a metastatic tumor to the mandible from the right kidney was made after evaluation by computed tomography and bone scan with Tc99 methyl diphosphonate which also revealed multiple bone metastases. Histologically diagnosis was clear cell variant of RCC. Patient has been put on radiotherapy for symptomatic treatment and a molecularly targeted drug. The therapy effectively stopped the progressive growth of oral and other metastatic lesions. The quality of life is relatively well maintained with tolerable adverse effects. The patient is still on our follow-up with an improved quality of life. PMID:27563625

  2. Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload

    PubMed Central

    Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

    2016-01-01

    Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD. PMID:27545472

  3. Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload.

    PubMed

    Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

    2016-01-01

    Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD. PMID:27545472

  4. Importance of adenosine triphosphate in phospholipase A2-induced rabbit renal proximal tubule cell injury.

    PubMed Central

    Nguyen, V D; Cieslinski, D A; Humes, H D

    1988-01-01

    The pathogenesis of ischemic renal tubular cell injury involves a complex interaction of different processes, including membrane phospholipid alterations and depletion of high-energy phosphate stores. To assess the role of membrane phospholipid changes due to activation of phospholipases in renal tubule cell injury, suspensions enriched in rabbit renal proximal tubule segments were incubated with exogenous phospholipase A2 (PLA2). Exogenous PLA2 did not produce any significant change in various metabolic parameters reflective of cell injury in control nonhypoxic preparations despite a significant decrease in phosphatidylethanolamine (PE) and moderate increases in lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). In contrast, exogenous PLA2 treatment of hypoxic tubules resulted in a severe degree of cell injury, as demonstrated by marked declines in tubule K+ and ATP contents and significant decreases in tubule uncoupled respiratory rates, and was associated with significant phospholipid alterations, including marked declines in phosphatidylcholine (PC) and PE and significant rises in LPC, LPE, and free fatty acids (FFA). The injurious metabolic effects of exogenous PLA2 on hypoxic tubules were reversed by addition of ATP-MgCl2 to the tubules. The protective effect of ATP-MgCl2 was associated with increases in tubule PC and PE contents and declines in LPC, LPE, and FFA contents. These experiments thus indicate that an increase in exogenous PLA2 activity produces renal proximal tubule cell injury when cell ATP levels decline, at which point phospholipid resynthesis cannot keep pace with phospholipid degradation with resulting depletion of phospholipids and accumulation of lipid by-products. High-energy phosphate store depletion appears to be an important condition for exogenous PLA2 activity to induce renal tubule cell injury. PMID:3417866

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

    PubMed

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

    2015-05-01

    The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients. PMID:25563193

  6. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors.

    PubMed

    Swetha, G; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-02-01

    Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  7. Review of acquired cystic disease-associated renal cell carcinoma with focus on pathobiological aspects.

    PubMed

    Kuroda, Naoto; Ohe, Chisato; Mikami, Shuji; Hes, Ondrej; Michal, Michal; Brunelli, Matteo; Martignoni, Guido; Sato, Yasuharu; Yoshino, Tadashi; Kakehi, Yoshiyuki; Shuin, Taro; Lee, Gang-Hong

    2011-09-01

    Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently established entity. In this article, we introduce the general view of this new entity. Macroscopically, the disease exclusively occurs in ACD and may arise as a dominant mass or non-dominant masses. Histologically, the tumor is characterized by a microcystic pattern, neoplastic cells with an eosinophilic or oncocytic cytoplasm and frequent intratumoral oxalate crystal deposition. Prominent nucleoli of tumor cells are often observed. Immunohistochemically, neoplastic cells are generally positive for AMACR but negative for cytokeratin 7. Ultrastructurally, neoplastic cells contain abundant mitochondria in the cytoplasm. Genetically, the gain of chromosomes 3, 7, 17 and abnormality of the sex chromosome were frequently observed in several studies. In conclusion, ACD-associated RCC may be widely recognized as a distinct entity in the near future because this tumor is morphologically and genetically different from other renal tumor entities that have been previously established. PMID:21751153

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

    PubMed

    Weavers, Helen; Skaer, Helen

    2013-11-11

    Tissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative to one another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergent extension movements lengthen the tubule. Tip cell anchorage antagonizes forward-directed, TGF-β-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function. PMID:24229645

  9. Renal-type clear cell carcinoma of the prostate: A case report

    PubMed Central

    WANG, QIULAN; XUE, YONGJIE

    2015-01-01

    Renal-type clear cell carcinoma of the prostate is a rare and novel tumor that has only been identified in recent years. The present study describes a lesion in the prostate of a 64-year-old male with a two-year history of urinary frequency, urgency and difficulty, who was admitted to the San Ai Tang Hospital for benign prostatic hyperplasia, and subsequently underwent transurethral resection of the prostate. In total, 12 g of tissue was resected, which demonstrated morphological and immunohistochemical similarities to clear cell carcinoma of the kidney. Ultrasound inspection and computed tomography revealed prostate enlargement. Although no renal-enclosed mass was identified, metastatic lesions were revealed in the lungs, sternum and clavicles. In addition, right pleural thickening and a small amount of effusion in the pleural cavity were detected. Clear cell carcinoma was identified throughout the prostate, with surrounding regions of ordinary-type prostatic adenocarcinoma (Gleason score, 4+4). The urinary bladder exhibited no dysplasia or neoplasia. It was therefore concluded that the tumor represented a primary renal-type clear cell carcinoma that had arisen in the prostate. To the best of our knowledge, this type of extra-renal tumor has only been reported in three other previous studies. PMID:26137029

  10. MDCT imaging following nephrectomy for renal cell carcinoma: Protocol optimization and patterns of tumor recurrence

    PubMed Central

    Coquia, Stephanie F; Johnson, Pamela T; Ahmed, Sameer; Fishman, Elliot K

    2013-01-01

    The purpose of this pictorial essay is to review the common and uncommon sites of renal cell carcinoma recurrence throughout the body by examining their appearances on computerized tomography (CT). CT imaging protocols will be discussed. The sites of recurrence have been categorized into 4 groups: chest and mediastinum, abdomen and pelvis, musculoskeletal, and neurological. For each site of recurrence, a representative CT image correlate with discussion is provided. The unique CT appearance of renal cell carcinoma recurrence and how it can be used in lesion detection will be discussed. Renal cell carcinoma recurrences are hypervascular like the primary tumor, which can aid in not only lesion detection but also in some cases, differentiation from other primary tumors. Through CT case review of various sites of recurrence, lesions are shown to be easily seen on arterial phase while sometimes being nearly inconspicuous on venous or delayed phases. Coronal and sagittal reconstructions can also improve diagnostic sensitivity. CT is the most commonly used imaging tool for surveillance of renal cell carcinoma recurrence after nephrectomy. Knowledge of sites of recurrence as well as the utility of arterial phase imaging and multiplanar reconstructions will aid in optimizing detection of disease recurrence. PMID:24349648

  11. Inhibitory effects of tetradecanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures

    SciTech Connect

    Hagiwara, Masamichi; Nagakura, Kazuhiko; Ueno, Munehisa; Fisher, J.W. )

    1987-11-01

    A human renal carcinoma from a patient with an erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency the cultured cells formed multicellular hemicysts (domes) which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase in Ep levels in the culture medium after the cultures reached confluency, in parallel with an increase in dome formation. The phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a significant dose-related inhibitory effect on Ep production and dome formation in the renal carcinoma cell cultures, suggesting an important role of protein kinase C, the only known receptor for TPA, in inhibiting the expression of differentiated phenotypes in the renal carcinoma cells. These studies suggest a role of the inositol-lipid second messenger path and protein kinase C in the regulation of Ep production.

  12. Ureteropelvic junction obstruction and renal cell carcinoma in a patient with solitary functioning kidney

    PubMed Central

    Jeong, Young Beom; Ko, Oh Seok; Park, Hyung Sub; Cha, Jai Seong; Park, Seung Chol; Kim, Hyung Jin; Park, Jong Kwan; Shin, Yu Seob

    2016-01-01

    We present a case of ureteropelvic junction obstruction (UPJO) and renal cell carcinoma (RCC) in a solitary functioning kidney (SFK), managed by robot-assisted dismembered pyeloplasty with partial nephrectomy in a single stage. To our best knowledge, we report the first case of UPJO with RCC in a congenital SFK. PMID:27330578

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

    PubMed Central

    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. PMID:27579394

  14. Xp11.2 Translocation Renal Cell Carcinoma Diagnosed by Immunohistochemistry and Cytogenetics

    PubMed Central

    Dey, Biswajit; Badhe, Bhawana; Govindarajan, Krishna Kumar; Ramesh, Ranjith Arumbakkam

    2016-01-01

    Xp11.2 translocation renal cell carcinomas (TRCCs) are a group of neoplasms with distinct clinical, histopathological appearance, immunohistochemical, and cytogenetic profile. We report a case of Xp11.2 translocation TRCC in an 11-year-old male diagnosed based on immunohistochemistry and fluorescence in situ hybridization. PMID:27365924

  15. Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis.

    PubMed

    Beaton, Hayley; Andrews, Darrell; Parsons, Martin; Murphy, Mary; Gaffney, Andrew; Kavanagh, David; McKay, Gareth J; Maxwell, Alexander P; Taylor, Cormac T; Cummins, Eoin P; Godson, Catherine; Higgins, Debra F; Murphy, Paula; Crean, John

    2016-07-01

    Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis, and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and frizzled 7 (FzD7) expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative receptor of Wnt6. In vitro Wnt6 expression leads to de novo tubulogenesis in renal epithelial cells grown in three-dimensional culture. Importantly, Wnt6 rescued epithelial cell dedifferentiation in response to transforming growth factor-β (TGF-β); Wnt6 reversed TGF-β-mediated increases in vimentin and loss of epithelial phenotype. Wnt6 inhibited TGF-β-mediated p65-NF-κB nuclear translocation, highlighting cross talk between the two pathways. The critical role of NF-κB in the regulation of vimentin expression was confirmed in both p65(-/-) and IKKα/β(-/-) embryonic fibroblasts. We propose that Wnt6 is involved in epithelialization and loss of Wnt6 expression contributes to the pathogenesis of renal fibrosis. PMID:27122540

  16. Epoxyeicosatrienoic Acids Affect Electrolyte Transport in Renal Tubular Epithelial Cells: Dependence on Cyclooxygenase and Cell Polarity

    PubMed Central

    Nüsing, Rolf M.; Schweer, Horst; Fleming, Ingrid; Zeldin, Darryl C.; Wegmann, Markus

    2007-01-01

    We investigated the effects of epoxyeicosatrienoic acids (EETs) on ion transport in the polarized renal distal tubular cell line, MDCK C7. Of the four EET regioisomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) studied, only apical, but not basolateral, application of 5,6-EET increased short circuit current (Isc) with kinetics similar to those of arachidonic acid. The ion transport was blocked by preincubation with the cyclooxygenase inhibitor indomethacin or with the chloride channel blocker NPPB. Further, both a Cl−-free bath solution and the Ca2+ antagonist verapamil blocked 5,6-EET-induced ion transport. Although the presence of the PGE2 receptors EP2, EP3, and EP4 was demonstrated, apically added PGE2 was ineffective and basolaterally added PGE2 caused a different kinetics in ion transport compared to 5,6-EET. Moreover, PGE2 sythesis in MDCK C7 cells was unaffected by 5,6-EET treatment. GC/MS/MS analysis of cell supernatants revealed the presence of the biologically inactive 5,6-dihydroxy-PGE1 in 5,6-EET-treated cells, but not in control cells. Indomethacin suppressed the formation of 5,6-dihydroxy-PGE1. 5,6-epoxy-PGE1 the precursor of 5,6-dihydroxy-PGE1, caused a similar ion transport as 5,6-EET. Cytochrome P450 enzymes homolog to human CYP2C8, CYP2C9, and CYP2J2 protein were detected immunologically in the MDCK C7 cells. Our findings suggest that 5,6-EET affects Cl-transport in renal distal tubular cells independent of PGE2 but by a mechanism, dependent on its conversion to 5,6-epoxy-PGE1 by cyclooxygenase. We suggest a role for this P450 epoxygenase product in the regulation of electrolyte transport, especially as a saluretic compound acting from the luminal side of tubular cells in the mammalian kidney. PMID:17494091

  17. Epoxyeicosatrienoic acids affect electrolyte transport in renal tubular epithelial cells: dependence on cyclooxygenase and cell polarity.

    PubMed

    Nüsing, Rolf M; Schweer, Horst; Fleming, Ingrid; Zeldin, Darryl C; Wegmann, Markus

    2007-07-01

    We investigated the effects of epoxyeicosatrienoic acids (EETs) on ion transport in the polarized renal distal tubular cell line, Madin-Darby canine kidney (MDCK) C7. Of the four EET regioisomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) studied, only apical, but not basolateral, application of 5,6-EET increased short-circuit current (I(sc)) with kinetics similar to those of arachidonic acid. The ion transport was blocked by preincubation with the cyclooxygenase inhibitor indomethacin or with the chloride channel blocker NPPB. Furthermore, both a Cl(-)-free bath solution and the Ca(2+) antagonist verapamil blocked 5,6-EET-induced ion transport. Although the presence of the PGE(2) receptors EP2, EP3, and EP4 was demonstrated, apically added PGE(2) was ineffective and basolaterally added PGE(2) caused a different kinetics in ion transport compared with 5,6-EET. Moreover, PGE(2) synthesis in MDCK C7 cells was unaffected by 5,6-EET treatment. GC/MS/MS analysis of cell supernatants revealed the presence of the biologically inactive 5,6-dihydroxy-PGE(1) in 5,6-EET-treated cells, but not in control cells. Indomethacin suppressed the formation of 5,6-dihydroxy-PGE(1). 5,6-Epoxy-PGE(1), the precursor of 5,6-dihydroxy-PGE(1), caused a similar ion transport as 5,6-EET. Cytochrome P-450 enzymes homolog to human CYP2C8, CYP2C9, and CYP2J2 protein were detected immunologically in the MDCK C7 cells. Our findings suggest that 5,6-EET affects Cl(-) transport in renal distal tubular cells independent of PGE(2) but by a mechanism, dependent on its conversion to 5,6-epoxy-PGE(1) by cyclooxygenase. We suggest a role for this P450 epoxygenase product in the regulation of electrolyte transport, especially as a saluretic compound acting from the luminal side of tubular cells in the mammalian kidney. PMID:17494091

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

    PubMed

    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

  19. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway

    PubMed Central

    Song, Bin; Shu, Ying; Cui, Tianlei; Fu, Ping

    2015-01-01

    Hypoxia-inducible factor 1-alpha (HIF-1α) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF-1α. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1α were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF-1α protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1α could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway. PMID:26884975

  20. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway.

    PubMed

    Song, Bin; Shu, Ying; Cui, Tianlei; Fu, Ping

    2015-01-01

    Hypoxia-inducible factor 1-alpha (HIF-1α) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF-1α. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1α were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF-1α protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1α could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway. PMID:26884975

  1. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells.

    PubMed

    Tan, Thian Kui; Zheng, Guoping; Hsu, Tzu-Ting; Wang, Ying; Lee, Vincent W S; Tian, Xinrui; Wang, Yiping; Cao, Qi; Wang, Ya; Harris, David C H

    2010-03-01

    As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis. PMID:20075196

  2. Bone scintigraphy in the initial staging of patients with renal-cell carcinoma: concise communication

    SciTech Connect

    Rosen, P.R.; Murphy, K.G.

    1984-03-01

    The records of 40 consecutive patients who received bone scintigraphy in conjunction with the initial evaluation and staging of renal-cell carcinoma were reviewed to determine the role of bone imaging in this clinical context. Bone scintigrams were positive in three out of 40 patients at the time of diagnosis. In view of the low yield of bone imaging, it appears that routine scintigraphy is unwarranted in the absence of skeletal symptoms before the diagnosis of renal lesions. The presence of a positive bone image did not alter the indication for nephrectomy.

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

    PubMed

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

    2015-07-01

    We present a 66-year-old woman with 2 months of visual hallucinations, unintentional weight loss, and short-term memory decline, whose clinical presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent evaluation for a paraneoplastic etiology revealed a renal mass, which was resected and identified as clear cell renal carcinoma. The patient's clinical condition improved after resection of the mass. When patients present with incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of paraneoplastic neurological disorders, as early diagnosis and treatment of malignancy may lead to symptomatic improvement. PMID:25608740

  4. Identification of nephrotoxic compounds with embryonic stem-cell-derived human renal proximal tubular-like cells.

    PubMed

    Li, Yao; Kandasamy, Karthikeyan; Chuah, Jacqueline Kai Chin; Lam, Yue Ning; Toh, Wei Seong; Oo, Zay Yar; Zink, Daniele

    2014-07-01

    The kidney is a major target for drug-induced toxicity, and the renal proximal tubule is frequently affected. Nephrotoxicity is typically detected only late during drug development, and the nephrotoxic potential of newly approved drugs is often underestimated. A central problem is the lack of preclinical models with high predictivity. Validated in vitro models for the prediction of nephrotoxicity are not available. Major problems are related to the identification of appropriate cell models and end points. As drug-induced kidney injury is associated with inflammatory reactions, we explored the expression of inflammatory markers as end point for renal in vitro models. In parallel, we developed a new cell model. Here, we combined these approaches and developed an in vitro model with embryonic stem-cell-derived human renal proximal tubular-like cells that uses the expression of interleukin (IL)-6 and IL-8 as end points. The predictivity of the model was evaluated with 41 well-characterized compounds. The results revealed that the model predicts proximal tubular toxicity in humans with high accuracy. In contrast, the predictivity was low when well-established standard in vitro assays were used. Together, the results show that high predictivity can be obtained with in vitro models employing pluripotent stem cell-derived human renal proximal tubular-like cells. PMID:24495215

  5. Computerized image analysis of cell-cell interactions in human renal tissue by using multi-channel immunoflourescent confocal microscopy

    NASA Astrophysics Data System (ADS)

    Peng, Yahui; Jiang, Yulei; Liarski, Vladimir M.; Kaverina, Natalya; Clark, Marcus R.; Giger, Maryellen L.

    2012-03-01

    Analysis of interactions between B and T cells in tubulointerstitial inflammation is important for understanding human lupus nephritis. We developed a computer technique to perform this analysis, and compared it with manual analysis. Multi-channel immunoflourescent-microscopy images were acquired from 207 regions of interest in 40 renal tissue sections of 19 patients diagnosed with lupus nephritis. Fresh-frozen renal tissue sections were stained with combinations of immunoflourescent antibodies to membrane proteins and counter-stained with a cell nuclear marker. Manual delineation of the antibodies was considered as the reference standard. We first segmented cell nuclei and cell membrane markers, and then determined corresponding cell types based on the distances between cell nuclei and specific cell-membrane marker combinations. Subsequently, the distribution of the shortest distance from T cell nuclei to B cell nuclei was obtained and used as a surrogate indicator of cell-cell interactions. The computer and manual analyses results were concordant. The average absolute difference was 1.1+/-1.2% between the computer and manual analysis results in the number of cell-cell distances of 3 μm or less as a percentage of the total number of cell-cell distances. Our computerized analysis of cell-cell distances could be used as a surrogate for quantifying cell-cell interactions as either an automated and quantitative analysis or for independent confirmation of manual analysis.

  6. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

    PubMed Central

    Bousquet, Guilhem; Bouchtaoui, Morad El; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-01-01

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities. We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived. Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC. PMID:26002555

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

    PubMed Central

    Wu, Szu-Ying; Sung, Ping-Jyun; Chang, Ya-Ling; Pan, Shiow-Lin; Teng, Che-Ming

    2015-01-01

    Heteronemin is a bioactive marine sesterterpene isolated from the sponge Hyrtios sp. Previous reports have shown that heteronemin possesses anticancer activity. Here, heteronemin displayed cytotoxic effects against three human cancer cell lines (A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 1.57 μM by MTT assay and a GI50 value of 0.77 μM by SRB assay. Heteronemin initiates apoptotic cell death by downregulating Bcl-2 and Bcl-xL and upregulating Bax, leading to the disruption of the mitochondrial membrane potential and the release of cytochrome c from the mitochondria. These effects were associated with the activation of caspase-3/caspase-8/caspase-9, followed by PARP cleavage. Furthermore, heteronemin inhibited the phosphorylation of AKT signaling pathway and ERK and activated p38 and JNK. The specific inhibition of the p38 pathway by SB203580 or p38 siRNA treatment reversed the heteronemin-induced cytotoxicity and apoptotic signaling. Heteronemin also induced autophagy in A498 cells, and treatment with chloroquine (autophagy inhibitor) or SP600125 (JNK inhibitor) inhibited autophagy and increased heteronemin-induced cytotoxicity and apoptotic signaling. Taken together, this study proposes a novel treatment paradigm in which the combination of heteronemin and autophagy inhibitors leads to enhanced RCC cell apoptosis. PMID:26090440

  8. Hexavalent chromium induces expression of mesenchymal and stem cell markers in renal epithelial cells.

    PubMed

    Li, Wei-Jen; Yang, Cheng-Lin; Chow, Kuan-Chih; Kuo, Ting-Wei

    2016-02-01

    Cr(VI) causes severe kidney damage. The patient's renal function could gradually recover by spontaneous kidney regeneration. The molecular effect of Cr(VI) on recovery of kidney cells, however, has not been clearly elucidated. Here we show that Cr(VI) induces expression of mesenchymal and stem cell markers, cell markers, such as paxillin, vimentin, α-SMA, nanog, and CD133 of HK-2 cells. Moreover, Cr(VI) activates epithelial-to-mesenchymal transition (EMT). By revealing that levels of dihydrodiol dehydrogenase were promptly reduced following Cr(VI) challenge, our data suggested that DDH could be involved in a Cr(VI)-related oxidation to generate massive reactive oxygen species and H2 O2 , and to create intracellular hypoxia, which then increased levels of SUMO-1 activating enzyme subunit 2, and sumoylation of eukaryotic elongation factor-2, to mediate the subsequent molecular and cellular responses, e.g., expression of mesenchymal and stem cell markers. Pretreatment with vitamin C reduced Cr(VI)-related cellular effects. However, no evident effect was observed when vitamin C was added following Cr(VI) challenge. PMID:25620490

  9. Ovarian metastasis of clear cell renal cell carcinoma: A case report.

    PubMed

    Bauerová, Lenka; Dundr, Pavel; Fischerová, Daniela; Pešl, Michael; Zikán, Michal; Burgetová, Andrea

    2014-01-01

    We report on a 61-year-old woman with a history of right-sided nephrectomy for clear cell renal cell carcinoma (RCC) occurring 21 years ago; she currently presented with a bilateral ovarian tumour. Histologically, the tumour of both ovaries was clear cell carcinoma. Immunohistochemically, the tumour cells were positive for vimentin, RCC marker, epithelial membrane antigen, cytokeratin AE1/3 and CD10. Cytokeratin 7, CA125, HMWCK, estrogen and progesterone receptors were all negative. Based on the morphology and immunophenotype of the tumour, we established a diagnosis of late metastasis of RCC in the ovaries. A postoperative abdominal computed tomography scan, however, revealed a tumour mass solely in the left kidney, which had not been visible in the preoperative ultrasound. The patient underwent nephron-sparing surgery and a biopsy showed the tumour to be clear cell RCC. Metastasis of RCC to the ovaries is rare, and to the best of our knowledge, only 24 cases have been reported to date. However, due to the different treatments and prognosis, the distinction between a primary ovarian tumour and metastasis of RCC is important. PMID:24678363

  10. Dual tropism of HIV-1 envelopes derived from renal tubular epithelial cells of patients with HIV-associated nephropathy.

    PubMed

    Zerhouni-Layachi, Bouchra; Husain, Mohammad; Ross, Michael J; Marras, Daniele; Sunamoto, Masaaki; Liu, Xinyan; Klotman, Paul E; Klotman, Mary E

    2006-02-28

    The phenotype of HIV-1 gp120 envelope derived from renal epithelium and peripheral blood mononuclear cells (PBMC) of patients with HIV-associated nephropathy was investigated in vitro. Chimeric viruses were derived from kidney or blood and used to infect primary CD4+T cells, cell lines expressing single co-receptors and a renal epithelial cell line HPT-1. HIV-1 variants derived from renal epithelium were dual tropic whereas simultaneously derived viruses from PBMC were R5-tropic. Utilization of alternative co-receptors CCR3, BONZO and BOB, also differed. PMID:16470129

  11. Cytoplasmic Accumulation of Heterogeneous Nuclear Ribonucleoprotein K Strongly Promotes Tumor Invasion in Renal Cell Carcinoma Cells

    PubMed Central

    Otoshi, Taiyo; Tanaka, Tomoaki; Morimoto, Kazuya; Nakatani, Tatsuya

    2015-01-01

    Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a part of the ribonucleoprotein complex which regulates diverse biological events. While overexpression of hnRNP K has been shown to be related to tumorigenesis in several cancers, both the expression patterns and biological mechanisms of hnRNP K in renal cell carcinoma (RCC) cells remain unclear. In this study, we showed that hnRNP K protein was strongly expressed in selected RCC cell lines (ACHN, A498, Caki-1, 786–0), and knock-down of hnRNP K expression by siRNA induced cell growth inhibition and apoptosis. Based on immunohistochemical (IHC) analysis of hnRNP K expression in human clear cell RCC specimens, we demonstrated that there was a significant positive correlation between hnRNP K staining score and tumor aggressiveness (e.g., Fuhrman grade, metastasis). Particularly, the rate of cytoplasmic localization of hnRNP K in primary RCC with distant metastasis was significantly higher than that in RCC without metastasis. Additionally, our results indicated that the cytoplasmic distribution of hnRNP K induced by TGF-β stimulus mainly contributed to TGF-β-triggered tumor cell invasion in RCC cells. Dominant cytoplasmic expression of ectopic hnRNP K markedly suppressed the inhibition of invasion by knock-down of endogenous hnRNP K. The expression level of matrix metalloproteinase protein-2 was decreased by endogenous hnRNP K knock-down, and restored by ectopic hnRNP K. Therefore, hnRNP K may be a key molecule involved in cell motility in RCC cells, and molecular mechanism associated with the subcellular localization of hnRNP K may be a novel target in the treatment of metastatic RCC. PMID:26713736

  12. In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET

    PubMed Central

    Wong, Peter K.; Lee, Sze Ting; Murone, Carmel; Eng, John; Lawrentschuk, Nathan; Berlangieri, Salvatore U.; Pathmaraj, Kunthi; O’Keefe, Graeme J.; Sachinidis, John; Byrne, Amanda J.; Bolton, Damien M.; Davis, Ian D.; Scott, Andrew M.

    2014-01-01

    Objective(s): The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Methods: Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. Results: The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). Conclusion: There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology.

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

    SciTech Connect

    Kim, Ji-Hee; Lkhagvadorj, Sayamaa; Lee, Mi-Ra; Hwang, Kyu-Hee; Chung, Hyun Chul; Jung, Jae Hung; Cha, Seung-Kuy; Eom, Minseob

    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.

  14. Squamous Cell Carcinoma of the Renal Pelvis, A Rare Site for a Commonly Known Malignancy.

    PubMed

    Nachiappan, Murugappan; Litake, Manjusha Madhusudhan; Paravatraj, Varun Gautam; Sharma, Navil; Narasimhan, Aditya

    2016-01-01

    Chronic nephrolithiasis predisposes to squamous metaplasia and subsequently SCC which is a rare malignancy of the upper urinary tract. A 60-year-old woman with a long standing history of renal calculi presented with flank pain and fever. Investigations revealed a mass in the superior pole of a non functioning left kidney while the right kidney was sub optimally functioning, hydronephrotic and there was presence of bilateral staghorn calculi. Patient underwent decompression of right kidney by double j stenting and left radical nephrectomy that revealed well differentiated squamous cell carcinoma of renal pelvis. Most SCC of the renal pelvis present with advanced disease and dismal prognosis while our patient presented with localized disease without lymphatic and distant metastasis. Thus radical nephrectomy can be curative if the disease can be diagnosed at an earlier stage. This emphasizes the need of early treatment of nephrolithiasis to prevent the development of SCC and screening of patients with long standing staghorn calculi. PMID:26894122

  15. Post renal transplant pure red cell aplasia—is tacrolimus a culprit?

    PubMed Central

    Patil, Malagouda R.; Choudhury, Arpita Roy; Chohwanglim, Manong; Divyaveer, Smita; Mahajan, Chetan; Pandey, Rajendra

    2016-01-01

    Anemia is not uncommon in the post-renal transplant period and has been reported in up to 40% of renal transplant recipients. It is commonly due to drugs and infections. While post-transplantation anemia is usually due to graft dysfunction and drugs such as mycophenolate and cotrimoxazole, tacrolimus is an uncommon cause. Tacrolimus is usually not believed to be significantly myelosuppressive, but it can cause anemia due to thrombotic microangiopathy. A literature review shows a very small number of reported cases of pure red cell aplasia (PRCA) where tacrolimus seemed to be a causative agent. We report a case series of three renal transplant recipients who were on tacrolimus and presented with chronic transfusion requiring anemia due to PRCA. PMID:27478605

  16. Squamous Cell Carcinoma of the Renal Pelvis, A Rare Site for a Commonly Known Malignancy

    PubMed Central

    Litake, Manjusha Madhusudhan; Paravatraj, Varun Gautam; Sharma, Navil; Narasimhan, Aditya

    2016-01-01

    Chronic nephrolithiasis predisposes to squamous metaplasia and subsequently SCC which is a rare malignancy of the upper urinary tract. A 60-year-old woman with a long standing history of renal calculi presented with flank pain and fever. Investigations revealed a mass in the superior pole of a non functioning left kidney while the right kidney was sub optimally functioning, hydronephrotic and there was presence of bilateral staghorn calculi. Patient underwent decompression of right kidney by double j stenting and left radical nephrectomy that revealed well differentiated squamous cell carcinoma of renal pelvis. Most SCC of the renal pelvis present with advanced disease and dismal prognosis while our patient presented with localized disease without lymphatic and distant metastasis. Thus radical nephrectomy can be curative if the disease can be diagnosed at an earlier stage. This emphasizes the need of early treatment of nephrolithiasis to prevent the development of SCC and screening of patients with long standing staghorn calculi. PMID:26894122

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

    PubMed

    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

  18. Post renal transplant pure red cell aplasia-is tacrolimus a culprit?

    PubMed

    Patil, Malagouda R; Choudhury, Arpita Roy; Chohwanglim, Manong; Divyaveer, Smita; Mahajan, Chetan; Pandey, Rajendra

    2016-08-01

    Anemia is not uncommon in the post-renal transplant period and has been reported in up to 40% of renal transplant recipients. It is commonly due to drugs and infections. While post-transplantation anemia is usually due to graft dysfunction and drugs such as mycophenolate and cotrimoxazole, tacrolimus is an uncommon cause. Tacrolimus is usually not believed to be significantly myelosuppressive, but it can cause anemia due to thrombotic microangiopathy. A literature review shows a very small number of reported cases of pure red cell aplasia (PRCA) where tacrolimus seemed to be a causative agent. We report a case series of three renal transplant recipients who were on tacrolimus and presented with chronic transfusion requiring anemia due to PRCA. PMID:27478605

  19. Sarcomatoid Squamous Cell Carcinoma of the Renal Pelvis Masquerading as Emphysematous Pyelonephritis with Staghorn Calculus

    PubMed Central

    Kivlin, Dana; Tong, Carmen; Friedlander, Justin; Perosio, Patricia

    2016-01-01

    Abstract Background: Staghorn calculi are well-established risk factors for recurrent urinary tract infections (UTIs) and subsequent renal deterioration. Less commonly, long-term urothelial irritation from a calculus may also pose a risk of malignant transformation. Case Presentation: A 77-year-old male with multiple medical comorbidities presented with a chronic right renal pelvic staghorn calculus and findings concerning for emphysematous pyelonephritis. He was subsequently taken to the operating room for a planned laparoscopic right nephrectomy. Final pathology analysis revealed sarcomatoid squamous cell carcinoma (SCC) of the renal pelvis with superimposed pyelonephritis and renal abscesses. Preoperative imaging was not suggestive of malignancy. Conclusion: Although SCC of the urothelium can be caused by chronic irritation, its presentation is usually isolated to the lower urinary tract and is rarely encountered in the renal pelvis. Our patient's presentation with sarcomatoid SCC is an even rarer entity. Chronic staghorn calculi must be considered as a potential risk factor for the development of both UTI and malignant urothelial transformation.

  20. Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?

    PubMed Central

    2013-01-01

    Background Single circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC. Methods Blood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH. Results CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX. Conclusions The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer. PMID:24044779

  1. 20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease

    PubMed Central

    Park, Frank; Sweeney, William E.; Jia, Guangfu; Roman, Richard J.; Avner, Ellis D.

    2008-01-01

    Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts. PMID:18596124

  2. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    SciTech Connect

    Huang, J.-S. Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-12-01