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https://www.readbyqxmd.com/read/28329682/the-swi-snf-protein-pbrm1-restrains-vhl-loss-driven-clear-cell-renal-cell-carcinoma
#1
Amrita M Nargund, Can G Pham, Yiyu Dong, Patricia I Wang, Hatice U Osmangeyoglu, Yuchen Xie, Omer Aras, Song Han, Toshinao Oyama, Shugaku Takeda, Chelsea E Ray, Zhenghong Dong, Mathieu Berge, A Ari Hakimi, Sebastien Monette, Carl L Lekaye, Jason A Koutcher, Christina S Leslie, Chad J Creighton, Nils Weinhold, William Lee, Satish K Tickoo, Zhong Wang, Emily H Cheng, James J Hsieh
PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327411/gas6-axl-signaling-in-presence-of-sunitinib-is-enhanced-diversified-and-sustained-in-renal-tumor-cells-resulting-in-tumor-progressive-advantages
#2
Anna Gustafsson, Helena K M Fritz, Björn Dahlbäck
Clear Cell Renal Cell Carcinoma (CCRCC) is a lethal cancer with bad prognosis due to development of chemoresistance and recurrence of more aggressive tumors. Investigation of Gas6-mediated Axl signaling in CCRCC and endothelial cells reveals a Sunitinib resistant Gas6-Axl signaling that is sustained and enhanced and specifically triggers downstream AKT and PRAS40 activation in an intensified manner. Gas6-induced Axl signaling in presence of Sunitinib is also diversified displaying onset of Axl-dependent EGFR and METR activation and activation of classical MAPK pathways...
March 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28327152/trim8-restores-p53-tumour-suppressor-function-by-blunting-n-myc-activity-in-chemo-resistant-tumours
#3
Francesca Mastropasqua, Flaviana Marzano, Alessio Valletti, Italia Aiello, Giuseppe Di Tullio, Annalisa Morgano, Sabino Liuni, Elena Ranieri, Luisa Guerrini, Giuseppe Gasparre, Elisabetta Sbisà, Graziano Pesole, Antonio Moschetta, Mariano Francesco Caratozzolo, Apollonia Tullo
BACKGROUND: TRIM8 plays a key role in controlling the p53 molecular switch that sustains the transcriptional activation of cell cycle arrest genes and response to chemotherapeutic drugs. The mechanisms that regulate TRIM8, especially in cancers like clear cell Renal Cell Carcinoma (ccRCC) and colorectal cancer (CRC) where it is low expressed, are still unknown. However, recent studies suggest the potential involvement of some microRNAs belonging to miR-17-92 and its paralogous clusters, which could include TRIM8 in a more complex pathway...
March 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28327121/bap1-and-pbrm1-in-metastatic-clear-cell-renal-cell-carcinoma-tumor-heterogeneity-and-concordance-with-paired-primary-tumor
#4
Jeanette E Eckel-Passow, Daniel J Serie, John C Cheville, Thai H Ho, Payal Kapur, James Brugarolas, R Houston Thompson, Bradley C Leibovich, Eugene D Kwon, Richard W Joseph, Alexander S Parker
BACKGROUND: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. MATERIALS AND METHODS: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients...
March 21, 2017: BMC Urology
https://www.readbyqxmd.com/read/28288504/clear-cell-renal-cell-carcinoma-with-intratumoral-granulomatous-reaction-a-case-report-and-review-of-the-literature
#5
Hayeon Kim, Jong Wook Kim, Aeree Kim, Hyeyoon Chang
Granulomatous reaction associated with clear cell renal cell carcinoma (CCRCC) is a rare finding, and only a few cases have been described in the literature. It is postulated to occur due to cancer-related antigenic factors such as cancer cells themselves or soluble tumor antigens shed into the blood. Herein, we describe a case of a 56-year-old male patient diagnosed with CCRCC with intratumoral granulomatous inflammation.
March 14, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28287633/increased-vasohibin-1-expression-is-associated-with-metastasis-and-poor-prognosis-of-renal-cell-carcinoma-patients
#6
Shuji Mikami, Mototsugu Oya, Takeo Kosaka, Ryuichi Mizuno, Yasumasa Miyazaki, Yasufumi Sato, Yasunori Okada
The microvascular density detected by markers of endothelial cells (ECs), such as CD31 and CD34, is considered to be a biomarker for angiogenesis, and it is generally associated with the malignant potential of solid tumors. However, there is a conflicting relationship between the microvascular density and prognosis in clear-cell renal cell carcinoma (ccRCC) patients. It may be explained by the suggestion that the microvascular density cannot fully reflect the angiogenic activity in ccRCC, as the markers of ECs are expressed by both quiescent and activated ECs...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28284893/gstm1-genotype-is-an-independent-prognostic-factor-in-clear-cell-renal-cell-carcinoma
#7
Vesna M Coric, Tatjana P Simic, Tatjana D Pekmezovic, Gordana M Basta-Jovanovic, Ana R Savic-Radojevic, Sanja M Radojevic-Skodric, Marija G Matic, Sonja R Suvakov, Dejan P Dragicevic, Tanja M Radic, Zoran M Dzamic, Marija S Pljesa-Ercegovac
PURPOSE: Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). METHODS: GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only...
March 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28284891/loss-of-bap1-protein-expression-in-the-first-metastatic-site-predicts-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#8
Yuji Miura, Naoko Inoshita, Masaomi Ikeda, Yu Miyama, Ryosuke Oki, Suguru Oka, Chihiro Kondoh, Yukinori Ozaki, Yuko Tanabe, Kazuhiro Kurosawa, Shinji Urakami, Tadasu Kohno, Toshikazu Okaneya, Toshimi Takano
OBJECTIVES: To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. METHODS AND MATERIALS: We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins...
March 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28280876/quantitative-computer-aided-diagnostic-algorithm-for-automated-detection-of-peak-lesion-attenuation-in-differentiating-clear-cell-from-papillary-and-chromophobe-renal-cell-carcinoma-oncocytoma-and-fat-poor-angiomyolipoma-on-multiphasic-multidetector-computed
#9
Heidi Coy, Jonathan R Young, Michael L Douek, Matthew S Brown, James Sayre, Steven S Raman
OBJECTIVE: To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). MATERIALS AND METHODS: We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]...
March 9, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28280347/high-expression-of-aldolase-a-predicts-poor-survival-in-patients-with-clear-cell-renal-cell-carcinoma
#10
Ning Na, Heng Li, Chengfang Xu, Bin Miao, Liangqing Hong, Zhengyu Huang, Qiu Jiang
BACKGROUND: Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients. METHODS: The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28278333/adjuvant-treatment-for-high-risk-clear-cell-renal-cancer-updated-results-of-a-high-risk-subset-of-the-assure-randomized-trial
#11
Naomi B Haas, Judith Manola, Janice P Dutcher, Keith T Flaherty, Robert G Uzzo, Michael B Atkins, Robert S DiPaola, Toni K Choueiri
Importance: Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date...
March 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#12
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28270206/meis1-inhibits-clear-cell-renal-cell-carcinoma-cells-proliferation-and-in-vitro-invasion-or-migration
#13
Jie Zhu, Liang Cui, Axiang Xu, Xiaotao Yin, Fanglong Li, Jiangping Gao
BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28269753/lncrna-neat1-is-a-prognosis-biomarker-and-regulates-cancer-progression-via-epithelial-mesenchymal-transition-in-clear-cell-renal-cell-carcinoma
#14
Li Ning, Zhiguo Li, Dianjun Wei, Haiyan Chen, Chao Yang
BACKGROUND: The long non-coding RNAs (lncRNAs) are emerging as important regulators in cancer progression. Clear cell renal cell carcinoma (ccRCC) is one of the most common urological cancers with poor prognosis. In this study, we examined the functional role of the lncRNA, nuclear enriched abundant transcript 1 (NEAT1) in ccRCC progression. METHODS: We performed quantitative real time PCR and western blotting assays to measure mRNA and protein expression levels, respectively...
February 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28266251/an-integrated-analysis-of-cancer-genes-in-clear-cell-renal-cell-carcinoma
#15
Jin Li, Liping Guo, Zisheng Ai
AIM: This study was performed to detect driver genes and implement integrated analyses on these drivers in clear cell renal cell carcinoma (ccRCC). METHODS: Driver genes and pathways were predicted by OncodriveFM and Dendrix using 39,636 somatic mutations from The Cancer Genome Atlas, followed by DNA methylation, copy number variation, differential expression and survival analyses. RESULTS: Overall, 342 driver genes and 106 pathways were determined by OncodriveFM, two driver genes by Dendrix...
April 2017: Future Oncology
https://www.readbyqxmd.com/read/28261513/primary-clear-cell-microcystic-adenoma-of-the-sinonasal-cavity-pathological-or-fortuitous-association
#16
Rosalin Cooper, Hannah Markham, Jeffery Theaker, Adrian Bateman, David Bunyan, Matthew Sommerlad, Gillian Crawford, Diana Eccles
Primary clear cell microcystic adenoma of the sinonasal cavity is rare. It has previously been described only as a VHL-associated tumour. Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome characterised by an elevated risk of neoplasia including clear cell renal cell carcinoma (ccRCC), haemangioblastoma, and phaeochromocytoma. We describe the second reported case of a primary clear cell microcystic adenoma of the sinonasal cavity. The 39-year-old patient with VHL syndrome had previously undergone resection and ablation of ccRCC...
2017: Case Reports in Pathology
https://www.readbyqxmd.com/read/28260718/loss-of-setd2-but-not-h3k36me3-correlates-with-aggressive-clinicopathological-features-of-clear-cell-renal-cell-carcinoma-patients
#17
Lei Liu, Renbo Guo, Xiang Zhang, Yiran Liang, Feng Kong, Jue Wang, Zhonghua Xu
Recent studies facilitated by DNA sequencing identified the histone modifying gene SETD2 as the second most frequent mutant gene in sporadic clear cell renal cell carcinoma (ccRCC) patients. SETD2 functions as a tumor suppressor in ccRCC. However, its clinical association and biological functions are not fully delineated. The aim of this study is to evaluate the clinical significance of SETD2 in ccRCC patients. SETD2 and its canonical histone modification product H3K36me3 were analyzed by immunohistochemistry (IHC) in 155 ccRCC patients from two independent cohorts retrospectively...
March 6, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28259286/targeting-hif-2-%C3%AE-in-clear-cell-renal-cell-carcinoma-a-promising-therapeutic-strategy
#18
REVIEW
Olga Martínez-Sáez, Pablo Gajate Borau, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Enrique Grande
The loss of the Von Hippel-Lindau tumor suppressor (VHL) is a key oncogenic event in the vast majority of patients with clear cell renal cell carcinoma (ccRCC). With the loss of the VHL protein (pVHL) function, the hypoxia inducible factor α (HIF-α) accumulates inside the tumor cell and dimerizes with HIF-β. The HIF-α/HIF-β complex transcriptionally activates hundreds of genes promoting the adaptation to hypoxia that is implicated in tumor development. There is growing evidence showing that HIF-2α subunit has a central role in ccRCC over HIF-1α...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28257806/pseudohypoxia-induced-by-mir-126-deactivation-promotes-migration-and-therapeutic-resistance-in-renal-cell-carcinoma
#19
Weijun Liu, Hanxiang Chen, Nathan Wong, Wesley Haynes, Callie M Baker, Xiaowei Wang
Pseudohypoxia plays a central role in the progression and therapeutic resistance of clear cell renal cell carcinoma (ccRCC); however, the underlying mechanisms are poorly understood. MicroRNA miR-126 has decreased expression in metastatic or relapsed ccRCC as compared to primary tumors, but the mechanisms by which miR-126 is implicated in RCC remain unknown. Through RNA-seq profiling to evaluate the impact of overexpression or CRISPR knockout of miR-126, we have identified SERPINE1 as a miR-126-5p target regulating cell motility, and SLC7A5 as a miR-126-3p target regulating the mTOR/HIF pathway...
February 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28256713/intrinsic-gene-changes-determine-the-successful-establishment-of-stable-renal-cancer-cell-lines-from-tumour-tissue
#20
Hailiang Feng, Yu Zhang, Kan Liu, Yan Zhu, Zhenli Yang, Xu Zhang, Yuqin Liu
Human tumour cell lines, especially those with complete data and follow-up, are important tools in tumour biological studies. Clear cell renal cell cancer (ccRCC) is not sensitive to radiotherapy or chemotherapy, and treatment of patients with distant metastasis relies on targeted therapy. Here, we report the establishment of 7 new ccRCC stable cell lines that were continuously cultured for more than 20 generations after selection from samples of 81 cases of renal cell cancer. Moreover, gene expression and methylation in the established cell lines, in those that had a finite in vitro life span of less than 10 generations, and in cells that originated from the same culture at different generations were profiled using microarrays...
March 3, 2017: International Journal of Cancer. Journal International du Cancer
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