scholarly journals Limited Association Between Ascorbate Concentrations and Vitamin C Transporters in Renal Cell Carcinoma Cells and Clinical Samples

2021 ◽  
Vol 55 (5) ◽  
pp. 553-568
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Culture ◽  
Vitamin C ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Whole Body ◽  
Clinical Samples ◽  
Cytoplasmic Staining ◽  
Cellular Location ◽  
Protein Levels

BACKGROUND/AIMS: Maintenance of whole-body ascorbate levels and distribution is mediated via sodium-dependent vitamin C transporters (SVCTs). The kidney is one of a few organs that express both SVCT1 and SVCT2. Recent evidence suggests that accumulation of ascorbate may be different in tumour compared to normal tissue, but data on SVCT levels in tumours is sparse. METHODS: The role of the two SVCT isoforms in ascorbate uptake in renal cell carcinoma (RCC) was investigated in vitro and in clinical samples. In three human RCC cell lines, we investigated SVCT protein levels and cellular location in response to ascorbate supplementation and withdrawal. In clinical RCC samples (n=114), SVCT patterns of staining and protein levels were analysed and compared to ascorbate levels. RESULTS: In cell culture, transporter levels and cellular location were not modified by ascorbate availability at any time up to 8h, although basal SVCT2 levels governed maximal ascorbate accumulation. In clinical samples, SVCT1 protein levels in papillary RCC (pRCC) were similar to matched normal renal cortex, but were increased in clear-cell RCC (ccRCC). Native SVCT2 (72 kDa) was significantly decreased in both pRCC and ccRCC tissues compared to cortex (p<0.01), whereas a modified form of SVCT2 (100 kDa) was significantly increased (p<0.001). There was no association between the transporters (SVCT1, native or modified SVCT2) and ascorbate concentrations in either normal or tumour tissues. SVCT1 and SVCT2 displayed diffuse cytoplasmic staining in both pRCC and ccRCC tumour cells, with cortex showing distinct membrane staining for SVCT1. CONCLUSION: We observed a re-distribution of ascorbate transporters in tumour tissue compared to normal cortex and a shift from native to modified SVCT2 in cell culture and clinical samples. Data presented here show that SVCT protein levels do not appear to predict intracellular ascorbate accumulation in RCC.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Carlos Zamarrón ◽  
Ihab Abdulkader ◽  
María C. Areses ◽  
Vanesa García-Paz ◽  
Luís León ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Factor ◽  
Thyroid Gland ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Growth Factor Receptor ◽  
Follicular Adenoma ◽  
Distant Metastases ◽  
Whole Body ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (CCRCC) is the most common origin for metastasis in the thyroid. A 51-year-old woman was referred to our hospital for a subcarinal lesion. Ten years before, the patient had undergone a nephrectomy for CCRCC. Whole-body fluorodeoxyglucose positron emission tomography revealed elevated values in the thyroid gland, while the mediastinum was normal. An endoscopic ultrasonography-guided fine-needle aspiration biopsy of the mediastinal mass was consistent with CCRCC, and this was confirmed after resection. The thyroidectomy specimen also revealed lymphocytic thyroiditis, nodular hyperplasia, one follicular adenoma, two papillary microcarcinomas, and six foci of metastatic CCRCC involving both thyroid lobes. Curiously two of the six metastatic foci were located inside two adenomatoid nodules (tumor-in-tumor). The metastatic cells were positive for cytokeratins, CD10, epidermal growth factor receptor, and vascular endothelial growth factor receptor 2. NoBRAFgene mutations were found in any of the primary and metastatic lesions. The patient was treated with sunitinib and finally died due to CCRCC distant metastases 6 years after the thyroidectomy. In CCRCC patients, a particularly prolonged survival rate may be achieved with the appropriate therapy, in contrast to the ominous prognosis typically found in patients with thyroid metastases from other origins.

scholarly journals MP14-01 PREDICTIVE IMPACT OF AN EARLY CHANGE IN SERUM C-REACTIVE PROTEIN LEVELS IN NIVOLUMAB THERAPY FOR METASTATIC RENAL CELL CARCINOMA

2020 ◽  
Vol 203 ◽  
pp. e194
Author(s):  
Hiroki Ishihara* ◽  
Toshio Takagi ◽  
Tsunenori Kondo ◽  
Hironori Fukuda ◽  
Hidekazu Tachibana ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
C Reactive Protein ◽  
Early Change ◽  
Protein Levels ◽  
Reactive Protein

scholarly journals Acyl-CoA Thioesterase 8 and 11 as Novel Biomarkers for Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Chao-Liang Xu ◽  
Lei Chen ◽  
Deng Li ◽  
Fei-Teng Chen ◽  
Ming-Lei Sha ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Correlation Analysis ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Functional Enrichment ◽  
Clinical Samples ◽  
Cell Renal Cell Carcinoma ◽  
Ccrcc Cell

BackgroundClear cell renal cell carcinoma (ccRCC) is essentially a metabolic disorder characterized by reprogramming of several metabolic pathways. Acyl-coenzyme A thioesterases (ACOTs) are critical enzymes involved in fatty acid metabolism; however, the roles of ACOTs in ccRCC remain unclear. This study explored ACOTs expressions and their diagnostic and prognostic values in ccRCC.MethodsThree online ccRCC datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were utilized to measure the expressions of ACOTs in paired normal and tumor tissues. Receiver operating characteristic (ROC) curves were depicted to assess the diagnostic values of ACOTs in ccRCC. Quantitative real-time PCR and immunohistochemical analysis were performed to validate the ACOT11 expression in ccRCC cell lines and clinical samples. Survival curves and Cox regression analysis were used to evaluate the predictive values of ACOTs in clinical outcome of ccRCC patients. Functional enrichment analyses and correlation analysis were carried out to predict the potential roles of ACOT8 in tumorigenesis and progression of ccRCC.ResultsACOT1/2/8/11/13 were found to be significantly downregulated in ccRCC samples. In particular, ACOT11 was decreased in almost every matched normal-tumor pair, and had extremely high diagnostic value as shown by ROC curve analysis (AUC = 0.964). The expression of ACOT11 was further verified in ccRCC cell lines and clinical samples at mRNA and protein levels. Furthermore, clinical correlation analysis and survival analysis indicated that ACOT8 was correlated with disease progression and was an independent predictor of unfavorable outcome in ccRCC. Moreover, functional analyses suggested potential roles of ACOT8 in the regulation of oxidative phosphorylation (OXPHOS), and correlation analysis revealed an association between ACOT8 and ferroptosis-related genes in ccRCC.ConclusionOur study revealed that ACOT11 and ACOT8 are promising biomarkers for diagnosis and prognosis of ccRCC, respectively, and ACOT8 may affect ccRCC development and progression through the regulation of OXPHOS and ferroptosis. These findings may provide new strategies for precise diagnosis and personalized therapy of ccRCC.

Ceruloplasmin expression in renal cell carcinoma correlates with higher-grade and shortened survival

2021 ◽  
Author(s):  
Annette Zimpfer ◽  
Änne Glass ◽  
Manuela Bastian ◽  
Peter Schuff-Werner ◽  
Oliver W Hakenberg ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Survival Rate ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
High Grade ◽  
Overall Survival Rate ◽  
Rank Tests ◽  
Cell Renal Cell Carcinoma ◽  
Protein Levels

Aim: We aimed to explore ceruloplasmin (CP) expression in clear cell renal cell carcinoma (ccRCC). Materials & methods: CP was analyzed in biofluid samples of 63 ccRCC patients, divided into three grading groups, and immunohistochemically, in 308 ccRCC. Results: Significant differences of mean plasma and urine CP levels in different grading groups were found. CP immunoreactivity was significantly linked to high-grade disease. Log rank tests showed a significant shorter overall survival rate in CP-positive cases (all p < 0.05). Conclusion: CP protein levels in biofluid samples confirmed differential CP expressions, depending on nuclear grade in ccRCC as previously seen in RNA expression analysis. CP expression was linked to high-grade disease and reduced survival rate in RCC.

Increased intake of fruits and vegetables high in vitamin C and fibre is associated with decreased risk of renal cell carcinoma in the US

2008 ◽  
Vol 6 (9) ◽  
pp. 103
Author(s):  
K. Brock ◽  
G. Gridley ◽  
B.C. Chiu ◽  
A.G. Ershow ◽  
C.F. Lynch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Vitamin C ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Fruits And Vegetables ◽  
The Us

Predictive impact of an early change in serum C-reactive protein levels in nivolumab therapy for metastatic renal cell carcinoma

2020 ◽  
Vol 38 (5) ◽  
pp. 526-532 ◽  
Author(s):  
Hiroki Ishihara ◽  
Toshio Takagi ◽  
Tsunenori Kondo ◽  
Hironori Fukuda ◽  
Hidekazu Tachibana ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
C Reactive Protein ◽  
Early Change ◽  
Protein Levels ◽  
Reactive Protein

scholarly journals Integrative analysis reveals CRHBP inhibits renal cell carcinoma progression by regulating inflammation and apoptosis

2019 ◽  
Vol 27 (7-8) ◽  
pp. 607-618 ◽  
Author(s):  
Kang Yang ◽  
Yusha Xiao ◽  
Tao Xu ◽  
Weimin Yu ◽  
Yuan Ruan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Gene Expression Omnibus ◽  
Integrative Analysis ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Apoptotic Pathway

Abstract Patients with renal cell carcinoma (RCC) usually develop drug resistance and have poor prognosis owing to its insensitive property. However, the underlying mechanisms of RCC are still unclear. We implemented an integrative analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets. Three genes (CRHBP, RAB25 and PSAT1) were found to be potential biomarkers in ccRCC and validated by four independent cohorts. Then, ccRCC patients with a decreased expression of CRHBP in tumor tissues had significantly poor survival by TCGA ccRCC datasets and verified by clinical samples as well as RCC cell lines. Overexpression of CRHBP suppressed cell proliferation, migration, invasion as well as apoptosis in vitro and in vivo. Moreover, the results of western blot analysis showed the effects of CRHBP via upregulating NF-κB and p53-mediated mitochondria apoptotic pathway. Our results suggested that CRHBP may be an effective target to treat ccRCC patients.

scholarly journals Induction of Cell Death in Renal Cell Carcinoma With Combination of D-Fraction and Vitamin C

2013 ◽  
Vol 12 (5) ◽  
pp. 442-448 ◽  
Author(s):  
Bobby Alexander ◽  
Andrew I. Fishman ◽  
Majid Eshghi ◽  
Muhammad Choudhury ◽  
Sensuke Konno
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Death ◽  
Vitamin C ◽  
Cell Carcinoma ◽  
Renal Cell

scholarly journals CircAGAP1 promotes tumor progression by sponging miR-15-5p in clear cell renal cell carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Qi Lv ◽  
Gangmin Wang ◽  
Yinan Zhang ◽  
Aijun Shen ◽  
Junjun Tang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Cell Renal Cell Carcinoma

Abstract Background Accumulating evidence has revealed that circular RNAs (circRNAs), as novel noncoding RNAs, play critical roles in carcinogenesis and tumor progression. However, the functions and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) are largely unknown. Methods The expression and functions of circAGAP1 were identified in clinical samples, ccRCC cells and in vivo animal models. The molecular mechanism of circAGAP1 was investigated by fluorescence in situ hybridization, RNA immunoprecipitation and luciferase assays. Results circAGAP1 (circ0058792) expression was significantly upregulated in ccRCC tissues compared to adjacent nontumor tissues. Moreover, the expression of circAGAP1 was closely related to the tumor size, nuclear grade and clinical stage of ccRCC in patients. Mechanistic studies demonstrated that cytoplasmic circAGAP1 targeted miR-15-5p in an RNA-induced silencing complex. Additionally, miR-15-5p expression was downregulated in ccRCC. Luciferase reporter assays showed that E2F transcription factor 3 (E2F3) was a target of miR-15-5p, and upregulated E2F3 expression was positively correlated with circAGAP1 in ccRCC. Furthermore, the tumor-promoting functions of circAGAP1 could be alleviated by miR-15-5p mimics in vitro and in vivo. Conclusion Our results clarify that circAGAP1 exerts its oncogenic functions as a competitive endogenous RNA (ceRNA) by sponging miR-15-5p, which promotes E2F3 expression. Targeting circAGAP1 might be a new attractive therapeutic strategy in ccRCC.

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