Protein profiling of microdomains purified from renal cell carcinoma and normal kidney tissue samples

2012 ◽  
Vol 8 (4) ◽  
pp. 1007-1016 ◽  
Author(s):  
F. Raimondo ◽  
L. Morosi ◽  
C. Chinello ◽  
R. Perego ◽  
C. Bianchi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kidney Tissue ◽  
Protein Profiling ◽  
Normal Kidney ◽  
Tissue Samples ◽  
Normal Kidney Tissue

scholarly journals LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Quan Hong ◽  
Shuqiang Wang ◽  
Shuxin Liu ◽  
Xiangmei Chen ◽  
Guangyan Cai
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kidney Tissue ◽  
The Cancer Genome Atlas ◽  
Gene Methylation ◽  
Cell Renal Cell Carcinoma ◽  
Tissue Samples ◽  
Downstream Signaling ◽  
Cancer Genome Atlas

Clear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. It is an urgent mission to find more therapeutic targets for advanced ccRCC. Leucine-rich a-2-glycoprotein 1 (LRG1) is a secreted protein associated with a variety of malignancies. Our study focused on the expression and mechanism of LRG1 in ccRCC based on data from The Cancer Genome Atlas (TCGA) and provided primary verification including LRG1 expression detection, LRG1 gene methylation detection, and downstream signaling detection. We found that LRG1 was overexpressed in ccRCC kidney tissue samples, and the methylation level of LRG1 gene was significantly decreased in ccRCC. Moreover, the expression of LRG1 was negatively related to patient survival. Based on our previous study and the verification reported in this article, we propose that demethylation-induced overexpression of LRG1 is likely to accelerate ccRCC progression via the TGF-β pathway.

scholarly journals Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248983
Author(s):  
Christudas Morais ◽  
Retnagowri Rajandram ◽  
Jade S. Blakeney ◽  
Abishek Iyer ◽  
Jacky Y. Suen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Normal Kidney ◽  
Intracellular Calcium Mobilization ◽  
Protease Activated Receptor 2 ◽  
Calcium Mobilization Assay

Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.

scholarly journals The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2574
Author(s):  
Jee Soo Park ◽  
Myung Eun Lee ◽  
Won Sik Jang ◽  
Koon Ho Rha ◽  
Seung Hwan Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Parp Inhibitor ◽  
Renal Tumors ◽  
Low Grade ◽  
Normal Kidney ◽  
The Dead ◽  
The Impact

Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

scholarly journals Differential protein profiling of renal cell carcinoma urinary exosomes

2013 ◽  
Vol 9 (6) ◽  
pp. 1220 ◽  
Author(s):  
F. Raimondo ◽  
L. Morosi ◽  
S. Corbetta ◽  
C. Chinello ◽  
P. Brambilla ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Protein Profiling ◽  
Differential Protein ◽  
Urinary Exosomes

scholarly journals Detection of urinary miRNAs for diagnosis of clear cell renal cell carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giovanni Cochetti ◽  
Luigi Cari ◽  
Giuseppe Nocentini ◽  
Vincenza Maulà ◽  
Chiara Suvieri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Kidney Tissue ◽  
Internal Controls ◽  
Cell Renal Cell Carcinoma ◽  
Set Up ◽  
Tissue Specimens ◽  
Data Banks

AbstractThe lack of symptoms at the early stages of clear cell renal cell carcinoma (ccRCC) allows the tumour to metastasize, leading to a dramatic reduction in patient survival. Therefore, we studied and set up a method based on urinary microRNAs (miRNAs) for the diagnosis of ccRCC. First, miRNA expression in ccRCC specimens and kidney tissues from healthy subjects (HSs) was investigated through analysis of data banks and validated by comparing expression of miRNAs in ccRCC and adjacent non-cancerous kidney tissue specimens by RT-qPCR. Subsequently, we developed an algorithm to establish which miRNAs are more likely to be found in the urine of ccRCC patients that indicated miR-122, miR-1271, and miR-15b as potential interesting markers. The evaluation of their levels and three internal controls in the urine of 13 patients and 14 HSs resulted in the development of a score (7p-urinary score) to evaluate the presence of ccRCC in patients. The resulting area under the Receiver Operating Characteristic (ROC) curve, sensitivity, and specificity were equal to 0.96, 100% (95% CI 75–100%), and 86% (95% CI 57–98%), respectively. In conclusion, our study provides a proof of concept that combining the expression values of some urinary miRNAs might be useful in the diagnosis of ccRCC.

Enhanced orotate phosphoribosyltransferase activity in renal cell carcinoma and its prognostic significance

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15590-15590
Author(s):  
Y. Mizutani ◽  
D. Toiyama ◽  
T. Shiraishi ◽  
T. Nakamura ◽  
K. Mikami ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
De Novo ◽  
Prognostic Significance ◽  
Normal Kidney ◽  
Orotate Phosphoribosyltransferase ◽  
Synthetic Process ◽  
Dna And Rna ◽  
Fresh Frozen

15590 Background: 5-Fluorouracil ( 5-FU ) is an anticancer agent clinically used against various cancers including renal cell carcinoma ( RCC ). 5-FU is a prodrug and orotate phosphoribosyltransferase ( OPRT ) is the principal enzyme which directly converts 5-FU to an active anticancer metabolite, 5-fluoro-2’-deoxyuridine 5’-monophosphate. Furthermore, OPRT is the key enzyme in the de novo DNA and RNA synthetic process, which converts orotic acid to orotidine 5’-phosphate. Little is known about the significance of OPRT in a variety of cancers including RCC. We investigated OPRT activity in 83 RCC and evaluated the association between OPRT activity and the stage/grade of RCC. The relationship between OPRT activity in RCC cells and their sensitivity to 5-FU was also examined. Methods: OPRT activity in non-fixed fresh frozen RCC and normal kidney were determined enzymatically by the 5-FU phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. Results: OPRT activity was approximately 8.5-fold higher in RCC compared to normal kidney. OPRT activity in T3/4 RCC was 3-fold higher than that in T1/2 RCC. OPRT activity in M1 RCC was 2.5-fold higher than that in M0 RCC. In addition, OPRT activity in Stage III/IV RCC was 3-fold higher than that in Stage I/II RCC. The level of OPRT activity in Grade 3 RCC was 3-fold higher than that in Grade 1/2 cancer. Patients with RCC with low OPRT activity had a longer postoperative disease-specific survival than those with high activity in the 5-year follow-up. OPRT activity in RCC cells positively correlated with their sensitivity to 5-FU. Conclusions: The present study has demonstrated that OPRT activity in RCC was higher than that in normal kidney, and that OPRT activity positively correlated with the stage/grade of RCC. Moreover, higher OPRT activity in RCC predicted worse prognosis and higher sensitivity to 5-FU. These results suggest that OPRT activity may be used as both a prognostic parameter and a predictive indicator for 5-FU efficacy in RCC. No significant financial relationships to disclose.

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