Changes in metabolic profile, iron and ferritin levels during the treatment of metastatic renal cancer – A new potential biomarker?

Golčić, Marin; Petković, Marija

doi:10.1016/j.mehy.2016.07.015

Cited by 5 publications

(6 citation statements)

References 16 publications

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“…This can be reinforced by the facts that targeted drugs on rcc, including tyrosine kinase (sorafenib and pazopanib) or mammalian target of rapamycin (mTor) inhibitor (everolimus and temsirolimus), inhibit growth factors that have been revealed to promote the growth and spread of tumors (30). The tyrosine kinase, sorafenib, is also known as an inhibitor for cysteine transporter (20), and the mTor pathway is one of the regulators of iron homeostasis via iron, ferritin, and Tfrc (24,28,31). However, recent molecular data (32) insists that caki-2 is a type of papillary rcc rather than a clear cell rcc, which may account for the different responses in this experiment.…”

Section: Discussionmentioning

confidence: 99%

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism

2019

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The microbiome has recently attracted research interest in a variety of subjects, including cancer. in the present study, it was determined that reinforced clostridium media (rcM) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of rcM were investigated for all ingredients of rcM, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (caki-1 and caki-2) and normal human proximal tubular cells (HK-2). as a result, yeast extract exhibited dose-dependent antitumor effects on caki-1 and caki-2, but only slight effects on HK-2. in addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of caki-1 and caki-2. Yeast extract produced cell cycle arrest with an increased G 0 /G 1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin d1. although yeast extract treatment increased anti-oxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. in addition, decreased GPX4 may be related to iron-dependent cell death, particularly in caki-2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism

2019

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“…[6][7][8] The chelation of iron by deferoxamine rescues the experimental ferroptosis, 9 but inhibition of cysteine uptake or the inactivation of GPX4 induces ferroptosis. 6,8 In this context, changes in iron profiles, such as serum iron, ferritin, and transferrin receptor (TfRC), have been suggested as successful chemotherapeutic markers for metastatic RCC, 10 and a variety of iron metabolism genes have been shown to be significantly associated with the survival. 11 The resistance of RCC might be associated with the characteristics of cancer stem cells (CSCs).…”

Section: Introductionmentioning

confidence: 99%

SNU-333 Cells as an Appropriate Cell Line for the Orthotopic Renal Cell Carcinoma Model

Chang

Ohn

Moon

et al. 2021

Technol Cancer Res Treat

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Objective: To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Methods: Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Results: Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial–mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. Conclusion: SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.

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“…Intriguingly, one of the momentous regulators of iron metabolism is the mTOR pathway, which mostly finetunes the rate of iron importation required from the needs of cells. As a result, everolimus, a mTOR inhibitor can increase the levels of TTP and iron with decrease TFR1 levels (54). Hence, the aberrance of gene balancing iron metabolism will lessen the role of mTOR inhibitor and consequently lead to treatment failure.…”

Section: Discussionmentioning

confidence: 99%

The Landscape of Iron Metabolism-Related and Methylated Genes in the Prognosis Prediction of Clear Cell Renal Cell Carcinoma

Mou

Zhang

et al. 2020

Front. Oncol.

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Background: Clear cell renal cell carcinoma (ccRCC) is characteristics of resistance to chemotherapy and radiotherapy. The prognosis of ccRCC was dismay with immense diversity. Iron metabolism disturbance is a common phenomenon in ccRCC. The purpose of our study is to identify and validate the candidate prognostic gene signature of iron metabolism and methylation closely related to the poor prognosis of ccRCC through comprehensive bioinformatics analysis in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Methods: The prognostic iron metabolism-related genes were screened according to the overlapping differentially expressed genes (DEGs) from the TCGA database. We built a prognostic model using risk score method to predict OS, each ccRCC patient's risk score was calculated, and the resulting score can divide these patients into two categories according to the cut-point risk score. The prognostic significance of the hub genes was further evaluated with the Kaplan-Meier (KM) survival and Receiver Operating Characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis was implemented to evaluate the impact of each variable on OS. Furthermore, the prediction power of the 25 gene signatures has been validated using an independent ccRCC cohort from the GEO database. The Gene Set Enrichment Analysis (GSEA) identified the characteristics of hub related oncogenes. Finally, we utilize Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the co-expression network based on these DEGs. Results: In this study, we identified and validated 25 iron metabolism-related and methylated genes as the prognostic signatures, which differentiated ccRCC patients into high and low risk subgroups. The KM analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 25 gene signatures could largely predict OS and DFS for 1, 3, and 5 years in patients with ccRCC. Mou et al. Iron Metabolism Gene Predicts Prognosis in ccRCC Conclusions: Taken together, we identified the key iron metabolism-related and methylated genes for ccRCC through a comprehensive bioinformatics analysis. This study provides a reliable and robust gene signature for the prognostic predictor of ccRCC patients and maybe provides a promising treatment strategy for this lethal disease.

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Changes in metabolic profile, iron and ferritin levels during the treatment of metastatic renal cancer – A new potential biomarker?

Cited by 5 publications

References 16 publications

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism

SNU-333 Cells as an Appropriate Cell Line for the Orthotopic Renal Cell Carcinoma Model

The Landscape of Iron Metabolism-Related and Methylated Genes in the Prognosis Prediction of Clear Cell Renal Cell Carcinoma

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