The Wide Experience of the Sequential Therapy for Patients with Metastatic Renal Cell Carcinoma

Lambea, J.; Anido, Urbano; Etxániz, Olatz; Flores, Luis Esteves; Montesa, A.; Sepúlveda, Juan Manuel; Esteban, Emilio

doi:10.1007/s11912-016-0553-6

Cited by 5 publications

(9 citation statements)

References 88 publications

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“…Numerous studies have examined the role of cancerassociated genes, mRNAs, and proteins in cancer cells, to determine their pathologic characteristics, prognostic value, and potential for use in targeted therapy, although most of them have not yet become clinically routine (3,4). Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity (5).…”

Section: Introductionmentioning

confidence: 99%

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Zhao

Zhang

Duan

et al. 2018

Molecular Cancer Research

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Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of and assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation and tumor growth Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease. TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. .

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Section: Introductionmentioning

confidence: 99%

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Zhao

Zhang

Duan

et al. 2018

Molecular Cancer Research

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“…2 Although there are a number of new therapeutic options for RCC, for example, tyrosine kinase inhibitors and angiogenesis inhibitors, only an unsatisfactory response rate can be achieved so far. 3 Compared with other tumors, there are very few tumor biomarkers for renal cancer. 4 Therefore, novel biomarkers and therapeutic targets are urgently required to guide clinical decisions.…”

Section: Introductionmentioning

confidence: 99%

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495

et al. 2017

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Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinomaassociated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients. KeywordsRenal cell carcinoma, urothelial carcinoma-associated 1, enhancer of zeste homolog 2, miR-495, tumor proliferation Long non-coding RNAs (lncRNAs), that are more than 200 bases in length, consist of exons and introns in structure, without ORFs, and are not highly conserved. Recent reports suggest that lncRNAs play an important role in regulation of diverse cellular processes such as cell growth and apoptosis and cancer metastasis. 5 Several lncRNAs have been reported to be participated in renal cancer, such as, Qiao et al. 6 found that a decrease in lncRNA growth arrest-specific 5 (GAS5) expression was associated with RCC genesis and progression and overexpression of GAS5 can inhibit the RCC progression. A recent study indicated that LncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) could function as a competing endogenous RNA to regulate zinc finger e-box binding homeobox 2 (ZEB2) expression by sponging miR-200s in clear cell kidney carcinoma. 7 HOX transcript antisense RNA (HOTAIR) was overexpressed in RCC, and knockdown of HOTAIR led to the weakening of the recruitment and binding abilities of enhancer of zeste homolog 2 (EZH2) and H3K27me3 locus with lncRNA HOTAIR and inhibited cell prol...

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“…In addition, a previous study has demonstrated that the median survival of patients with metastatic RCC is ~13 months (3). In recent years, various molecular targeting agents have been used in the treatment of patients with advanced RCC (4). The anti-cancer effects of these agents, including prolonged survival, are more effective compared with those of other forms of therapy, such as immunotherapy (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, various molecular targeting agents have been used in the treatment of patients with advanced RCC (4). The anti-cancer effects of these agents, including prolonged survival, are more effective compared with those of other forms of therapy, such as immunotherapy (4,5). However, the effective period of these molecular targeting therapies is short, and the frequency and severity of adverse reactions are relatively high (5).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have examined the role of cancer-associated genes, messenger RNAs and proteins in cancer cells, to determine their pathological characteristics, prognostic value and potential for use in targeted therapy (4,17). In recent years, the surrounding cancer-associated stromal cells have also been implicated in tumor development and progression (18).…”

Section: Introductionmentioning

confidence: 99%

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Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

et al. 2016

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Abstract. Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67-and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm 2 . In addition, CD57 + and CD68 + cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68 + macrophage density, whereas it was positively associated with CD57 + NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7-33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57 + NK cell and CD68 + macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology.

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The Wide Experience of the Sequential Therapy for Patients with Metastatic Renal Cell Carcinoma

Cited by 5 publications

References 88 publications

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

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