scholarly journals Gender differences in components of insulin-like signaling pathway in kidney tissues in local and advanced clear cell renal cell carcinoma

2019 ◽  
Vol 10 (1) ◽  
pp. 35-41
Author(s):  
Oleg I. Kit ◽  
Elena M. Franciyants ◽  
Aleksey N. Shevchenko ◽  
Anna A. Breus ◽  
Irina V. Neskubina ◽  
...  
Keyword(s):  
Gender Differences ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Kidney Cancer ◽  
Advanced Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Tissues

Objective:study of components of an insulin-like signaling pathway in kidney tissues in local and advanced clear cell renal cell carcinoma depending on the gender of patients.Materials and methods:the object of the study was conditionally intact kidney tissue and tumor and perifocal tissues obtained during the surgical treatment of 100 patients with histologically confirmed clear cell kidney cancer (local cancer (Т1-2N0М0) n=50, advanced cancer (Т3-4N0М1) n=50). Levels of the IGF-1, IGF-2, IGFBP-1 and IGFBP-2 growth factors (Mediagnost, Germany) and STH-releasing (Peninsula Laboratories International, USA) were determined by ELISA using standard test systems. The results were analyzed using Statistica 6.0 (Stat-Soft, 2001).Results:levels of IGFВР-2 and STH-releasing in conditionally intact tissues in women were 44% and 40% lower than in men, respectively. The IGFВР-2 level in perifocal tissues of women was 38% higher than in men, while STH-releasing was lower by 1.9 times. Tumor tissues of local kidney cancer in women showed significant decrease in IGF-1 by 25%, IGFВР-1 by 29% and IGFВР-2 by 2 times. Levels of IGFBP-1 and IGFBP-2 in conditionally intact tissues of women with advanced cancer were 2 and 2.7 times lower, respectively, compared to men. IGFBP-2 and STH-releasing in perifocal tissues of women were increased by 43.8% and 44.6%, respectively. In tumor tissues of women with advanced kidney cancer, levels of IGF-1 were 1.7 times higher, IGF-2 – 31% lower, IGFBP-2 – 2.8 times lower and STH-releasing – 36% lower, compared to men.Conclusions:IGFBP-2 in all studied kidney tissues in local and advanced cancer was an identically variable index characterizing gender differences in the body’s reaction to the tumor process.

scholarly journals ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglin Gao ◽  
Lei Gao ◽  
Simin Wang ◽  
Xiaokai Shi ◽  
Chuang Yue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Invasion Assay ◽  
Cell Renal Cell Carcinoma ◽  
Atf3 Expression

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence has shown that ATF3 is associated with tumor progression.MethodsUsing qPCR, the expression of ATF3 was detected in 93 patients with ccRCC, including 24 paired normal and tumor tissues, which were used to further compare ATF3 expression through western blotting and immunohistochemistry. Lentivirus was used for the overexpression or knockdown of ATF3, and the consequent alteration in function was analyzed through CCK8 assay, colony formation assay, wound healing assay, invasion assay, and flow cytometry. The potential mechanism affected by ATF3 was analyzed through gene set enrichment analysis (GSEA) and verified using western blotting, invasion assay, or immunofluorescence staining. Furthermore, a xenograft mouse model was used to assess the function of ATF3 in vivo.ResultsATF3 expression was significantly decreased in ccRCC compared to that in adjacent normal tissues. Through gain- and loss-of-function experiments performed in an in vitro assay, we found that ATF3 could regulate ccRCC cell proliferation, cycle progression, migration, and invasion. In the in vivo study, the xenograft mouse model revealed that ATF3 overexpression can inhibit the growth of ccRCC. Moreover, the mechanism analysis showed that suppression of ATF3 could lead to an increase the expression of β-catenin and promote β-catenin transfer to the nucleus, and might be affected by EGFR/AKT/GSK3β signaling.ConclusionATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategies for ccRCC include targeting the ATF3/EGFR/AKT/GSK3β/β−catenin signaling pathway.

Tumor-infiltrating regulatory T lymphocytes orchestrate oncogenic PAK1-conferred immune evasion in clear-cell renal cell carcinoma

2019 ◽  
Author(s):  
Yang Qu ◽  
Jiajun Wang ◽  
Qi Bai ◽  
Yangyang Qi ◽  
Yifan Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
T Lymphocytes ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Regulatory T Lymphocytes ◽  
Tumor Tissues ◽  
Pak1 Expression

Abstract Background: Little is known about the associations between PAK1 and anti-tumor immunity in clear-cell renal cell carcinoma (ccRCC). This study aims to explore the prognostic value of PAK1 in ccRCC patients and investigated the molecular immune mechanism for its oncogenic role. Methods: We retrospectively enrolled 282 ccRCC patients undergoing nephrectomy between 2005 and 2007 in Zhongshan hospital. Immunohistochemistry evaluated PAK1, CCL22, FOXP3 and CD8 expression in clinical specimens. Fresh tumor tissues, para-tumor tissues and peripheral blood samples for RT-PCR, ELISA, flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. We compared clinical outcomes by Kaplan-Meier survival analysis and Cox regression model. Bioinformatics analysis performed in TCGA KIRC cohort. Results: High PAK1 expression indicated poorer overall survival (OS) and recurrence free survival (RFS) (both p<0.001) in ccRCC patients. Multivariate analyses indicated PAK1 as an independent prognostic factor. In clinical samples, PAK1 clearly correlated with immunosuppressive microenvironment in ccRCC tissues. Significantly, PAK1 positively correlated with Tumor-infiltrating regulatory T lymphocytes (Tregs). Furthermore, IL-10+ and TGF-β+ tumor-infiltrating Tregs both increased in PAK1 high tumors. Additionally, CCL22 was highly secreted in PAK1 high tumors. After treated by IPA-3 (an PAK1 inhibitor), CCL22 secretion was clearly inhibited (p<0.001). Finally, we built a nomogram to predict overall survival for ccRCC patients with higher predictive accuracy. Conclusions: Increased PAK1 expression predicted dismal prognosis in ccRCC patients by inducing tumor immune escape. IL-10+ and TGF-β+ tumor-infiltrating Tregs recruited by CCL22 play dominant immunosuppressive roles in PAK1 high tumors.

scholarly journals The Uniqueness of Clear Cell Renal Cell Carcinoma: Summary of the Process and Abnormality of Glucose Metabolism and Lipid Metabolism in ccRCC

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaochen Qi ◽  
Quanlin Li ◽  
Xiangyu Che ◽  
Qifei Wang ◽  
Guangzhen Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Cancer Metabolism ◽  
Clear Cell ◽  
Future Research ◽  
Cell Renal Cell Carcinoma

Kidney cancer is a cancer with an increasing incidence in recent years. Clear cell renal cell carcinoma (ccRCC) accounts for up to 80% of all kidney cancers. The understanding of the pathogenesis, tumor progression, and metastasis of renal carcinoma is not yet perfect. Kidney cancer has some characteristics that distinguish it from other cancers, and the metabolic aspect is the most obvious. The specificity of glucose and lipid metabolism in kidney cancer cells has also led to its being studied as a metabolic disease. As the most common type of kidney cancer, ccRCC has many characteristics that represent the specificity of kidney cancer. There are features that we are very concerned about, including the presence of lipid droplets in cells and the obesity paradox. These two points are closely related to glucose metabolism and lipid metabolism. Therefore, we hope to explore whether metabolic changes affect the occurrence and development of kidney cancer by looking for evidence of changes on expression at the genomic and protein levels in glucose metabolism and lipid metabolism in ccRCC. We begin with the representative phenomenon of abnormal cancer metabolism: the Warburg effect, through the collection of popular metabolic pathways and related genes in the last decade, as well as some research hotspots, including the role of ferroptosis and glutamine in cancer, systematically elaborated the factors affecting the incidence and metastasis of kidney cancer. This review also identifies the similarities and differences between kidney cancer and other cancers in order to lay a theoretical foundation and provide a valid hypothesis for future research.

scholarly journals Identification of alterations in the nucleotide sequence of the chromatin remodeling gene PBRM1 in clear cell renal cell carcinoma patients

2018 ◽  
Vol 22 (7) ◽  
pp. 873-877
Author(s):  
E. A. Klimentova ◽  
I. R. Gilyazova ◽  
A. A. Izmailov ◽  
I. M. Sultanov ◽  
M. A. Bermisheva ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Nucleotide Sequence ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Chromatin Remodeling ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
The Third

Kidney cancer is a heterogeneous group of malignant tumors, the vast majority of which are renal cell carcinomas (RCC) of various morphological types, of which the most common is the clear cell renal cell carcinoma (ccRCC). Particular attention in the carcinogenesis of the ccRCC is given to a number of tumor suppressor genes located on the short arm of the third chromosome. One of these genes, which are inactivated in the case of ccRCC is the PBRM1 gene encoding the PBAF SWI/SNF subunit of the chromatin remodeling complex, BAF180. The PBRM1 gene is located on the short arm of the third chromosome in the 3p21 region near the von Hippel-Lindau gene (VHL), the mutation in which is the main event in the occurrence of ccRCC. The aim of our investigation is identification of changes in the nucleotide sequence of the PBRM1 tumor suppressor gene in patients with ccRCC. 210 pairs of DNA samples isolated from ccRCC tissue were studied. Analysis of changes in the nucleotide sequence of DNA was carried out by HRM analysis and direct sequencing. In the PBRM1 gene, two somatic mutations were found (c.233G>A (p.D45N) in exon 2, c.1675-1676delTC in exon 15) which were not described previously, and one known polymorphic variant rs17264436 (in exon 23). The frequency of detected mutations was 0.95 % of cases. Analysis of the allelic association for the polymorphic locus rs17264436 showed a statistically significant increase in the risk of developing advanced kidney cancer in carriers of allele rs17264436*A, which can be used in the development of prognostic marker panels. Perhaps the low frequency of mutations in the samples we studied is due to the fact that the inactivation of the PBRM1 gene takes place in other ways, and may also be due to the ethno-specificity of the studied group of patients.

Pathological significance of C3aR signaling in the tumor cells of clear cell renal cell carcinoma: a clinical observation

2020 ◽  
Author(s):  
Jing-Min Zheng ◽  
Xiong Tian ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Tumor Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Ki 67 ◽  
Tumor Tissues

Abstract Background Increasing evidences suggest that anaphylotoxin-induced signaling is involved in tumor pathogenesis, but the exact role of C3a/C3aR signaling in clear cell renal cell carcinoma (ccRCC) still remains to be investigated. The aim of the study was to investigate the pathological significance of C3a/C3aR signaling in ccRCC. Methods The expression of C3aR and C3 mRNA in the tumor tissues of ccRCC patients were analyzed by using the data from TCGA database. The expression of C3aR and C3c protein in the tumor tissues of another 129 ccRCC patients were examined by immunohistochemistry. Results Compared with the normal controls, both C3aR and C3 mRNA increased in the tumor tissues. Patients with higher C3 mRNA had shorter survival time. Immunostaining for C3aR and C3c also increased in the tumor tissues when compared with the adjacent normal renal tissues. Higher level of C3aR in the tumor cells and C3c in the tumor tissues were found to be associated with indices reflecting poor prognosis including higher tumor grade, the presence of necrosis in tumor tissues and shorter survival time. Besides, the level of C3aR in the tumor cells and C3c in the tumor tissues were found to correlate with the level of Vimentin, E-Cadherin and the ratio of Ki-67 positive tumor cells. Conclusions These results support the idea that C3aR signaling is over-activated in the tumor cells and may contribute to the progression of ccRCC. Inducing EMT and promoting the proliferation of tumor cells might be among the mechanisms underlying the role of C3aR signaling in ccRCC.

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