scholarly journals Regulation of Immunity in Clear Cell Renal Carcinoma: Role of PD-1, PD-L1, and PD-L2

2021 ◽  
Vol 43 (2) ◽  
pp. 1072-1080
Author(s):  
Liudmila Spirina ◽  
Zahar Yurmazov ◽  
Evgeny Usynin ◽  
Irina Kondakova ◽  
Ekaterine Ladutko ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cancer Progression ◽  
Clear Cell ◽  
Mrna Level ◽  
Aggressive Cancer ◽  
New Instrument ◽  
Cell Renal Carcinoma ◽  
Vhl Protein ◽  
Cancer Dissemination ◽  
Mtor Modulation

Regulation of immunity is a unique oncogenic mechanism that differs in different cancers. VHL deficient clear cell renal cell carcinomas (ccRCC) trigger the immune response resulting in cancer progression. This study aimed to investigate PD-1, PD-L1, and PD-L2 expression in ccRCC primary cancers and metastatic tissues associated with the p-VHL content, transcriptional, and growth factors expression. Methods: A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level was performed by PCR in real-time. Western blotting analysis was used for detecting the p-VHL protein content in tissues. Results: The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. Conclusion: We present a new instrument targeting pathologies with p-VHL/HIF altered function that impact the PD-L2 expression through the change in transcriptional, growth factors, and AKT/mTOR modulation.

scholarly journals VHL, BAP1, PBRM1, SETD2 Expression in Clear Cell Renal Carcinoma, Association With PD-1, PD-L1, PD-L2 mRNA Level

2021 ◽  
Author(s):  
Liudmila Spirina ◽  
Zahar Yurnazov ◽  
Evgeny Usynin ◽  
Irina Kondakova ◽  
Ekaterina Ladutko ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Renal Carcinoma ◽  
Mrna Level ◽  
Rna Isolation ◽  
Primary Tumors ◽  
Aggressive Cancer ◽  
New Instrument ◽  
Cell Renal Carcinoma ◽  
Vhl Protein ◽  
Cancer Dissemination

Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

scholarly journals Inverse Correlation of miR-27a-3p and CDH5 Expression Serves as a Diagnostic Biomarker of Proliferation and Metastasis of Clear Cell Renal Carcinoma

2020 ◽  
Author(s):  
Yifang Wang ◽  
Xiaohui Zhou ◽  
Peipei Han ◽  
Yunliang Lu ◽  
Xuemin Zhong ◽  
...  
Keyword(s):  
Clear Cell ◽  
Meta Analysis ◽  
Mrna Level ◽  
Inverse Correlation ◽  
Renal Clear Cell Carcinoma ◽  
Clinicopathological Characteristics ◽  
Diagnostic Biomarker ◽  
Protein Levels ◽  
Normal Tissues ◽  
Cell Renal Carcinoma

Abstract Background: Cadherin-5 (CDH5) is aberrantly expressed in a variety of human cancers and plays an important role in angiogenesis. But its role in renal clear cell carcinoma (ccRCC) remains to be understood. Methods: The dysregulation of CDH5 expression in ccRCC and its association with clinicopathological characteristics were analyzed using the TCGA database. A meta-analysis was performed to verify the alteration of CDH5 expression in ccRCC using the GEO database. Quantitative RT-PCR and immunohistochemical staining were applied to assess the transcriptional and protein levels of CDH5. TargetScan and Tarbase were employed to predict the miRNAs with the potential to target mRNA of CDH5.Results: The mRNA level of CDH5 in ccRCC was significantly higher than in normal tissue. CDH5 mRNA expression could therefore serve as a potential diagnostic biomarker for ccRCC (AUC=0.844). However, the reduced CDH5 transcription levels were significantly correlated with patients in the T3-4 stage, lymph node and distant metastasis, as well as with a worse clinical outcome. We further observed that CDH5, at the protein level, was almost absent in ccRCC samples. In addition, a few databases screen showed that mir-27a-3p, is a highly conserved miRNA targeting CDH5. The expression of mir-27a-3p was significantly elevated in ccRCC tissues in contrast to normal tissues. Importantly, it was positively associated with the T3-4 stage and M stage, respectively, suggesting that the expression level of mir-27a-3p could serve as a diagnostic biomarker for ccRCC (AUC=0.775).Conclusion: Our data suggest that the reduced translational levels of CDH5 in ccRCC was related to the overexpression of mir-27a-3p. The higher mir-27a-3p and lower CDH5 expression significantly correlated with advanced clinical stages for ccRCC patients.

scholarly journals Expression and content of VHL in kidney cancer tissue, relationship with clinical and morphological parameters of the disease, expression of transcriptional and growth factors

2021 ◽  
Vol 67 (5) ◽  
pp. 694-698
Author(s):  
Lyudmila Spirina ◽  
Zahar Yurmazov ◽  
Evgenii Usy`nin ◽  
Irina Kondakova
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Cancer Tissue ◽  
Morphological Parameters ◽  
Vhl Protein ◽  
The Relationship

Introduction. The molecular picture of the development of HIF overexpression against VHL deficiency background is a key event associated with the manifestation and progression of clear cell renal cell carcinoma. However, this indicator's significance for the development of the disease and the formation of a response to targeted therapy is not clear. The study aimed to study the relationship between the expression and content of VHL in kidney cancer tissue with clinical, morphological parameters, mRNA level NF-κB p65, NF-κB p50, HIF-1, HIF-2, VEGF, and CAIX. Material and methods. The study included 39 patients with renal cell carcinoma. The disease's localized form (T1-2N0M0) was diagnosed in 20 patients; 19 patients had a disseminated process (T1-3N0-1M1). The study's material was normal, and tumor tissue was obtained during the surgical stage of treatment. VHL expression was determined by real-time PCR. The pVHL protein content was estimated using the Western Blotting method. Results. As a result of the study, it was noted that an increase in the VHL expression, together with a decrease in its protein level, was associated with an increase in tumor size. The prevalence of the disease was accompanied by an increase in both mRNA and VHL content in cancers. There was a negative correlation between the level of VHL expression, the content of the corresponding protein, and a positive association with the expression of NF-κB p65. VHL content in cancers was associated with decreased expression of NF-κB p50, NF-κB p65, and VEGF. Discussion. An increase in VHL expression in tumor tissue promoted the growth of mRNA of transcription factors, in particular NF-κB, which is accompanied by tumor spread. An increase in the VHL protein content led to the suppression of the mRNA level of transcriptional and growth factors, which is probably associated with their inactivation, including through proteasome cleavage, and is an important stage in oncogenesis. Conclusion. The relationship between the expression and content of the VHL protein is of decisive importance in the development of the disease, the formation of distant metastases.

1651: Molecular Prognostic Modeling Using Protein Expression Profile in Clear Cell Renal Carcinoma

2004 ◽  
Vol 171 (4S) ◽  
pp. 436-436 ◽  
Author(s):  
Hyung L. Kim ◽  
David B. Seligson ◽  
Nicolette Janzen ◽  
Matthew H. Bui ◽  
Robert A. Figlin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Profile ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Clear Cell Renal Carcinoma ◽  
Protein Expression Profile ◽  
Cell Renal Carcinoma ◽  
Prognostic Modeling

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

2011 ◽  
Vol 58 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Seong H Yoo ◽  
Kyoungbun Lee ◽  
Ji Y Chae ◽  
Kyung C Moon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma

Oncogene ◽  
2007 ◽  
Vol 26 (45) ◽  
pp. 6499-6508 ◽  
Author(s):  
J S P Yuen ◽  
M E Cockman ◽  
M Sullivan ◽  
A Protheroe ◽  
G D H Turner ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Clear Cell Renal Carcinoma ◽  
Cell Renal Carcinoma

scholarly journals The Influence of the Extremely Low Frequency Electromagnetic Field on Clear Cell Renal Carcinoma

2021 ◽  
Vol 22 (3) ◽  
pp. 1342
Author(s):  
Aleksandra Cios ◽  
Martyna Ciepielak ◽  
Wanda Stankiewicz ◽  
Łukasz Szymański
Keyword(s):  
Electromagnetic Field ◽  
Cancer Cells ◽  
Cell Lines ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Low Frequency ◽  
Inhibitory Effect ◽  
Hek293 Cells ◽  
Clear Cell Renal Carcinoma ◽  
Cell Renal Carcinoma

The development of new technologies and industry is conducive to the increase in the number and variety of electromagnetic field (EMF) sources in our environment. The main sources of EMF are high-voltage lines, household appliances, audio/video devices, mobile phones, radio stations, and radar devices. In the growing use of electronic devices, scientists are increasingly interested in the effects of EMF on human health. Even though many studies on the effects of EMF have already been carried out, none of them has shown a significant effect on mammals, including humans. Moreover, it is not entirely clear how EMF influences cell behavior. The International Agency for Research on Cancer on 31 May 2011, classified PEM as a possible carcinogenic factor. This study aimed to investigate the effect of the electromagnetic field on morphological and functional changes in clear cell renal carcinoma. The research was carried out on in vitro cultures of four cell lines: HEK293, 786-O 769-P, and Caki1. The results of the research showed that the EMF of low frequency had a slight effect on the viability of cells. EMF, which induced cell arrest in the G1 phase, increased the number of early apoptotic cells and decreased the number of viable cells in the 786-O line. EMF did not affect the proliferation and viability of HEK293 cells. Extreme low-frequency EMF (ELF-EMF) also showed an inhibitory effect on the migration and metastatic properties of clear cell kidney cancer cells. Moreover, shortly after the end of ELF-EMF exposure, significant increases in ROS levels were observed in all tested cell lines. As part of the work, it was shown that low-frequency EMF shows an inhibitory effect on the proliferation of primary cancer cells, diminishing their migratory, invasive, and metastatic abilities. It also increases the apoptosis of cancer cells and the amount of reactive oxygen species. Based on the results of our research, we want to point up that the effect of ELF-EMF depends on a specific metabolic state or at a specific stage in the cell cycle of the cells under study.

A combined postoperative nomogram for survival prediction in clear cell renal carcinoma

2021 ◽  
Author(s):  
Ying Ming ◽  
Xinyi Chen ◽  
Jingxu Xu ◽  
Haiyu Zhan ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Clear Cell ◽  
Survival Prediction ◽  
Clear Cell Renal Carcinoma ◽  
Cell Renal Carcinoma

scholarly journals TNIP1 Inhibits Proliferation And Promotes Apoptosis In Clear Cell Renal Carcinoma Through Targeting C/Ebpβ

2019 ◽  
Vol Volume 12 ◽  
pp. 9861-9871
Author(s):  
Yong Yang ◽  
Jinhai Fan ◽  
Shenglu Han ◽  
Enyuan Li
Keyword(s):  
Renal Carcinoma ◽  
Clear Cell ◽  
Clear Cell Renal Carcinoma ◽  
Cell Renal Carcinoma
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