scholarly journals Tim-3ScFv-Transforming Lactobacillus Inhibits Transplanted Tumour of Renal Cell Carcinoma

2021 ◽  
Author(s):  
Zerong Chen ◽  
Haibo Zhang ◽  
Jialiang Hui ◽  
Yaodong Jiang ◽  
Zehai Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Lactococcus Lactis ◽  
Renal Cell ◽  
Volume Growth ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Promoting Effect ◽  
Spleen Lymphocytes

Abstract Background T cell immunoglobulin-3(Tim-3) is an immune checkpoint molecule; Tim-3 antibody is suitable for treating malignant renal tumours. However, Tim-3 antibody drugs are expensive, which limits their application. To overcome the disadvantages of expensive immunotherapeutic drugs, Lactococcus lactis was used as the host bacteria to express Tim-3 single-chain antibody in the intestine, and its promotion of the mouse immune system and inhibitory effects on the transplanted tumour of kidney cancer in mice were tested. Methods Molecular cloning technology was used to construct plasmids pLAN-CTB-Tim3scFv and pLAN-Tim3scFv, which were transformed into Lactococcus lactis. The expression of the transformed bacteria was analysed using western blotting, and the immune activity of secreted proteins of the transformed bacteria was detected using ELISA in vitro. A subcutaneous transplanted tumour model of renal adenocarcinoma was constructed in RAG mice, and the promoting effect of transforming bacteria on the activation of mouse spleen lymphocytes, and its inhibitory effect on transplanted tumours in mice was analysed. Results (1) Transformed Lactococcus lactis NZ -CTB-Tim3scFv and NZ -Tim3scFv, which secrete CTB-Tim3scFv and Tim3scFv single-chain antibodies, were successfully constructed. (2) CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv transformed bacteria showed immunological activity. (3) Compared with the NZ-Tim3scFv and NZ-Vector groups, the characteristics of the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. The tumour volume of the NZ-CTB-Tim3scFv group increased the least, and was statistically different from that of the other two groups. Conclusions The Tim-3 single-chain antibody gene was successfully constructed and transformed in Lactococcus lactis. After feeding mice NZ-CTB-Tim3scFv transforming Lactobacillus, the CTB-Tim3scFv secreted by the transforming Lactobacillus promoted the proliferation and activation of spleen lymphocytes and inhibited volume growth, cell proliferation, and angiogenesis of the tumour in mice. In summary, apply transgenic lactobacillus secreting CTB-Tim-3scFv, to perform its role in anti-tumor immunotherapy through oral approach, is low cost and convenient. It is expected to become a new way of immunotherapy for renal cell carcinoma.

scholarly journals Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Quoc Thang Pham ◽  
Daiki Taniyama ◽  
Yohei Sekino ◽  
Shintaro Akabane ◽  
Takashi Babasaki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
In Silico Analysis ◽  
Immunohistochemical Analysis ◽  
Rna Seq ◽  
Anoikis Resistance ◽  
Silico Analysis ◽  
Proliferation And Invasion

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words)

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

scholarly journals Neuropilin 1 and Neuropilin 2 gene invalidation or pharmacological inhibition reveals their relevance for the treatment of metastatic renal cell carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Aurore Dumond ◽  
Etienne Brachet ◽  
Jérôme Durivault ◽  
Valérie Vial ◽  
Anna K. Puszko ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Metabolism ◽  
Boyden Chamber ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma ◽  
Immunodeficient Mice ◽  
And Migration

Abstract Background Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway. Methods We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs. Results Knock-out of the NRP1 and NRP2 genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients. Conclusions Our study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.

Malignant phenotype of renal cell carcinoma cells is switched by Ukrain administration in vitro

2011 ◽  
Vol 22 (8) ◽  
pp. 749-762 ◽  
Author(s):  
Nicoletta Gagliano ◽  
Letizia Pettinari ◽  
Massimo Aureli ◽  
Carla Martinelli ◽  
Elena Colombo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Carcinoma Cells ◽  
Malignant Phenotype

scholarly journals COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells in vitro

2016 ◽  
Vol 14 (2) ◽  
pp. 1371-1378 ◽  
Author(s):  
La Ta ◽  
Chengrui Xuan ◽  
Nianzeng Xing ◽  
Xiaojun Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell

scholarly journals MicroRNA-373 promotes tumorigenesis of renal cell carcinoma in vitro and in vivo

2017 ◽  
Vol 16 (5) ◽  
pp. 7048-7055 ◽  
Author(s):  
Yanli Li ◽  
Da Zhang ◽  
Jiaxiang Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell

Pro-apoptotic effects of Amblyomin-X in murine renal cell carcinoma “in vitro”

2012 ◽  
Vol 66 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Erica Mie Akagi ◽  
Paulo Luiz de Sá Júnior ◽  
Simone Michaela Simons ◽  
Maria Helena Bellini ◽  
Sandra Alves Barreto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Apoptotic Effects

scholarly journals Role of SIRT2 in Regulation of Stemness of Cancer Stem-Like Cells in Renal Cell Carcinoma

2018 ◽  
Vol 49 (6) ◽  
pp. 2348-2357 ◽  
Author(s):  
Ruojing Wei ◽  
Dalin He ◽  
Xinshi Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cancer Metastasis ◽  
Fluorescent Protein ◽  
Luciferase Reporter ◽  
Tumor Sphere ◽  
Bivariate Correlation ◽  
Induced Apoptosis

Background/Aims: Cancer stem cells (CSCs) contribute to tumorgenesis, invasion and metastasis, and are typically resistant to chemotherapy. Recent reports showed that SIRT2 was upregulated in several cancers. However, whether SIRT2 may be a CSC marker in renal cell carcinoma (RCC) is not clear. Methods: The SIRT2 levels in both RCC samples and the corresponding normal kidney samples (NT) were assessed by RT-qPCR and ELISA. The association between SIRT2 levels and patient survival was examined using Bivariate correlation analysis by Spearman’s Rank Correlation Coefficients. The survival of the patients was analyzed using Kaplan-Meier curve. In vitro, 2 RCC cell lines were co-transduced with a lentivirus expressing both a green fluorescent protein and a luciferase reporter under a cytomegalovirus promoter, and another lentivirus expressing a nuclear red fluorescent protein reporter under the control of a SIRT2 promoter for differentiating SIRT2+ vs SIRT2- RCC cells by flow cytometry. The SIRT2+ vs SIRT2- RCC cells were examined for the potential of forming tumor sphere in a tumor sphere formation assay, resistance to fluorouracil-induced apoptosis by CCK-8 assay, and the frequency of forming tumor in vivo after serial adoptive transplantation by bioluminescence. Results: The levels of SIRT2 were higher in RCC samples than NT. The prognosis of RCC patients with high SIRT2 was worse than that of with low SIRT2. Compared to SIRT2- cells, SIRT2+ cells formed more tumor spheres, appeared to be more resistant towards fluorouracil-induced apoptosis, and generated bigger tumors with higher frequency after serial adoptive transplantation. Conclusion: SIRT2 may be highly expressed in the RCC stem-like cells and regulates cancer metastasis. Selective knockout of SIRT2 or elimination of SIRT2+ cells may improve the therapeutic outcome for patients with RCC.

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