Delivery of sFIT-1 engineered MSCs in combination with a continuous low-dose doxorubicin treatment prevents growth of liver cancer

Niu, Jian; Wang, Yue; Wang, Ji; Bin, Liu; Hu, Xin

doi:10.18632/aging.101146

Cited by 6 publications

(3 citation statements)

References 34 publications

(33 reference statements)

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“…Additionally, sFlt1 is thought to be a natural antagonist of VEGF . Recent studies have found that sFlt1 has an antitumor effect on several cancer cells ( 48 – 50 ). Enhanced sFlt1 expression in the serum of breast cancer patients inhibits circulating tumor cells entering the peripheral blood, which may contribute to favorable outcomes ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

et al. 2018

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The present study aimed to identify new key genes as potential biomarkers for the diagnosis, prognosis or targeted therapy of clear cell renal cell carcinoma (ccRCC). Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus. GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples. The Database for Annotation, Visualization and Integrated Discovery was utilized for functional and pathway enrichment analysis. STRING v10.5 and Molecular Complex Detection were used for protein-protein interaction (PPI) network construction and module analysis, respectively. Regulation network analyses were performed with the WebGestal tool. UALCAN web-portal was used for expression validation and survival analysis of hub genes in ccRCC patients from The Cancer Genome Atlas (TCGA). A total of 65 up- and 164 downregulated genes were identified as DEGs. DEGs were enriched with functional terms and pathways compactly related to ccRCC pathogenesis. Seventeen hub genes and one significant module were filtered out and selected from the PPI network. The differential expression of hub genes was verified in TCGA patients. Kaplan-Meier plot showed that high mRNA expression of enolase 2 (ENO2) was associated with short overall survival in ccRCC patients (P=0.023). High mRNA expression of cyclin D1 (CCND1) (P<0.001), fms related tyrosine kinase 1 (FLT1) (P=0.004), plasminogen (PLG) (P<0.001) and von Willebrand factor (VWF) (P=0.008) appeared to serve as favorable factors in survival. These findings indicate that the DEGs may be key genes in ccRCC pathogenesis and five genes, including ENO2, CCND1, PLT1, PLG and VWF, may serve as potential prognostic biomarkers in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

et al. 2018

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“…Several studies have shown that engineered‐MSCs could migrate to the tumor and metastatic sites and deliver the anticancer agents including IFN‐α, IFN‐ß, CX3CL1, IL‐2, IL‐12, NK4, sFIT‐1, and suicide gene 22,29,37,38 . Recently, various investigations have focused on TRAIL as one of the most promising anticancer factors.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo

Salmasi

Hashemi

Mahdipour

et al. 2020

Biotechnol Progress

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Cell-based delivery system is a promising strategy to protect therapeutic agents from the immune system and provide targeted delivery. Mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in cell-based gene therapy due to their unique features including tumor-tropic property and migratory ability. However, gene transfer into MSCs is limited due to low efficiency and cytotoxicity of carriers. In this study, we designed a novel delivery system based on polyethylenimine (PEI 25) to improve these features of carrier and transfect plasmid encoding TRAIL to MSCs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand of TNF family with selective effect on cancerous cells. Then, death induction and migration ability of TRAIL-expressing MSCs was studied in melanoma cells. The effect of engineered-MSCs as an antitumor vehicle was also investigated in mice bearing melanoma cells. Our findings indicated that heterocyclic amine derivative of PEI 25 showed significant improvement in MSCs viability determined by MTT assay and gene expression using fluorescent microscopy, flow cytometry, and Western blot analysis. We observed that engineered-MSCs could migrate toward and induce cell death in B16F0 cells in vitro. The single administration of TRAIL-expressing MSCs could delay tumor appearance and efficiently reduce tumor weights. Hematoxylin and eosin staining of tumor sections revealed extensive neoplastic cells necrosis. Furthermore, engineered-MSCs could migrate and localize to tumors sites within 5 days. Our results indicated that MSCs engineered by modified-PEI/TRAIL complexes could be considered as a promising cellular vehicle for targeted tumor suppression.

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“…Importantly, the effectiveness and safety of this combination therapy are verified through in vivo experiments. 31,32 MiR-199a-3p, the third most highly expressed miRNA in the normal liver, is down-regulated in almost all HCC cells and associated with poor prognosis. And mTOR has been identified as the direct target of miR-199a-3p.…”

Section: Mscs and Adriamycinmentioning

confidence: 99%

The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma

Zhang

Zhu

et al. 2022

Cancer Medicine

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Primary liver cancer is the seventh most common cancer and the second most common cause of cancer death in the world. 1 Globally, hepatocellular carcinoma (HCC) is the main histological type of liver cancer, accounting for more than 75% of the total number of liver cancers. 2 Liver cancer stem cells (LCSCs), recognized by certain surface markers, are responsible for the tumorigenesis, recurrence, metastasis, chemotherapy resistance and poor prognosis of HCC. 3 Increasing evidence supports the great effects of the tumor microenvironment (TME) on the generation, development and metastasis of HCC. TME is composed of diversified cells and non-cellular components. 4 Mesenchymal stem cells (MSCs), an integral part of TME, are considered to be a key factor in tumor progression and metastasis. MSCs are also referred to as "mesenchymal stromal cells", which can further be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and other cells in vitro. 5 Recently, massive research has been devoted to exploring the association between HCC and MSCs. The function of

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Delivery of sFIT-1 engineered MSCs in combination with a continuous low-dose doxorubicin treatment prevents growth of liver cancer

Cited by 6 publications

References 34 publications

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo

The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma

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