xenotransplantation model
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2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Wan ◽  
Juan Zhou ◽  
Lu Fu ◽  
Yubin Li ◽  
Huawu Zeng ◽  
...  

Experimental and clinical evidence has indicated that the natural product ascorbic acid (AA) is effective in preventing and treating various types of cancers. However, the effect of AA on liver cancer metastasis has not yet been reported. Cancer stem cells (CSCs) play pivotal roles in cancer metastasis. Here, we demonstrated that AA selectively inhibited the viability of both liver cancer cells and CSCs, reduced the formation of cancer cell colonies and CSC spheres, and inhibited tumor growth in vivo. Additionally, AA prevented liver cancer metastasis in a xenotransplantation model without suppressing stemness gene expression in liver CSCs. Further study indicated that AA increased the concentration of H2O2 and induced apoptosis in liver CSCs. Catalase attenuated the inhibitory effects of AA on liver CSC viability. In conclusion, AA inhibited the viability of liver CSCs and the growth and metastasis of liver cancer cells in vitro and in vivo by increasing the production of H2O2 and inducing apoptosis. Our findings provide evidence that AA exerts its anti-liver cancer efficacy in vitro and in vivo, in a manner that is independent of stemness gene regulation.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Tong-tong Li ◽  
Jie Mou ◽  
Yao-jie Pan ◽  
Fu-chun Huo ◽  
Wen-qi Du ◽  
...  

Abstract Background Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. Methods In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. Results We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3′-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of β-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. Conclusions PAK5 contributed to the sorafenib resistant characteristics of HCC via β-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.


2021 ◽  
Vol 22 (3) ◽  
pp. 1099
Author(s):  
Si-Yen Liu ◽  
Sheng-Nan Lo ◽  
Wan-Chi Lee ◽  
Wei-Chuan Hsu ◽  
Te-Wei Lee ◽  
...  

Nanotargeted liposomes may be modified with targeting peptide on the surface of a prepared liposome to endow specificity and elevate targeting efficiency. The aim of this study was to develop a radioactive targeted nanoparticle, the 111In-cyclic RGDfK-liposome, and its advantage of recognizing the αVβ3 integrin was examined. The cyclic RGDfK modified liposomes were demonstrated the ability to bind the αVβ3 integrin expressed on the surface of human melanoma cell in vitro and in vivo. The effects of the cyclic RGDfK-liposome on the functioning of phagocytes was also examined, showing no considerable negative effects on the engulfment of bacteria and the generation of reactive oxygen species. Based upon these findings, the cyclic RGDfK- liposome is said to be a promising agent for tumor imaging.


2021 ◽  
Vol 30 ◽  
pp. 096368972110545
Author(s):  
Yunhan Ma ◽  
Baiyi Xie ◽  
Junjun Guo ◽  
Yingyu Chen ◽  
Mengya Zhong ◽  
...  

Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB/c allogeneic hearts were transplanted into C57BL/6 mice, and survived 31 days after LEF treatment. Compared to normal saline treatment, LEF treatment decreased xenoreactive T cells and CD19+ B cells in recipient splenocytes. Most importantly, LEF treatment protected myocardial cells by decreasing xenoreactive T and B cell infiltration, inflammatory gene expression, and IgM deposition in grafts. In vivo assays revealed that LEF treatment eliminated xenoreactive and alloreactive T and B lymphocytes by suppressing the activation of the NF-κB signaling pathway. Taken together, these observations complement the evidence supporting the potential use of LEF in xenotransplantation.


Author(s):  
Susana Pascoal ◽  
Sarah Grissenberger ◽  
Eva Scheuringer ◽  
Rita Fior ◽  
Miguel Godinho Ferreira ◽  
...  

2020 ◽  
Vol 12 (12) ◽  
pp. 1431-1437
Author(s):  
Hui Liu ◽  
Peng Zhang ◽  
Fang Zhang ◽  
Qing Liu

A drug delivery system based on nanomaterials has demonstrated a powerful function in disease treatment. In this study, a titanium-dioxide-nanotube-based cisplatin (nano-TiO2-DDP) delivery system was designed, and its effects in rats with nasopharyngeal carcinoma (NPC) and on tumor cells were analyzed. First, we obtained electrochemistry anodic oxidation (EAO) for the preparation of Nnano-TiO2, which was adopted as the carrier of cisplatin (CDDP). Then, we used a scanning electron microscope (SEM) to characterize and study the surface morphology of nano-TiO2. At the cellular level, flow cytometry, MTT, and Transwell assays were performed to analyze the apoptosis, proliferation, and invasion of cells treated by nano-TiO2-DDP, respectively. At the animal level, a xenotransplantation model was established for evaluating tumor growth and changes in experimental animals after injection of nano-TiO2-DDP. As a result, nano-TiO2-DDP strongly suppressed the invasion and vitality of tumor cells, induced their apoptosis, and delivered DDP more efficiently than did systems without a nano-TiO2 structure. In addition, injected nano-TiO2-DDP strongly inhibited the growth of solid tumors in vivo. Therefore, we believe that nano-TiO2-DDP can effectively suppress the growth of NPC, and it is more efficient than conventional drugs.


Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2449
Author(s):  
Miwako Nishio ◽  
Kumiko Saeki

Brown adipose tissue (BAT), which is a thermogenic fat tissue originally discovered in small hibernating mammals, is believed to exert anti-obesity effects in humans. Although evidence has been accumulating to show the importance of BAT in metabolism regulation, there are a number of unanswered questions. In this review, we show the remaining mysteries about BATs. The distribution of BAT can be visualized by nuclear medicine examinations; however, the precise localization of human BAT is not yet completely understood. For example, studies of 18F-fluorodeoxyglucose PET/CT scans have shown that interscapular BAT (iBAT), the largest BAT in mice, exists only in the neonatal period or in early infancy in humans. However, an old anatomical study illustrated the presence of iBAT in adult humans, suggesting that there is a discrepancy between anatomical findings and imaging data. It is also known that BAT secretes various metabolism-improving factors, which are collectively called as BATokines. With small exceptions, however, their main producers are not BAT per se, raising the possibility that there are still more BATokines to be discovered. Although BAT is conceived as a favorable tissue from the standpoint of obesity prevention, it is also involved in the development of unhealthy conditions such as cancer cachexia. In addition, a correlation between browning of mammary gland and progression of breast cancers was shown in a xenotransplantation model. Therefore, the optimal condition should be carefully determined when BAT is considered as a measure the prevention of obesity and improvement of metabolism. Solving BAT mysteries will open a new door for health promotion via advanced understanding of metabolism regulation system.


Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Monica Anne Wall ◽  
Vasantha Padmanabhan ◽  
Ariella Shikanov

Abstract Ovarian tissue cryopreservation and banking provides a fertility preservation option for patients who cannot undergo oocyte retrieval; it is quickly becoming a critical component of assisted reproductive technology programs across the world. While the transplantation of cryopreserved ovarian tissue has resulted in over 130 live births, the field has ample room for technological improvements. Specifically, the functional timeline of grafted tissue and each patient’s probability of achieving pregnancy is largely unpredictable due to patient-to-patient variability in ovarian reserve, lack of a reliable method for quantifying follicle numbers within tissue fragments, potential risk of reintroduction of cancer cells harbored in ovarian tissues, and an inability to control follicle activation rates. This review focuses on one of the most common physiological techniques used to study human ovarian tissue transplantation, xenotransplantation of human ovarian tissue to mice and endeavors to inform future studies by discussing the elements of the xenotransplantation model, challenges unique to the use of human ovarian tissue, and novel tissue engineering techniques currently under investigation.


Author(s):  
Yangyang Deng ◽  
Ming Zhou ◽  
Ying Lu ◽  
Jiao Chen ◽  
Zuhui Pu ◽  
...  

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