Mesenchymal stem cells expressing cytosine deaminase inhibit growth of murine melanoma B16F10 in vivo

Krasikova, L. S.; Karshieva, Saida Sh; Cheglakov, I. B.; Belyavsky, A. V.

doi:10.1134/s0026893315060126

Cited by 8 publications

(10 citation statements)

References 23 publications

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“…Melanoma 5-FC Marked inhibition of tumor growth with direct intratumoral transplantation of MSCs expressing CD followed by systemic injection of 5-FC in melanoma mice models (Krasikova et al, 2015) Osteosarcoma 5-FC Inhibition of the tumor growth in mice subcutaneously injected with osteosarcoma Cal72 cells following administration of stable CD/5-FC MSC cell line (NguyenThai et al, 2015) Lewis lung carcinoma 5-FC Significant inhibition of tumor growth with direct intratumoral transplantation of AT-MSCs expressing CD followed by systemic injection of 5-FC in mice models resulted in prolonged survival of treated mice (Krassikova et al, 2016 (Zischek et al, 2009) Lung melanoma metastasis GCV Significant reduction in tumor colonization resulted in amelioration in the survival of murine melanoma lung metastasis models following injection of MSCs expressing TK with GCV (Zhang et al, 2015) AT-MSCs, adipose tissue-derived mesenchymal stem/stromal cells; GCV, ganciclovir, CD, cytosine deaminase, 5-FC, 5-fluorocytosine; TK, thymidine kinase; CTLs, cytotoxic T lymphocytes; iPSCs, induced pluripotent stem cells.…”

Section: Cancer Prodrug Main Resultsmentioning

confidence: 99%

RETRACTED: Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy

Hassanzadeh

Altajer²,

Rahman

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.

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Section: Cancer Prodrug Main Resultsmentioning

confidence: 99%

RETRACTED: Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy

Hassanzadeh

Altajer²,

Rahman

et al. 2021

Front. Cell Dev. Biol.

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“…There are various kinds of studies using different strategies and animal models to test the efficacy of engineered MSCs for the treatment of cancer/metastasis. In some studies, engineered MSCs were delivered after the tumors or metastatic lesions were established in animal models (Chen et al, 2008;Ren et al, 2008;Xin et al, 2009;Gao et al, 2010;Bak et al, 2011;Conrad et al, 2011;Zhang et al, 2011;Wang et al, 2012;Kim et al, 2013;Lee et al, 2013;Martinez-Quintanilla et al, 2013;Yan et al, 2013;Abrate et al, 2014;Altaner et al, 2014;Hu et al, 2014;Harati et al, 2015;Krasikova et al, 2015, Krassikova et al, 2016Lakota et al, 2015;Matuskova et al, 2015;Nouri et al, 2015;Chung et al, 2016;Yan et al, 2017;Yao et al, 2017;Mirzaei et al, 2018;Schug et al, 2018;Segaliny et al, 2019;Suryaprakash et al, 2019). In other studies, tumor cells and engineered MSCs were injected simultaneously in animal models (Fritz et al, 2008;Sasportas et al, 2009;You et al, 2009;Cavarretta et al, 2010;Seo et al, 2011;Altanerova et al, 2012;Fei et al, 2012;Zolochevska et al, 2012;Ahn et al, 2013;Kucerova et al, 2014;…”

Section: Resultsmentioning

confidence: 99%

“…To tackle these problems, genetically modified MSCs carrying suicide genes have been employed to convert non-toxic pro-drugs into active agents for selective elimination of cancer cells. Various genes encoding these "suicide proteins" were used: cytosine deaminase (CD) or cytosine deaminase-uracil phosphoribosyltransferase (CD-UPRT), which converts the pro-drug 5-fluorocytosine (5-FC) into an active agent 5-fluorouracil (5-FU) (Kucerova et al, 2007(Kucerova et al, , 2014You et al, 2009;Cavarretta et al, 2010;Conrad et al, 2011;Altanerova et al, 2012;Fei et al, 2012;Kosaka et al, 2012;Abrate et al, 2014;Krasikova et al, 2015, Krassikova et al, 2016Lakota et al, 2015;Matuskova et al, 2015;NguyenThai et al, 2015;Chung et al, 2016;Toro et al, 2016;Segaliny et al, 2019); herpes simplex virus thymidilate kinase (HSV-TK) (Bak et al, 2011;Martinez-Quintanilla et al, 2013;Nouri et al, 2015) or SV40-TK (Lee et al, 2013), which phosphorylates gancyclovir (GCV) into a toxic substance; and cytochrome P450 reductase (CYP), which converts cyclophosphamide (CPA) into cytotoxic metabolites (Amara et al, 2016).…”

Section: Mscs As Suicide Gene Carriers That Activate Non-toxic Pro-drugs Into Toxic Substancesmentioning

confidence: 99%

“…The combination of AT-MSC-CD/5-FC treatment with SU11274, an inhibitor of the c-Met/hepatocyte growth factor signaling pathway, could provide a complete cure in 9 out of 10 animals at 60 days after EGFP-A375/Rel3 cell injection (Kucerova et al, 2014). Augmentation of CD with herpes virus 1 (HSV-1) tegument protein VP22 in a CD-UPRT fusion construct could also enhance the therapeutic effects of the MSC-CD-UPRT combination (Krasikova et al, 2015). Consistent with studies using animal models, human BM-MSC-CD could migrate to the subcutaneous human gastric cancer MKN45 cells and induce tumor regression in the presence of 5-FC (You et al, 2009).…”

Section: Mscs As Suicide Gene Carriers That Activate Non-toxic Pro-drugs Into Toxic Substancesmentioning

confidence: 99%

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Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Pawitan

Bui

Mubarok

et al. 2020

Front. Cell Dev. Biol.

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Background: The therapeutic capacity of mesenchymal stem cells (also known as mesenchymal stromal cells/MSCs) depends on their ability to respond to the need of the damaged tissue by secreting beneficial paracrine factors. MSCs can be genetically engineered to express certain beneficial factors. The aim of this systematic review is to compile and analyze published scientific literatures that report the use of engineered MSCs for the treatment of various diseases/conditions, to discuss the mechanisms of action, and to assess the efficacy of engineered MSC treatment. Methods:We retrieved all published studies in PubMed/MEDLINE and Cochrane Library on July 27, 2019, without time restriction using the following keywords: "engineered MSC" and "therapy" or "manipulated MSC" and "therapy." In addition, relevant articles that were found during full text search were added. We identified 85 articles that were reviewed in this paper.Results: Of the 85 articles reviewed, 51 studies reported the use of engineered MSCs to treat tumor/cancer/malignancy/metastasis, whereas the other 34 studies tested engineered MSCs in treating non-tumor conditions. Most of the studies reported the use of MSCs in animal models, with only one study reporting a trial in human subjects. Thirty nine studies showed that the expression of beneficial paracrine factors would significantly enhance the therapeutic effects of the MSCs, whereas thirty three studies showed moderate effects, and one study in humans reported no effect. The mechanisms of action for MSC-based cancer treatment include the expression of "suicide genes," induction of tumor cell apoptosis, and delivery of cytokines to induce an immune response against cancer cells. In the context of the treatment of non-cancerous

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“…Its incidence has continuously increased throughout the world for the past 40 years, and the ratio of tumors at the middle and advanced stages, as well as operation infeasibility, has also increased. [1][2][3][4][5][6] Radiotherapy is an important local therapy that plays an important role in the treatment of malignant tumors. However, clinical studies indicate that malignant melanoma resists to conventional rays, and conventional radiotherapy is restricted in the clinical applications of malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell

Qin

Zhang

et al. 2017

Exp Biol Med (Maywood)

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Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate.In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation.This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion ( 12 C 6þ ), in order to accurately determine the clinical efficacy of heavy ion therapy.Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future. AbstractThis study aims to investigate the influence of high linear energy transfer (LET) heavy ion ( 12 C 6þ ) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion ( 12 C 6þ ) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion (

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Mesenchymal stem cells expressing cytosine deaminase inhibit growth of murine melanoma B16F10 in vivo

Cited by 8 publications

References 23 publications

RETRACTED: Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy

RETRACTED: Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell

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