PhiC31/PiggyBac modified stromal stem cells: effect of interferon γ and/or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on murine melanoma

Bahrambeigi, Vahid; Ahmadi, Nafiseh; Moisyadi, Stefan; Urschitz, Johann; Salehi, Roya; Javanmard, Shaghayegh Haghjooy

doi:10.1186/1476-4598-13-255

Cited by 18 publications

(14 citation statements)

References 50 publications

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“…Currently, inhibition of tumor growth is the primary and most fundamental facet in the progression of cancer treatment ( 29 ). Enhancement of apoptosis in tumor tissues has been reported to contribute to inhibition of tumor growth and may lead to immunological recognition of immune system in cancer patients ( 30 ). Conventional radiotherapy is the most frequently used treatment of NPC, however, radiotherapy injury seriously may damage the immune system ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Combined effects of Lenvatinib and iodine‑131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress

Wang

Zhuang

et al. 2018

Exp Ther Med

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Nasopharyngeal carcinoma (NPC) is a type of malignant tumor characterized by high invasiveness, metastatic potential and worldwide incidence among patients with head and neck cancer. It has previously been demonstrated that Lenvatinib (LEB) is an efficient anti-cancer agent by multi-targeting of tyrosine kinase inhibitors. Iodine-131 (I-131) therapy has been accepted for the treatment of thyroid cancer and other carcinomas. In the present study, the combined effects of LEB and I-131 were investigated on NPC and the potential signal pathway mediated by LEB and I-131 on NPC cells was explored. Inhibitory effects of LEB and I-131 for NPC cells growth were investigated via MTT assay. Migration and invasion of NPC cells was studied by aggression assays following incubation of LEB and I-131. Apoptosis of NPC cells and tissues were analyzed via flow cytometry and TUNEL assay, respectively. Apoptosis-related gene expression levels in NPC cells following treatment with LEB and I-131 were determined by western blotting. Endoplasmic reticulum (ER) stress in NPC cells were analyzed in NPC cells and tumor tissues. Immunohistochemistry was used to analyze the efficacy of LEB and I-131 in NPC-tumor bearing mice. The results demonstrated that combined treatment of LEB and I-131 significantly inhibited growth, apoptosis, migration and invasion of NPC cells compared with single agent therapy. Apoptosis-related gene expression levels of caspase-3 and caspase-9 were upregulated by LEB and I-131, whereas B call lymphoma-2, and P53 were downregulated in NPC cells and tumor tissues. In addition, signal mechanism analysis demonstrated that combined treatment of LEB and I-131 promoted expression levels of activating transcription factor 6, inositol-requiring protein 1 (IER1), protein kinase RNA-like endoplasmic reticulum kinase (RERK), and C/EBP homologous protein in NPC cells. Furthermore, combined treatment of LEB and I-131 markedly inhibited in vivo growth of NPC and further prolonged survival of experimental mice compared with single agent and control groups. Immunohistochemistry indicated that c-jun N-terminal kinase and Caspase-3 were increased in NPS tumor tissues in xenograft models treated with LEB and I-131. Apoptotic bodies were also increased in tumors treated by LEB and I-131. In conclusion, these findings indicate that combined treatment of LEB and I-131 may inhibit NPC growth and aggression through upregulation of ER stress, suggesting combined treatment of LEB and I-131 may be a potential therapeutic schedule for the treatment of NPC.

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Section: Discussionmentioning

confidence: 99%

Combined effects of Lenvatinib and iodine‑131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress

Wang

Zhuang

et al. 2018

Exp Ther Med

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“…In most contexts, IFNγ exerts an antiproliferative effect on melanoma cells 100,101,110,111,[123][124][125][126] by inducing G1 cell cycle arrest through mechanisms related to the regulation of p27 Kip1 (also known as CDKN1B), CDK6, cyclin A, cyclin E and miR-29 family members [127][128][129] . IFNγ-induced cell cycle arrest has long been known to be associated with increased invasiveness of melanoma cells.…”

Section: Cell-autonomous Functions In Melanomamentioning

confidence: 99%

Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways

2019

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Targeted therapy and immunotherapy have greatly improved the prognosis of patients with metastatic melanoma, but resistance to these therapeutic modalities limits the percentage of patients with long-lasting responses. Accumulating evidence indicates that a persisting subpopulation of melanoma cells contributes to resistance to targeted therapy or immunotherapy, even in patients who initially have a therapeutic response; however, the root mechanism of resistance remains elusive. To address this problem, we propose a new model, in which dynamic fluctuations of protein expression at the single-cell level and longitudinal reshaping of the cellular state at the cell-population level explain the whole process of therapeutic resistance development. Conceptually, we focused on two different pivotal signalling pathways (mediated by microphthalmia-associated transcription factor (MITF) and IFNγ) to construct the evolving trajectories of melanoma and described each of the cell states. Accordingly, the development of

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“…45, [99][100][101][102][103] In particular, successful transgene transposition in MSCs was demonstrated using SB100X technology, which resulted in up to 10-fold higher transposition efficiency compared to the SB11 system. The genetically engineered MSCs maintained the ability to undergo osteogenic, myogenic, and adipogenic differentiation after electroporation with the SB100X or PB transposon system.…”

Section: Hscmentioning

confidence: 96%

“…45 Recently, adipose-derived MSCs secreting interferon gamma were generated using the hyPBase system as a basis for cancer immunotherapy in murine models. 103 MABs are capable of penetrating blood vessels during intra-arterial delivery, in contrast to myoblasts, which can only be delivered directly in the muscle tissue itself. MABs can undergo myogenic differentiation to promote muscle regeneration in dystrophic animal models.…”

Section: Hscmentioning

confidence: 99%

Transposons: Moving Forward from Preclinical Studies to Clinical Trials

Tipanee¹,

VandenDriessche

Chuah

2017

Human Gene Therapy

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Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein. Stable transposition efficiency can be substantially increased by using "next-generation" transposon systems that combine codon-usage optimization with hyper-activating mutations in the SB or PB transposases. By virtue of their relatively large capacity, gene therapy applications with relatively large therapeutic transgenes, such as full-length dystrophin, can now be envisaged. The authors and others have shown that efficient and stable gene transfer can be achieved with these next-generation transposons in several clinically relevant primary cells, such as CD34 hematopoietic stem/progenitor cells, T cells, and mesenchymal and myogenic stem/progenitor cells that are amenable for ex vivo transfection. Alternatively, in vivo transposon gene delivery has been explored using non-viral vectors or nanoparticles or in combination with viral vectors. The therapeutic potential of these SB- and PB-based transposons has been demonstrated in preclinical models that mimic the cognate human diseases. However, there are still challenges impeding clinical translation of transposons pertaining mainly to the typical limiting efficiencies of most non-viral transfection methods and the intrinsic DNA toxicity. Nevertheless, it is particularly encouraging that transposons have now been used in gene therapy clinical trials. In particular, transposon-engineered T cells expressing chimeric antigen receptors are starting to yield promising results in patients with hematological malignancies.

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PhiC31/PiggyBac modified stromal stem cells: effect of interferon γ and/or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on murine melanoma

Cited by 18 publications

References 50 publications

Combined effects of Lenvatinib and iodine‑131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress

Combined effects of Lenvatinib and iodine‑131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress

Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways

Transposons: Moving Forward from Preclinical Studies to Clinical Trials

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