Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas

Heller, Loree C.; Todorović, Vesna; Čemažar, Maja

doi:10.1038/cgt.2013.71

Cited by 25 publications

(28 citation statements)

References 50 publications

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“…The destruction of tube formation was also observed in the group of GET of SCR plasmid. Similar results were previously obtained in our [ 11 ] and other studies [ 60 , 61 ], indicating that plasmid backbone alone, thus devoid of therapeutic genes, can affect biological properties of the cells in vitro and in vivo . Our results in vivo provide encouraging evidence that endoglin is indeed important for angiogenesis and its silencing is effectively preventing it.…”

Section: Discussionsupporting

confidence: 92%

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects

et al. 2015

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Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

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Section: Discussionsupporting

confidence: 92%

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects

et al. 2015

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“…GET of the control plasmid pControl also resulted in significant tumor growth delay, by 5.6 ± 0.6 days in B16F1 and 7.0 ± 1.4 days in B16F10 tumors. This was already observed in previous studies that electrotransfer of DNA can induce regression of B16 tumors, as tumor regression was observed after delivery of single-stranded or double-stranded DNA in both immunocompetent and immunodeficient mice under different pulsing protocols [ 28 , 29 ].…”

Section: Resultssupporting

confidence: 65%

Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105) shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects

Dolinšek

Serša

Prosen

et al. 2015

Cancers

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Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively). The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells.

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“…Since then several clinical trials using electrochemotherapy have been performed for treatment of small tumors, such as cutaneous and subcutaneous metastases [7][8][9][10]14,64,65], for larger tumors such as chest wall breast cancer recurrences [11,66], as well as for treatment of tumors in internal organs and deep seated tumors [67][68][69][70][71]. Electroporation is also investigated for use in gene electrotransfer where it can be used for DNA vaccine [72] and treatment of cancers [73,74]. Thus, electroporation is a well-established clinical method and can easily be tested in combination with new or other drugs.…”

Section: Electroporationmentioning

confidence: 99%

A Comprehensive Review of Calcium Electroporation—A Novel Cancer Treatment Modality

Frandsen

Vissing

Gehl

2020

Cancers

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Calcium electroporation is a potential novel anti-cancer treatment where high calcium concentrations are introduced into cells by electroporation, a method where short, high voltage pulses induce transient permeabilisation of the plasma membrane allowing passage of molecules into the cytosol. Calcium is a tightly regulated, ubiquitous second messenger involved in many cellular processes including cell death. Electroporation increases calcium uptake leading to acute and severe ATP depletion associated with cancer cell death. This comprehensive review describes published data about calcium electroporation applied in vitro, in vivo, and clinically from the first publication in 2012. Calcium electroporation has been shown to be a safe and efficient anti-cancer treatment in clinical studies with cutaneous metastases and recurrent head and neck cancer. Normal cells have been shown to be less affected by calcium electroporation than cancer cells and this difference might be partly induced by differences in membrane repair, expression of calcium transporters, and cellular structural changes. Interestingly, both clinical data and preclinical studies have indicated a systemic immune response induced by calcium electroporation. New cancer treatments are needed, and calcium electroporation represents an inexpensive and efficient treatment with few side effects, that could potentially be used worldwide and for different tumor types.

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Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas

Cited by 25 publications

References 50 publications

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects

Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105) shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects

A Comprehensive Review of Calcium Electroporation—A Novel Cancer Treatment Modality

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