Electrochemotherapy in Primary and Metastatic Skin Tumors

Rodrı́guez-Cuevas, Sergio; Barroso-Bravo, Sinuhé; Almanza-Estrada, Javier; Cristóbal-Martı́nez, Lourdes; González-Rodrı́guez, Enrique

doi:10.1016/s0188-4409(01)00278-8

Cited by 99 publications

(74 citation statements)

References 17 publications

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“…36,37 In addition, as oral squamous cell carcinomas frequently occur on the lips, tongue, gingiva, palate, tonsils and buccal mucosa, that type of injection is convenient. In the present study, we found that BLM (20 mg) treatment with sonoporation in the presence of Optison significantly inhibited tumor growth, as compared with the control groups ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Local delivery system of cytotoxic agents to tumors by focused sonoporation

Iwanaga¹,

Tominaga²,

Yamamoto³

et al. 2007

Cancer Gene Ther

124

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Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporationinduced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Local delivery system of cytotoxic agents to tumors by focused sonoporation

Iwanaga¹,

Tominaga²,

Yamamoto³

et al. 2007

Cancer Gene Ther

124

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“…Indeed, (a) external electric fields generate changes in the transmembrane voltage and, under appropriate conditions, provoke the transient and reversible permeabilisation of the cells, in vitro as well as in vivo and (b) BLM molecules do not diffuse through the plasma membrane and they enter only at the time of the cell electropermeabilisation, in amounts proportional to the external concentration at the moment of EP. Moreover, permeabilising EP can be applied locally in vivo on tumour nodules: the huge increase in the antitumour effectiveness of BLM achieved by the increase in BLM uptake is the basis of electrochemotherapy (ECT), a new way to treat solid tumours that is already under clinical evaluation (Domenge et al, 1996;Mir et al, 1998;Gehl and Geertsen, 2000;Rodriguez-Cuevas et al, 2001;Rols et al, 2002). Therefore, it seemed possible to study in vivo the cell death pathway caused by different amounts of DSB using these experimental conditions.…”

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confidence: 99%

In vivo evolution of tumour cells after the generation of double-strand DNA breaks

et al. 2003

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In vitro, the ratio of single-to double-strand DNA breaks (DSB) and their absolute values determine the cell death pathway. The consequences of the generation of various numbers of DSB generated in vivo in tumour cells have been analysed in two different experimental tumour models. Synchronisation of DSB generation and control of their number have been achieved using different doses of bleomycin (BLM) and tumour cell permeabilisation by means of locally delivered electric pulses. According to BLM dose, different cell death pathways are observed. At a low therapeutic dose, a mitotic cell death pathway is detected. It is characterised by the appearance of 'atypical mitosis', TUNEL and caspase-3 positive, 24 h after the treatment, and later by the presence of typical apoptotic figures, mainly TUNEL positive but caspase-3 negative. Caspase-3 is thus an early marker of apoptosis. Mitotic cell death is also followed by lymphocytic infiltration reaction. At high doses of BLM, pseudoapoptosis is detected within a few minutes after the treatment. These cell death pathways are discussed as a function of the number of DSB generated, by comparison with previous results obtained in vitro using BLM or ionising radiation.

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“…The chemotherapy for recurrent or metastatic tumors results in poor response rates due to the MDR and/or the relative impermeability of cell membranes to chemotherapeutics. Combined treatment consisting of pulsed electric fields and chemotherapeutic agents has been used recently as electrochemotherapy 38,39 . This treatment procedure relies on the physical effects of locally applied electric fields to destabilise cell membranes in the presence of chemotherapeutics.…”

Section: Combination Treatments and Need For Maths And Physicsmentioning

confidence: 99%