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

Abstract

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.

Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy

“…It has been shown that ECT induces a recruitment of mononuclear leucocytes within and around the treated metastatic lesions [17]. While the nature of these infiltrate in mice has been unravelled [18], in humans it has not been investigated.…”

Alternative site of implantation affects tumor malignancy and metastatic potential in mice: Its comparison to the flank model

“…B16F0 melanoma is poorly or non-immunogenic and recidivates after removal. 21,22 MC-C tumor, on the other hand, has the characteristics of a non-infiltrating slow growing fibrosarcoma. 7,23 It is highly immunogenic and, unlike B16F0 melanoma, it never recidivates after removal.…”

Preclinical Validation of Electrochemotherapy as an Effective Treatment for Brain Tumors

“…As described in this article, intratumoral injections of bleomycin were carried out in our study. This regimen tends to give a high number of molecules internalized, leading to necrosis of both tumor tissue and normal tissue (47). From clinical studies, we know that normal tissue may be spared whereas efficient tumor cell kill is obtained with i.v.…”