In vivo effects of cavitation alone or in combination with chemotherapy in a peritoneal carcinomatosis in the rat

Abstract

Summary Cavitation (volume oscillations and collapse of gas bubbles), as generated by a co-administration of shockwaves (SW) and microbubbles (SWB) Group, 1984;Calabresi & Chabner, 1990;Valeriote & Santelli, 1984) and only surgery is able to improve survival in less than 10% of the patients with liver metastasis (Nakamura et al., 1992;Registry of Hepatic Metastases, 1988). New therapeutic instruments are thus clearly needed to improve the prognosis of metastasis from bowel malignancies. Despite disappointing results from radiotherapy and conventional hyperthermia, physical methods may be interesting as an alternative approach to, or in combination with, chemotherapy. Biological effects of acoustic waves, like high intensity ultrasound and shock waves have been studied for many years (Flynn, 1964;Church & Miller, 1983); while direct cytotoxic effects may play a minor role, several studies have shown that damage is caused to microvessels and endothelial cells, causing vascular disruption as well as the production of free radicals, leading to hypoxia and indirect toxicity to the affected tissue (Miller, 1987). It has also been demonstrated that the cytotoxicity of shock waves was obtained mostly through acoustic cavitation, which is the transitory volume oscillations of gas microbubbles induced by rapidly varying pressure waves, eventually resulting in the collapse of bubbles (Dear et al., 1988). When a bubble collapses near an interface with a cell membrane, such dramatic damage is inflicted to the cell as to induce cell death (Delius et al., 1989;Miller, 1987;Miller et al., 1991). However, the therapeutic potentialities of cavitation have so far remained confined to in vitro experimental studies and have not evolved toward clinical applications for two reasons: (1) ultrasound was not able to induce cytotoxicity unless generated in vitro in specific experimental conditions (Church & Miller, 1983); (2) (Prat et al., 199 la). Further experiments with HT-29 cells in suspension and viable rat colon peritoneal metastases treated in vitro showed that cavitation could hinder cell proliferation and induce complete tissue necrosis (Prat et al., 1991b). In a more recent study (Prat et al., personal communication), the cytotoxicity of FUra to HT-29 cells was greatly enhanced by a preliminary exposure of the cells to cavitation, through potentially synergistic mechanisms.In the present study, we aimed at investigating the relevance of cavitation to the treatment of a disseminated digestive tumour in vivo. Materials and methodsCells DHD K12 PROb cells (a gift from Pr Martin, INSERM U252, Dijon, France) originated from a dimethyl-hydrazineinduced rat colon carcinoma were cultured in Dulbecco's modified Eagle's medium supplemented with 8% fetal calf serum under 8% CO2. The cells were cultured to confluence in 75 cm2 flasks and detached after 12 days of culture by 2.5/1000 trypsin/0.2/1000 EDTA. Cell viability was assessed before each use by trypan blue exclusion; it was always over 90%. AnimalsMale and female BD IX rats, syng...

Ultrasound mediated delivery of drugs and genes to solid tumors

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Theranostic Applications of Nanomaterials in Cancer: Drug Delivery, Image-Guided Therapy, and Multifunctional Platforms

“…Xu et al developed PLGA-nanobubble contrast agents encapsulating Texas Red dye that could be used for dual-mode optical and ultrasound imaging [174]. High intensity frequency ultrasound can also be used in thermal ablation and hyperthermia interventions, and several reports have demonstrated a synergistic effect of these approaches with chemotherapy [175, 176]. …”

Focused liver ablation by cavitation in the rabbit: a potential new method of extracorporeal treatment.

“…This important point can be considered in several ways: firstly, microvascular damage results in ischaemia and fibrosis; it can thus be expected that cells in the focal area continue to die after shockwave is given, and that tumour growth rate would seriously be affected, as has already been shown in vitro29 and in vivo. 30 Secondly, the repetition of treatment sessions will probably complete and reinforce therapeutic effects. Thirdly, cavitation, as a local treatment, should probably be part of combined therapeutic schedules including chemotherapy or immunomodulators for instance.…”