Abstract
Current developments in medical technology have focused on therapeutic treatments that selectively and effectively address specific pathological areas, minimizing side effects on healthy tissues. In this regard, many procedures have been developed to provide non-invasive therapy, for example therapeutic ultrasound (US). In the medical field, in particular in cancer research, it has been observed how ultrasounds can cause cell death and inhibit cell proliferation of cancer cells, while preserving healthy ones with almost negligible side effects. Various studies have shown that low intensity pulse ultrasound (LIPUS) and low intensity continuous ultrasound (LICUS) regulate the proliferation, cell differentiation and cavitation phenomena. Nowadays, there are poorly known aspects of low intensity US treatment, in terms of biophysical and biomechanical effects on target cells. The aim of this study is to set up an innovative apparatus for US treatment of pancreatic ductal adenocarcinoma (PDAC) cells, monitoring parameters such as acoustic intensity, acoustic pressure, stimulation frequency and treatment protocol. To this purpose, we have developed a custom-made set up for the US stimulation at 1.2 and 3 MHz of tridimensional (3D) cultures of PDAC cells (PANC-1, Mia Paca-2 and BxPc3 cells). Images of the 3D cultures were acquired, and the Calcein/PI assay was applied to detect US-induced cell death. Overall, the setup we have presented paves the way to an innovative protocol for tumor treatment. The system can be used either alone or in combination with small molecules or recombinant antibodies in order to propose a novel combined therapeutic approach.
Highlights
IntroductionLocal treatments, such as radiation and hyperthermia treatments, are typically used for cancer treatment
Besides systemic chemotherapy, local treatments, such as radiation and hyperthermia treatments, are typically used for cancer treatment
The thermal trends recorded during the stimulation procedure confirm a low intensity treatment; cell death is not caused by thermal effects, but only by the mechanical effects of ultrasound
Summary
Local treatments, such as radiation and hyperthermia treatments, are typically used for cancer treatment. In these methods, the level of cell death induction is used as an indicator of therapeutic effectiveness. Despite a wide range of possible methodological options, there is a lack of valid strategies, based on the effect of high temperatures, but with a valuable effect per se. Ultrasound technology has emerged as a possible novel therapeutic approach, despite the need for proper validation. In the management of solid cancer, the possible application of shock waves is ascribable to the pure mechanical effects on the cells. In addition to traditional surgery and chemotherapy, the use of high intensity focused ultrasound (HIFU) has been established as a noninvasive technique for tumor therapy
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