Development of a Cancer Treatment with the Concomitant Use of Low-Intensity Ultrasound: Entering the Age of Simultaneous Diagnosis and Treatment

Emoto, Makoto

doi:10.3390/diagnostics4020047

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Studies also found that low intensity ultrasound caused chromosomal damage and DNA breaks [ 57 ]. Focused, low intensity ultrasound may also be useful for targeting tumors [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells

et al. 2021

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Background Paclitaxel (Taxol) is a microtubule-stabilizing drug used to treat several solid tumors, including ovarian, breast, non-small cell lung, and pancreatic cancers. The current treatment of ovarian cancer is chemotherapy using paclitaxel in combination with carboplatin as a frontline agent, and paclitaxel is also used in salvage treatment as a second line drug with a dose intensive regimen following recurrence. More recently, a dose dense approach for paclitaxel has been used to treat metastatic breast cancer with success. Paclitaxel binds to beta tubulin with high affinity and stabilizes microtubule bundles. As a consequence of targeting microtubules, paclitaxel kills cancer cells through inhibition of mitosis, causing mitotic catastrophes, and by additional, not yet well defined non-mitotic mechanism(s). Results In exploring methods to modulate activity of paclitaxel in causing cancer cell death, we unexpectedly found that a brief exposure of paclitaxel-treated cells in culture to low intensity ultrasound waves prevented the paclitaxel-induced cytotoxicity and death of the cancer cells. The treatment with ultrasound shock waves was found to transiently disrupt the microtubule cytoskeleton and to eliminate paclitaxel-induced rigid microtubule bundles. When cellular microtubules were labelled with a fluorescent paclitaxel analog, exposure to ultrasound waves led to the disassembly of the labeled microtubules and localization of the signals to perinuclear compartments, which were determined to be lysosomes. Conclusions We suggest that ultrasound disrupts the paclitaxel-induced rigid microtubule cytoskeleton, generating paclitaxel bound fragments that undergo degradation. A new microtubule network forms from tubulins that are not bound by paclitaxel. Hence, ultrasound shock waves are able to abolish paclitaxel impact on microtubules. Thus, our results demonstrate that a brief exposure to low intensity ultrasound can reduce and/or eliminate cytotoxicity associated with paclitaxel treatment of cancer cells in cultures.

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“…Studies also found that low intensity ultrasound caused chromosomal damage and DNA breaks [ 57 ]. Focused, low intensity ultrasound may also be useful for targeting tumors [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells

et al. 2021

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“…It was firstly experimented and investigated by the Makoto with IC50 of low-intensity ultrasound against sarcoma cells. Based on the IC50, only the tumor site received radiation (using Sonitoron 2000: Richmar, USA) for 3 minutes, 3 times a week, under the condition of 1MHZ, 50%-DF and 2.0 w/cm2 in vivo.The results of development of blood vessels around the tumor were then obtained by color Doppler ultrasound imaging and quantified on the basis of prefixed controlled scale [68].…”

Section: Quantificationmentioning

confidence: 99%

Assessment Methods of Angiogenesis and Present Approaches for Its Quantification

Khan¹,

Shakir²,

Khan³

et al. 2014

CRJ

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Angiogenesis is the extension of blood vessels from the prevailing vessels. It is an essential process in the formation and development of blood vessels, so it is supportive in healing of wound while its inhibition may help to restrict the size of tumor. To quantify the effect of an agent on angiogenesis, a standardized preclinical screening assay is necessary. The objective of this review is to document all the methods of angiogenesis assessment and specific techniques to quantify the results, majorly focusing on the modes of calculation and concerns that researchers need to make before reaching to any conclusion. Scientific research on angiogenesis relies on different models for assessment, including in vitro, in vivo and in ovo models. Many of these assays are practiced to test the effect of both pro and anti angiogenic agents. The findings articulated in this study will help to provide better visions into the pathophysiology of diseases associated with angiogenesis and to establish new as well as appropriate angiogenic or anti angiogenic treatment strategies for the future. Nevertheless, angiogenesis is a vigorous process and the techniques to evaluate this process with thorough assessment of physiological characteristics of new blood vessels will be advantageous over the older systems of angiogenesis assessment methods.

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“…[1, 2] In contrast to the use of HIFU for direct thermal ablation, low-intensity ultrasound works together with chemical cytotoxic agents. [3, 4] A few recent studies have reported the use of the combination of chemotherapeutic agents with ultrasound enhances the drug’s anti-cancer effects, and sensitizes drug resistant cells. It was believed that ultrasound-induced cavitation weakens the cell membrane and facilitates the intracellular distribution of drugs.…”

Section: Introductionmentioning

confidence: 99%

Tumor ablation using low-intensity ultrasound and sound excitable drug

Tung

Han

Kim

et al. 2017

Journal of Controlled Release

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The cell membrane is a semi-fluid container that defines the boundary of cells, and provides an enclosed environment for vital biological processes. A sound excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the plasma membrane under gentle ultrasound insonation, 1 MHz, 1 W/cm2. The frequency and power density of insonation are within the physical therapy and medical imaging windows; thus the applied ultrasound is safe and not harmful to tissues. The insertion of SEDs into the plasma membrane is not toxic to cells; however, the intruding SEDs weaken the membrane’s integrity. Under insonation, the ultrasound energy destabilized the SED disrupted membranes, resulting in membrane rupture and eventual cell death. In a xenograft breast tumor model, the SED alone or the ultrasound alone caused little adverse effects to tumor tissue, while the combined treatment triggered necrosis with a brief local insonation of 3 minutes. The described sono-membrane rupture therapy could be a safe alternative to the currently used high-energy tissue ablation technology, which uses X-rays, gamma rays, electron beams, protons, or high- intensity focused ultrasound.

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Development of a Cancer Treatment with the Concomitant Use of Low-Intensity Ultrasound: Entering the Age of Simultaneous Diagnosis and Treatment

Cited by 4 publications

References 26 publications

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells

Assessment Methods of Angiogenesis and Present Approaches for Its Quantification

Tumor ablation using low-intensity ultrasound and sound excitable drug

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