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Using the Promise of Sonodynamic Therapy in the Clinical Setting against Disseminated Cancers.

Trendowski M - Chemother Res Pract (2015)

Bottom Line: Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure.Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines.Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA.

ABSTRACT
Sonodynamic therapy (SDT) is a form of ultrasound therapy in which specialized chemotherapeutic agents known as sonosensitizers are administered to increase the efficacy of ultrasound-mediated preferential damage of neoplastic cells. Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure. As supportive as the data have been, assessment of this method at the clinical level has been limited to only solid tumors. Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines. Potential procedures to administer SDT to leukemia patients are heating the appendages as ultrasound is applied to these areas (Heat and Treat), using an ultrasound probe to scan the body for malignant growths (Target and Destroy), and extracorporeal blood sonication (EBS) through dialysis. Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered.

No MeSH data available.


Related in: MedlinePlus

Antineoplastic mechanisms of ultrasound. (a) Microbubbles are unevenly stretched by ultrasonic waves, causing an unequal distribution of force known as inertial cavitation. Microbubbles oscillating in a stable motion reflect stable cavitation, while the expansion and contraction of microbubbles that are unequal and markedly exaggerated are indicative of inertial cavitation. Subsequent stress results in microbubble implosion, creating considerable amounts of energy. (b) The energy provided by the collapse of microbubbles potentiates the formation of sonoluminescent light within the cell. The light subsequently activates endogenous compounds within the cell that release ROS when returning to the ground state. (c) Many tumors rely on angiogenesis to sustain increased metabolic activity. Microbubbles can enter the tumor vasculature, and at sufficiently high amplitudes, ultrasound induces significant vascular damage, shutting down blood flow. The vessels develop and harbor hypoxic regions, causing oxidative stress; lack of nutrients and increased acidity induce apoptosis. In addition, malignant cells exposed to ultrasound often undergo apoptosis through the intrinsic pathway. Caspase-3 is upregulated by proteins such as Bax and Bak that integrate into the mitochondrial membrane, facilitating apoptotic signaling. It is important to note that sonosensitizers have been developed to significantly increase the efficacy of each mechanism. Images courtesy of [1].
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fig1: Antineoplastic mechanisms of ultrasound. (a) Microbubbles are unevenly stretched by ultrasonic waves, causing an unequal distribution of force known as inertial cavitation. Microbubbles oscillating in a stable motion reflect stable cavitation, while the expansion and contraction of microbubbles that are unequal and markedly exaggerated are indicative of inertial cavitation. Subsequent stress results in microbubble implosion, creating considerable amounts of energy. (b) The energy provided by the collapse of microbubbles potentiates the formation of sonoluminescent light within the cell. The light subsequently activates endogenous compounds within the cell that release ROS when returning to the ground state. (c) Many tumors rely on angiogenesis to sustain increased metabolic activity. Microbubbles can enter the tumor vasculature, and at sufficiently high amplitudes, ultrasound induces significant vascular damage, shutting down blood flow. The vessels develop and harbor hypoxic regions, causing oxidative stress; lack of nutrients and increased acidity induce apoptosis. In addition, malignant cells exposed to ultrasound often undergo apoptosis through the intrinsic pathway. Caspase-3 is upregulated by proteins such as Bax and Bak that integrate into the mitochondrial membrane, facilitating apoptotic signaling. It is important to note that sonosensitizers have been developed to significantly increase the efficacy of each mechanism. Images courtesy of [1].

Mentions: Sonodynamic therapy (SDT) is a promising novel treatment modality that has yielded impressive anticancer effects in both in vitro and in vivo studies. It has been repeatedly demonstrated that ultrasound preferentially damages malignant cells based on the size differential between such cells and those of normal histology [1]. SDT is a form of ultrasound therapy in which specialized agents known as sonosensitizers are administered to increase the extent of preferential damage exerted by ultrasound against neoplastic cells (Figure 1). Preliminary studies examining the antineoplastic potential of sonosensitizers focused on the propensity of ultrasound to activate reactive oxygen species (ROS) producing agents, thereby eliciting oxidative stress that preferentially induced apoptosis in malignant cells [2–5]. Since then, the list of potential sonosensitizers has grown tremendously and has diversified to include cytoskeletal-directed agents, echo contrast agents, and vascular disrupting agents [1]. Multiple comprehensive literature reviews have been compiled that provide detailed explanations of the mechanisms that allow SDT to preferentially damage neoplastic tissue under conditions that do not notably perturb normal cells [1, 6–9]. These references comprehensively review the mechanisms illustrated in Figure 1 and should be referred to for further explanation.


Using the Promise of Sonodynamic Therapy in the Clinical Setting against Disseminated Cancers.

Trendowski M - Chemother Res Pract (2015)

Antineoplastic mechanisms of ultrasound. (a) Microbubbles are unevenly stretched by ultrasonic waves, causing an unequal distribution of force known as inertial cavitation. Microbubbles oscillating in a stable motion reflect stable cavitation, while the expansion and contraction of microbubbles that are unequal and markedly exaggerated are indicative of inertial cavitation. Subsequent stress results in microbubble implosion, creating considerable amounts of energy. (b) The energy provided by the collapse of microbubbles potentiates the formation of sonoluminescent light within the cell. The light subsequently activates endogenous compounds within the cell that release ROS when returning to the ground state. (c) Many tumors rely on angiogenesis to sustain increased metabolic activity. Microbubbles can enter the tumor vasculature, and at sufficiently high amplitudes, ultrasound induces significant vascular damage, shutting down blood flow. The vessels develop and harbor hypoxic regions, causing oxidative stress; lack of nutrients and increased acidity induce apoptosis. In addition, malignant cells exposed to ultrasound often undergo apoptosis through the intrinsic pathway. Caspase-3 is upregulated by proteins such as Bax and Bak that integrate into the mitochondrial membrane, facilitating apoptotic signaling. It is important to note that sonosensitizers have been developed to significantly increase the efficacy of each mechanism. Images courtesy of [1].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4562321&req=5

fig1: Antineoplastic mechanisms of ultrasound. (a) Microbubbles are unevenly stretched by ultrasonic waves, causing an unequal distribution of force known as inertial cavitation. Microbubbles oscillating in a stable motion reflect stable cavitation, while the expansion and contraction of microbubbles that are unequal and markedly exaggerated are indicative of inertial cavitation. Subsequent stress results in microbubble implosion, creating considerable amounts of energy. (b) The energy provided by the collapse of microbubbles potentiates the formation of sonoluminescent light within the cell. The light subsequently activates endogenous compounds within the cell that release ROS when returning to the ground state. (c) Many tumors rely on angiogenesis to sustain increased metabolic activity. Microbubbles can enter the tumor vasculature, and at sufficiently high amplitudes, ultrasound induces significant vascular damage, shutting down blood flow. The vessels develop and harbor hypoxic regions, causing oxidative stress; lack of nutrients and increased acidity induce apoptosis. In addition, malignant cells exposed to ultrasound often undergo apoptosis through the intrinsic pathway. Caspase-3 is upregulated by proteins such as Bax and Bak that integrate into the mitochondrial membrane, facilitating apoptotic signaling. It is important to note that sonosensitizers have been developed to significantly increase the efficacy of each mechanism. Images courtesy of [1].
Mentions: Sonodynamic therapy (SDT) is a promising novel treatment modality that has yielded impressive anticancer effects in both in vitro and in vivo studies. It has been repeatedly demonstrated that ultrasound preferentially damages malignant cells based on the size differential between such cells and those of normal histology [1]. SDT is a form of ultrasound therapy in which specialized agents known as sonosensitizers are administered to increase the extent of preferential damage exerted by ultrasound against neoplastic cells (Figure 1). Preliminary studies examining the antineoplastic potential of sonosensitizers focused on the propensity of ultrasound to activate reactive oxygen species (ROS) producing agents, thereby eliciting oxidative stress that preferentially induced apoptosis in malignant cells [2–5]. Since then, the list of potential sonosensitizers has grown tremendously and has diversified to include cytoskeletal-directed agents, echo contrast agents, and vascular disrupting agents [1]. Multiple comprehensive literature reviews have been compiled that provide detailed explanations of the mechanisms that allow SDT to preferentially damage neoplastic tissue under conditions that do not notably perturb normal cells [1, 6–9]. These references comprehensively review the mechanisms illustrated in Figure 1 and should be referred to for further explanation.

Bottom Line: Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure.Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines.Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA.

ABSTRACT
Sonodynamic therapy (SDT) is a form of ultrasound therapy in which specialized chemotherapeutic agents known as sonosensitizers are administered to increase the efficacy of ultrasound-mediated preferential damage of neoplastic cells. Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure. As supportive as the data have been, assessment of this method at the clinical level has been limited to only solid tumors. Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines. Potential procedures to administer SDT to leukemia patients are heating the appendages as ultrasound is applied to these areas (Heat and Treat), using an ultrasound probe to scan the body for malignant growths (Target and Destroy), and extracorporeal blood sonication (EBS) through dialysis. Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered.

No MeSH data available.


Related in: MedlinePlus