Antivascular Ultrasound Therapy Extends Survival of Mice With Implanted Melanomas

Wood, A. K. W.; Schultz, Susan M.; Lee, William M-F.; Bunte, Ralph M.; Sehgal, Chandra M.

doi:10.1016/j.ultrasmedbio.2010.02.001

Cited by 43 publications

(49 citation statements)

References 23 publications

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“…Although such high frequency and pressure pulses are not typically used for drug delivery, temporarily reducing the blood flow could be advantageous to keep the delivered drug in the treated area. The reduced blood flow could also reduce tumour size by itself as has been reported for non-tUCA [197].…”

Section: Enhanced Drug Deliverymentioning

confidence: 61%

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Rooij

Daeichin

Skachkov

et al. 2015

International Journal of Hyperthermia

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Ultrasound contrast agents (UCAs) are used routinely in the clinic to enhance contrast in ultrasonography. More recently, UCAs have been functionalised by conjugating ligands to their surface to target specific biomarkers of a disease or a disease process. These targeted UCAs (tUCAs) are used for a wide range of pre-clinical applications including diagnosis, monitoring of drug treatment, and therapy. In this review, recent achievements with tUCAs in the field of molecular imaging, evaluation of therapy, drug delivery, and therapeutic applications are discussed. We present the different coating materials and aspects that have to be considered when manufacturing tUCAs. Next to tUCA design and the choice of ligands for specific biomarkers, additional techniques are discussed that are applied to improve binding of the tUCAs to their target and to quantify the strength of this bond. As imaging techniques rely on the specific behaviour of tUCAs in an ultrasound field, it is crucial to understand the characteristics of both free and adhered tUCAs. To image and quantify the adhered tUCAs, the state-of-the-art techniques used for ultrasound molecular imaging and quantification are presented. This review concludes with the potential of tUCAs for drug delivery and therapeutic applications.

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Section: Enhanced Drug Deliverymentioning

confidence: 61%

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Rooij

Daeichin

Skachkov

et al. 2015

International Journal of Hyperthermia

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“…Recent studies revealed that ultrasound-stimulated microbubbles (USMBs) induced vessel destruction in tumors [19][20][21]. Compared with antiangiogenic drugs, the microbubble provides ultrasound-guided local treatment to increase the probability of normal tissue sparing during treatment [22].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

Deng

Cai

Feng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded as a promising radiosensitizer. In this study, we investigated the effect of USMBs on the sensitivity of nasopharyngeal carcinoma (NPC) to radiation. Methods: Human NPC (CNE-2) cells and human umbilical vein endothelial cells (HUVECs) were exposed to radiation (0, 2, and 8 Gy) alone or in combination with USMBs. Cell viability and apoptosis were measured with the MTT assay and flow cytometry, respectively. The angiogenic activity of HUVECs was detected using matrigel tubule formation. The in vitro effects induced by these treatments were confirmed in vivo with xenograft models of CNE-2 cells in nude mice by examining vascular integrity using color Doppler flow imaging and cell survival using immunohistochemistry. Additionally, the in vivo and in vitro expressions of angiotensin II (ANG II) and its receptor (AT1R) were detected by immunohistochemistry and western blotting, respectively. With CNE-2 cells and HUVECs transfected with control, ANG II, or AT1R, perindopril (an inhibitor of angiotensin-converting enzyme) and candesartan (an inhibitor of AT1R) were used to verify the role of ANG II and AT1R in the radiosensitivity of tumor and endothelial cells by USMBs, by determining cell viability and apoptosis and angiogenic activity. Results: In the NPC xenografts, USMBs slightly reduced blood flow and CD34 expression, increased tumor cell death and ANG II and AT1R expression, and significantly enhanced the effects of radiation. With CNE-2 cells and HUVECs, the USMBs further enhanced the inhibition of tumor cell viability and endothelial tubule formation and further enhanced the increase in ANG II and AT1R due to radiation. Furthermore, perindopril and candesartan significantly enhanced the inhibitory effect of radiation and USMBs on tumor cell growth and angiogenesis in vitro. Conclusions: We have demonstrated for the first time that USMB exposure can significantly enhance the destructive effect on NPC of radiation, and this effect might be further increased by ANG II and AT1R inhibition. Our findings suggest that USMBs can be used as a promising sensitizer of radiotherapy to treat NPC, and the clinical effect might be increased by ANG II and AT1R inhibition.

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“…In multiple studies of a murine melanoma model, it was consistently demonstrated that tumor insonation (1-3 min treatment time) in the presence of a circulating microbubble had a significant antivascular effect (Wood et al 2005, 2006, 2007, 2008, 2010). Each minute of insonation decreased tumor perfusion by ≈25% (Wood et al 2005).…”

Section: Antivascular Ultrasoundmentioning

confidence: 99%

“…It should be noted that this histologic finding differs from that reported following tumor insonation with high intensity focused ultrasound where acute coagulative necrosis occurs, not only of the neoplastic cells, but also of the tumor vasculature (Van Leenders et al 2005; Wu et al 2001, 2002). These observed bioeffects resulted in a reduced tumor growth rate and a 28% increase in survival time following a single 3 minutes tumor therapy (Wood et al 2010). The antivascular action of low-intensity ultrasound was increased when tumor insonation was at 3 MHz rather than 1 MHz and the temperature of the tumor increased by 5 0 C.min −1 and 2 0 C.min −1 respectively (Wood et al 2008).…”

Section: Antivascular Ultrasoundmentioning

confidence: 99%

A Review of Low-Intensity Ultrasound for Cancer Therapy

Wood

Sehgal

2015

Ultrasound in Medicine & Biology

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287

230

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The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients.

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Antivascular Ultrasound Therapy Extends Survival of Mice With Implanted Melanomas

Cited by 43 publications

References 23 publications

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

A Review of Low-Intensity Ultrasound for Cancer Therapy

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