Apoptosis Induction by Ultrasound and Microbubble Mediated Drug Delivery and Gene Therapy

Chen, Z.-Y.; Wang, Y.-X.; Zhao, Yuzheng; Yang, Feng; Liu, J.-B.; Lin, Ye; Liao, Jia‐Yu; Liao, Yue‐Yuan; Zhou, Qiulan

doi:10.2174/1566524014666140804165245

Cited by 9 publications

(7 citation statements)

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“…Studies have shown that ultrasound (US) is one way to induce apoptosis of tumor cells. 5,6 US could induce mitochondrial depolarization, inner mitochondrial membrane permeabilization, and mitochondria-caspase signaling pathway activation 7 along with raised Ca 2+ concentrations and different expression of caspase-3, Bcl-2, and Bax, 6 thus inducing apoptosis of carcinoma cells. However, the apoptosis index induced by US alone at MHz frequencies (such as 1.75 MHz 7 ) is very low (for example 28.33% 7 ), and very strong ultrasonic power is necessary (for example 103.7 W/cm 2 ).…”

Section: Introductionmentioning

confidence: 99%

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Shen

Shao

Zhang

et al. 2020

Exp Biol Med (Maywood)

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Ultrasound and microbubbles can induce apoptosis of tumor cells. However, the effects of ultrasound and microbubbles (USMB) combined with chemotherapy on in vivo tumors have rarely been studied. This research is to evaluate the efficacy of targeted USMB and chemotherapeutic drugs on apoptosis and inhibition of hepatic carcinoma cells in nude mice. We also summarize case reports of its clinical application. It was divided into three parts: First, the subcutaneous hepatic tumors of nude mice were irradiated with ultrasound (20 kHz, 2 W/cm2, 40% duty cycle) and SonoVue microbubbles injected to the tail vein of the mice followed by chemotherapy comprising cisplatin, mitomycin, and 5-fluorouracil. The apoptosis of hepatoma cells was examined by TUNEL staining, and the expression of the Bax and Bcl-2 proteins in the tumor tissues was detected by immunohistochemistry. The microvasculature of the tumor tissues was observed by transmission electron microscope. Second, orthotopic hepatic tumors in nude mice were irradiated by USMB and chemotherapy. The therapeutic effects were evaluated by magnetic resonance imaging. Third, the malignant tumors in three patients were treated with USMB and chemotherapy. Our results showed that microbubbles focused by low-frequency US ruptured microvessel walls, through which more chemotherapy drugs entered into the carcinoma cells, thus enhancing cell apoptosis, increasing Bax protein expression, and decreasing Bcl-2 expression. The survival period of the nude mice in the USMB and chemotherapy group was the longest, compared with the control, USMB, and chemotherapy (χ2=29.37, P < 0.0001). Magnetic resonance imaging examinations revealed the tumor volumes in nude mice decreased after USMB and chemotherapy (t = 3.91, P = 0.0173). In clinical cases, after USMB and chemotherapy, the diameters of tumors decreased and the symptoms of the patients were relieved. Targeted low-frequency ultrasound combined with chemotherapy can promote tumor cell apoptosis, inhibit tumor growth, and relieve clinical symptoms of patients. Impact statement The novelty of this research is that we used ultrasound cavitation to enhance the effects of chemotherapy in the subcutaneous and orthotopic hepatic carcinomas in nude mice. Case reports of the effects of the targeting ultrasound cavitation and chemotherapy on malignant tumors in clinical patients were also examined. We found that low-frequency ultrasound cavitation combined with chemotherapy is effective in the inhibition of tumor growth to some extent.

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Section: Introductionmentioning

confidence: 99%

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Shen

Shao

Zhang

et al. 2020

Exp Biol Med (Maywood)

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“…It is becoming the preferred screening means for fallopian tube obstruction as an alternative for traditional x‐ray–based hysterosalpingography (HSG), due to its cost efficiency, clear images, and nonionizing radiation . However, the sonographic contrast agent, the size of which is half of a red blood cell, is prone to diffusing into blood vessels or lymphatic vessels, which is called intravasation . A recent case report showed that venous intravasation can occur during HyCoSy, causing false‐negative results due to contrast media in the venous plexus …”

Section: Introductionmentioning

confidence: 99%

“…5 However, the sonographic contrast agent, the size of which is half of a red blood cell, is prone to diffusing into blood vessels or lymphatic vessels, which is called intravasation. 6,7 A recent case report showed that venous intravasation can occur during HyCoSy, causing false-negative results due to contrast media in the venous plexus. 8 Although contrast media venous intravasation is unlikely to induce embolism, which can be seen in lipiodol-based HSG, it may increase the risk of the side effects such as pain and infection.…”

Section: Introductionmentioning

confidence: 99%

Influence Factors on Contrast Agent Venous Intravasation During Transvaginal 4‐Dimensional Hysterosalpingo‐Contrast Sonography

Wang

Zhou

et al. 2018

J of Ultrasound Medicine

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“…Therefore, how to induce strong and specific tumor antigen release is a problem faced by tumor treatment. 1In recent years, ultrasound, as a safe and effective method to inhibit tumor growth, can affect tumor hypoxia reaction by inducing mechanical and thermal effects such as oscillation and cavitation, and induce tumor cell apoptosis, thus increasing antigen exposure and stimulating immune response ( Chen et al, 2014 ; Giovagnoli-Vicuña et al, 2022 ) ( Figure 3 Ultrasound combined with microbubbles promotes the release of cancer cell antigens and damages tumor cells). It has been reported that UTMD can lead to apoptosis of tumor cells by acting on ceramide signaling pathway and calcium ion level in tissue environment, while tumor cells that are about to die and undergo stress release immune recognition agents, such as damps, to stimulate the body to produce immune response to tumors ( Wang L. et al, 2021 ; Zhu et al, 2021 ).…”

Section: Mechanism and Application Of Ultrasound Combined With Microb...mentioning

confidence: 99%

Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

Wu,

Li,

Shu

et al. 2024

Front. Pharmacol.

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The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing the therapeutic results. Targeting the tumor microenvironment is a promising cancer treatment method in recent years. The importance of tumor immune microenvironment regulation by ultrasound combined with microbubbles is now widely recognized. Ultrasound and microbubbles work together to induce antigen release of tumor cell through mechanical or thermal effects, promoting antigen presentation and T cells’ recognition and killing of tumor cells, and improve tumor immunosuppression microenvironment, which will be a breakthrough in improving traditional treatment problems such as immune checkpoint blocking (ICB) and himeric antigen receptor (CAR)-T cell therapy. In order to improve the therapeutic effect and immune regulation of TME targeted tumor therapy, it is necessary to develop and optimize the application system of microbubble ultrasound for organs or diseases. Therefore, the combination of ultrasound and microbubbles in the field of TME will continue to focus on developing more effective strategies to regulate the immunosuppression mechanisms, so as to activate anti-tumor immunity and/or improve the efficacy of immune-targeted drugs, At present, the potential value of ultrasound combined with microbubbles in TME targeted therapy tumor microenvironment targeted therapy has great potential, which has been confirmed in the experimental research and application of breast cancer, colon cancer, pancreatic cancer and prostate cancer, which provides a new alternative idea for clinical tumor treatment. This article reviews the research progress of ultrasound combined with microbubbles in the treatment of tumors and their application in the tumor microenvironment.

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Apoptosis Induction by Ultrasound and Microbubble Mediated Drug Delivery and Gene Therapy

Cited by 9 publications

References 0 publications

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Influence Factors on Contrast Agent Venous Intravasation During Transvaginal 4‐Dimensional Hysterosalpingo‐Contrast Sonography

Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

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