The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors

Shen, Zhi Yong; Xia, Gan Lin; Wu, Ming; Ji, Lei Yan; Li, Yong Jun

doi:10.1007/s00432-015-2034-y

Cited by 13 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…36 After irradiation with US MB, the tumor vascular walls were injured and ruptured by the shock waves and jet streams induced by inertial cavitation in the nude mice. 37,38 Chemotherapy drugs were given to the animal tail veins. DDP, MMC, and 5-FU entered into the tumor cell tissue through the broken areas of the microvessels produced by the cavitation effect, killing the carcinoma cells and promoting cell apoptosis (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Shen

Shao

Zhang

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Shen

Shao

Zhang

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…The MBs used were an US contrast agent (SonoVue; Bracco SpA, Milan, Italy). The rabbits were anesthetized via an auricular vein injection of 30 mg/kg pentobarbital, which is a routine site for vein injection in rabbits (28).…”

Section: Animal Protocol and Tumor Inoculationmentioning

confidence: 99%

Spiral computed tomography evaluation of rabbit VX2 hepatic tumors treated with 20 kHz ultrasound and microbubbles

Shen

Liu

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. The aim of the present study was to explore the therapeutic effect of 20 kHz ultrasound (US) and microbubbles (MBs) on rabbit VX2 liver tumors by spiral computed tomography (CT) scanning. A total of 16 New Zealand rabbits with hepatic VX2 tumors were divided into four groups: Control, MB, low-frequency US and US + MB. The treatment effect was evaluated by spiral CT scanning prior to, during and following treatment (at 0 weeks and the end of 1 and 2 weeks). The tumor growth rate was recorded. The specimens of VX2 tumors were collected for histological examination and transmission electron microscopy (TEM). No significant differences were observed between tumor areas measured by CT and pathology after 2-week treatment (P>0.05). The mean tumor growth rates in the control, MB, US and US + MB groups after 2 weeks of treatment were 385±21, 353±12, 302±14 and 154±9%, respectively (P<0.05, US + MB vs. the other three groups). Hematoxylin and eosin staining in the US + MB group revealed coagulation necrosis, interstitial hemorrhage and intravascular thrombosis. In the control, MB and US groups, tumor cells exhibited clear nuclear hyperchromatism. TEM of US + MB revealed vascular endothelial cell wall rupture, widened endothelial cell gaps, interstitial erythrocyte leakage and microvascular thrombosis, while intact vascular endothelial cells and normal erythrocytes in the tumor vessels were observed in the control, MB and US groups. A combination of 20 kHz US and MBs may effectively inhibit rabbit VX2 tumors. Spiral CT scanning is an ideal method to evaluate the US treatment on rabbit tumors.

show abstract

“…Currently, sonoporation has been used for different tissues, such as cardiovascular system (Unger et al., 2014 ), breast cancer (Bai et al., 2015 ), liver cancer (Zhang et al., 2016 ; Shen et al., 2016 ), pancreatic cancer (Kotopoulis et al., 2014 ), endothelial cells (Skachkov et al., 2014 ), and kidney tubules (Kurosaki et al., 2014 ). However, the transfection efficiency of sonoporation is subjected to several factors including the frequency and intensity of ultrasound wave, ultrasound pressure, and exposure duration (Mehier-humbert & Guy, 2005 ; Al-Dosari & Gao, 2009 ).…”

Section: Physical Methods Of Gene Deliverymentioning

confidence: 99%

Advanced physical techniques for gene delivery based on membrane perforation

et al. 2018

View full text Add to dashboard Cite

Gene delivery as a promising and valid tool has been used for treating many serious diseases that conventional drug therapies cannot cure. Due to the advancement of physical technology and nanotechnology, advanced physical gene delivery methods such as electroporation, magnetoporation, sonoporation and optoporation have been extensively developed and are receiving increasing attention, which have the advantages of briefness and nontoxicity. This review introduces the technique detail of membrane perforation, with a brief discussion for future development, with special emphasis on nanoparticles mediated optoporation that have developed as an new alternative transfection technique in the last two decades. In particular, the advanced physical approaches development and new technology are highlighted, which intends to stimulate rapid advancement of perforation techniques, develop new delivery strategies and accelerate application of these techniques in clinic.

show abstract

The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors

Abstract: Percutaneous ethanol injection followed by low-frequency ultrasound and microbubbles can be effective in inhibiting rabbit liver tumors and prolonging survival time.

Cited by 13 publications

References 22 publications

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

Spiral computed tomography evaluation of rabbit VX2 hepatic tumors treated with 20 kHz ultrasound and microbubbles

Advanced physical techniques for gene delivery based on membrane perforation

Contact Info

Product

Resources

About