Induction of the apoptosis of cancer cell by sonodynamic therapy:a review

Ultrasound can be used not only in examination, but also in therapy, especially in the therapy of cancer. Sonodynamic therapy is an experimental cancer therapy method which uses ultrasound to enhance the cytotoxic effects of agents known as sonosensitizers. It has been tested in vitro and in vivo. The ultrasound could penetrate the tissue and cell under some of conditions which directly changes cell membrane permeability, thereby allowing the delivery of exogenous molecules into the cells in some degree. Ultrasound could inhibit the proliferation or induce the apoptosis of cancer cells in vitro or in vivo. Recent researches indicated low-frequency and low-intensity ultrasound could induce cell apoptosis, which could be strengthened by sonodynamic sensitivity, microbubbles, chemotherapeutic drugs and so on. Most kinds of ultrasound suppressed the proliferation of cancer cells through inducing the apoptosis of cancer cells. The mechanism of apoptosis is not clear. In this review, we will focus on and discuss the mechanisms of the induction of cancer cell apoptosis by ultrasound.

Theoretical Calculation of a Focused Acoustic Field from a Linear Phased Array on a Concave Cylindrical Transducer

A new linear phased array on a concave cylindrical transducer is designed for meeting the specific requirements of applications for interstitial thermal ablation.Using the array,a focal line can be generated rapidly and the focal position can be adjusted in the proper range without the use of complex mechanical structures.The focused acoustic field distributions in the axial,radial and azimuthal directions of the transducer are investigated theoretically by numerical simulation.Effects of the focal distance,steering angle,element arc-width,arc-space between adjacent elements and number of elements on the acoustic field are also thoroughly studied.Many important results are obtained.

Treatment of PC-3 cells with ultrasound combined with microbubbles induces distinct alterations in the expression of Bcl-2 and Bax

The objective of the present study was to investigate whether ultrasound combined with microbubbles induces apoptotic cell death in androgen-independent prostate cancer cells and to identify the probable mechanism.We used ultrasound in continuous wave mode with a frequency of 21 kHz and a spatial-average temporal-average intensity of 46 mW/cm2.Ultrasound combined with microbubbles(200μL SonoVue)was used to treat androgen-independent human prostate cancer PC-3 cells for 30 s.PC-3 cells were divided into three groups:the control group,the ultrasound group and the ultrasound combined with microbubbles group.Immediately after treatment,trypan blue exclusion was used to assess cell viability.Cell apoptosis at 24 h after treatment was measured using transmission electron microscopy and flow cytometry.Western blotting was used to evaluate the expression of the apoptosis-related proteins,Bcl-2 and Bax.Ultrasound combined with microbubbles had a minimal effect on the viability of PC-3cells and induced minimal levels of cell lysis.The level of apoptosis in PC-3 cells induced by this modality was significantly higher than in controls(12.77±0.31%vs.2.56±0.22%,P<0.01).Treatment with ultrasound combined with microbubbles increased the expression of Bax,a pro-apoptotic protein,and decreased the expression of Bcl-2,an anti-apoptotic protein.It was concluded that ultrasound combined with microbubbles induces apoptotic cell death in human prostate cancer PC-3 cells through down-regulation of Bcl-2 and up-regulation of Bax.

Excavating bioactivities of nanozyme to remodel microenvironment for protecting chondrocytes and delaying osteoarthritis

Osteoarthritis(OA)is the main cause of disability in the elderly.Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease,and reduce the probability of joint replacement.However,there is to date no effective intervention for early and middle-stage OA.OA microenvironment mainly destroys the balance of oxidative stress,extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors.Herein,hollow Prussian blue nanozymes(HPBzymes)were designed via a modified hydrothermal template-free method.The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA.The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo,remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species(ROS)and Rac1/nuclear factor kappa-B(NF-κB)signaling in a rat model.HPBzyme significantly diminished interleukin(IL)-1β-stimulated inflammation,extracellular matrix degradation,and apoptosis of human chondrocytes.HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB.Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases.This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.

Focused ultrasound induces apoptosis in pancreatic cancer cells

Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades. Focused ultrasound （FU） has been somewhat successful in treating pancreatic cancer. The purpose of this study was to investigate apoptosis in pancreatic cancer cells induced by FU. Methods Suspension of human pancreatic carcinoma cell line PaTu 8988t was radiated by FU, using five doses with different radiation parameters and patterns, including one blank control. Temperature increase of the cell suspension was monitored. Cell apoptosis and death after FU radiation was observed using fluorescence microscopy and was tested by flow cytometer at 3, 6, 12, 24, and 48 hours after ultrasound radiation. Results The maximum cell suspension temperatures following five radiation doses were 28℃, （42.20±2.17）℃, （50.80±0.84）℃, （55.80±2.17）℃, and （65.20±3.11）℃; differences between the doses were statistically significant （P 〈0.05）. The apoptosis rate peaked at 24 hours after radiation, at （0.56±0.15）%, （1.28±0.16）%, （1.84±0.29）%, （5.74±1.15）%, and （2.00±0.84）% for the five doses; differences between the doses were statistically significant （P 〈0.05）. Between doses 1--4, cell apoptosis rates increased as the Tmax increased, in dose 5, as the Tmax was above 60℃, the apoptosis rate decreased. Conclusion Sub-threshold thermal exposures of FU radiation with a continuous radiation pattern could result in higher percentage of apoptosed cells.

Assessment of alternated cooling and heating treatment by US combined CEUS in the VX2 rabbit liver tumor model

Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue.Thermal–physical treatment has many advantages,but treatment by freezing or heating alone has some limitations.By taking the advantages and disadvantages of cryosurgery and thermotherapy into consideration,a new thermal technique that combines cryosurgery and radio frequency ablation has been proposed,thereby overcoming the disadvantages of each treatment strategy and improving therapeutic outcomes.This new approach remains to be systematically studied in the liver;therefore,this study was performed to estimate survival after alternated cooling and heating ablation therapy in a VX2 rabbit liver tumor model.Sixteen days after VX2 carcinoma implantation into the rabbit liver,tumors were treated with alternated cooling and heating ablation therapy.Rabbits were monitored for 6 months after treatment and assessed with ultrasound(US)and computed tomography at 1,7,14,and 30 days posttreatment.Untreated tumor-bearing animals served as the control group.Our results show that alternate freezing and heating ablation therapy resulted in a good recovery of VX2 rabbits.Compared with the control group,treated rabbits lived significantly longer(P\0.05),with 70%of treated animals surviving to 196 days posttreatment without metastasis or recurrence,while none of the controls did so.There was no local recurrence in the treatment group.All rabbits in the control group developed metastasis,while metastasis was only observed in 30% of treated rabbits.These results suggest that alternate cooling and heating ablation therapy can prolong the survival time of rabbits with VX2 liver tumors and is an effective method for tumor therapy.Furthermore,we also showed in this model that contrast enhanced US is a valid follow-up approach to assess treatment effectiveness.

Modeling of Focused Acoustic Field of a Concave Multi-annular Phased Array Using Spheroidal Beam Equation

A theoretical model of focused acoustic field for a multi-annular phased array on concave spherical surface is proposed.In this model,the source boundary conditions of the spheroidal beam equation(SBE) for multi-annular phased elements are studied.Acoustic field calculated by the dynamic focusing model of SBE is compared with numerical results of the O'Neil and Khokhlov-Zabolotskaya-Kuznetsov(KZK) model,respectively.Axial dynamic focusing and the harmonic effects are presented.The results demonstrate that the dynamic focusing model of SBE is good valid for a concave multi-annular phased array with a large aperture angle in the linear or nonlinear field.

Self-reciprocity calibration for spherical transducers based on acoustic reflection from the inside wall of a spherical shell

B ased on the emission of pulsed spherical acoustic waves from a spherical transducer and their reflection from the inside wall of a concentric spherical shell,the electromechanical reciprocity theorem is applied to derive a reciprocity coefficient for the calibration of a spherical transducer in a spherical acoustic field.First,a self-reciprocity calibration method using a closed spherical shell reflector is proposed to obtain the five fundamental electroacoustic parameters of the spherical transducer from a single measurement.Further,a conversion factor is given for converting the voltage sensitivity obtained by the current method to the standard sensitivity defined in plane wave fields.To determine this conversion factor,a method is developed for measuring the scattering coefficient of the transducer.Calibration of a 10-mm-radius spherical transducer was performed in the frequency range 25 kHz to 63 kHz.The results showed that the standard uncertainty of the measured voltage sensitivity was up-bounded by 0.9 dB.

Correlation of placenta previa type with cesarean section blood toss and predictors of hysterectomy

To the Editor:Placenta previa is one of the main causes of bleeding in late pregnancy and childbirth.According to the relationship between the lower edge of the placenta and the internal cervix,placenta previa can be classified as incomplete placenta previa(IPP)and complete placenta previa(CPP).IPP indicates that the lower edge of the placenta reaches but does not exceed the internal cervix.CPP refers the lower edge of the placenta covering and exceeding the internal cervix.