Ultrasound-propelled liposome circumvention and siRNA silencing reverse BRAF mutation-arised cancer resistance to trametinib.

BRAF-V600E mutation is regarded as the source of lung cancer resistance to trametinib (Tr), and no solution available for completely addressing this intractable resistance has emerged yet. Herein, the combination of ultrasonic (US) propelled folic acid (FA)-modified liposomes strategy and BRAF-driven gene silencing program is proposed to effectively reverse Tr's resistance to lung cancer. Meanwhile, the prepared cationic nanoliposomes can assist Tr drug and BRAF siRNA to escape lysosome disposal, thereby avoiding Tr drug pumping out or siRNA degradation. More significantly, loaded BRAF siRNA is designed to silence BRAF-V600E mutation genes via modulating BRAF-ERK-pathway and remarkably reverse the PC9R resistance to Tr. Systematic experiments validate that these cooperatively sensitize PC9R cells to Tr and shrink resistant NSCLC in vivo, especially after combining with FA-mediated targeting and US-enhanced permeability that permits more intratumoral accumulations of Tr. Such a biocompatible targeting drug-resistance liberation agent and its underlying design strategy lay a foundation avenue to completely reverse tumor resistance, which is preferable to treat BRAF mutation-arised resistance of various tumors, holding high clinical translation potentials.

Cranial Nerve Anatomy Using a Modular and Multimodal Radiologic Approach.

Introduction: Medical students often struggle with learning cranial nerve anatomy. Typically, cranial nerve anatomy is taught using didactic lectures and textbook illustrations, often leaving students frustrated. Methods: We developed a multimodal radiologic approach to teaching cranial nerve anatomy. First, 150 students were presented with carefully curated preclass material from which to prepare. Next, they received a didactic lecture that was recorded for them to revisit on their own time. Last, students worked in groups in a lab setting with expert radiologists to identify the cranial nerves and related anatomy and learn about some basic pathophysiology. We used a pretest and posttest to examine the effectiveness of our teaching methods and a survey to measure students' satisfaction. Results: Student knowledge of cranial nerve structure was significantly improved after our module, with quiz scores increasing from 4.6 to 6.8 out of 9.0 (p < .001). In addition, students reported feeling more confident in their knowledge of the material and offered high satisfaction scores. Discussion: The breadth of knowledge covered during the preclinical training years continues to expand despite stable or even contracted durations of training, requiring knowledge to be delivered in an ever more efficient manner. Ultimately, the multimodal pedagogy used by our resource leads to students who are more confident and engaged in their learning, resulting in increased knowledge.

Marriage of Virus-Mimic Surface Topology and Microbubble-Assisted Ultrasound for Enhanced Intratumor Accumulation and Improved Cancer Theranostics.

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an "intrinsic plus extrinsic superiority" administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus-mimic surface topology of the nanoparticles for enhanced nano-bio interactions. Meanwhile, the extrinsic stimuli of microbubble-assisted low-frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics.

Targeted theranostics of lung cancer: PD-L1-guided delivery of gold nanoprisms with chlorin e6 for enhanced imaging and photothermal/photodynamic therapy.

Peptide modified nanoparticles have emerged as powerful tools for enhanced cancer diagnosis and novel treatment strategies. Here, human programmed death-ligand 1 (PD-L1) peptides were used for the first time for the modification of gold nanoprisms (GNPs) to enhance targeting efficiency. A multifunctional nanoprobe was developed that the GNPs@PEG/Ce6-PD-L1 peptide (GNPs@PEG/Ce6-P) was used for imaging-guided photothermal/photodynamic therapy by using the targeting effect of PD-L1. Both confocal imaging and flow cytometry experiments demonstrated a remarkable affinity of the as-prepared nanoprobes GNPs@PEG/Ce6-P to lung cancer cells (HCC827), which have a high PD-L1 expression. Subsequent in vitro and in vivo experiments further demonstrated that the nanoprobes GNPs@PEG/Ce6-P not only allowed for real-time visualization via fluorescence (FL) imaging and photoacoustic (PA) imaging, but also served as phototherapy agents for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, treatments on human lung cancer cells-derived tumors demonstrated that the nanoprobes GNPs@PEG/Ce6-P could significantly suppress tumor growth through PTT and PDT from GNPs and Ce6, respectively. In conclusion, the as-prepared new nanoprobes show promising potential for nanomedicine with remarkable targeting ability for dual-mode imaging and enhanced PDT and PTT effects on lung cancer.

Validation and Testing of an E-Learning Module Teaching Core Urinary Incontinence Objectives in a Randomized Controlled Trial.

OBJECTIVES: To evaluate the efficacy of a urinary incontinence (UI) e-learning module (ELM) in undergraduate medical education. METHODS: An ELM was developed and validated to teach on UI learning objectives. A 21-item assessment was developed to test knowledge gained. A randomized-controlled trial and parallel nested-cohort study were performed to test the effectiveness of the validated UI-ELM compared with standard methods of UI learning. Students were recruited and enrolled at the onset of their obstetrics and gynecology clerkship. Assignments to either a week-long rotation of gynecologic (GYN) or urogynecologic (UroGyn) surgery were made independent of the study protocol. On the GYN rotation, students were randomly assigned to the UI-ELM intervention or no intervention (control group). The nested-cohort comprised students assigned to the UroGyn rotation. Parametric statistics were applied assessing score changes between the UI-ELM versus control/UroGyn groups. RESULTS: Eighty-three students rotated between June 2015 and February 2016. Fifty-five were assigned to GYN and randomized: 35 UI-ELM versus 20 no intervention; 28 were assigned to UroGyn. Students randomized to the UI-ELM had greater score improvement compared with controls (between group difference of +2.73; 95% confidence interval, 0.53-4.93; P = 0.02). Knowledge improvement was similar between students exposed to the UI-ELM compared with those with UroGyn exposure (between group difference, +0.91; 95% confidence interval, -1.05 to 2.88; P = 0.35). CONCLUSIONS: The UI-ELM resulted in greater improvement in UI knowledge among third year medical students compared with traditional methods of learning and similar to those exposed to a UroGyn rotation.

[Galectin3 Regulates Transforming Growth Factor-ß-induced Epithelial-mesenchymal].

Objective To explore the role of Galectin3 in transforming growth factor-ß(TGF-ß)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Methods Galectin3 was over-expressed in an A549 cell line. EMT was induced in lung cancer A549 cells by adding TGF-ß. The expressions of Galectin3,E-cadherin,and vimentin were determined by Western blot. The protein expression of E-cadherin and the morphological changes of the cells were detected by immunofluorescence. Cellular proliferation was analyzed with cell counting kit-8,and the cellular migration and invasion was measured by scratches healing and Transwell assay,respectively.Results When only Galectin3 was over-expressed in A549 cell line,the expression levels of EMT-related proteins such as E-cadherin and vimentin were not changed,and the abilities of cellular proliferation,invasion,and migration were not changed either. When the EMT was induced by TGF-ß in A549 cells,the E-cadherin expression was down-regulated and the vimentin expression was up-regulated in A549 cells with Galectin3 over-expression. There was no significant change in cellular proliferation,whereas the abilities of cellular invasion and migration were enhanced.Conclusion The TGF-ß-induced EMT in A549 cells can be enhanced by Galectin3.

WNT-activated bone grafts repair osteonecrotic lesions in aged animals.

The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.

Assessing Bone Type of Implant Recipient Sites by Stereomicroscopic Observation of Bone Core Specimens: A Comparison With the Assessment Using Dental Radiography.

BACKGROUND: The aim of the study is to determine if bone quality evaluation of surgically obtained bone core specimens using a stereomicroscope is reliable for determining bone quality at implant recipient sites. METHODS: Bone quality was presurgically assessed in 122 edentulous ridges obtained from 62 patients using periapical radiographs and categorized according to the Lekholm and Zarb classification. During surgery, bone specimens were trephined, and bone types were immediately classified using a stereomicroscope. Microarchitectural characteristics of bone cores were evaluated after being scanned using microcomputed tomography (micro-CT). RESULTS: Bone types of implant sites categorized from radiography and stereomicroscope had statistically similar distribution but poor interrater agreement. Using micro-CT, maxillae and mandibles showed significant differences in microarchitectural characteristics of bone cores. Bone volume (BV), total volume (TV), and trabecular thickness (Tb.Th) increased, whereas bone surface density (BS/BV) and open porosity (Po.[Op]) decreased in mandibular bone cores compared with those in maxillary bone cores. Moreover, micro-CT values of BV/TV and Po.(Op) statistically correlated with bone types assessed by stereomicroscopy, particularly in mandibles (adjusted means of BV/TV of Type 2 to 4 versus Type 1 decreasing from -9.88%, -15.09%, -29.31%; those of Po.(Op) ranged from 9.77%, 15.06%, 29.52% in an upward trend). However, such correlations were not found in maxillae or when bone types were classified using periapical radiographs. CONCLUSIONS: Caution is needed when using presurgical periapical radiographs to predict bone quality at implant recipient sites. Surgically preserved bone core specimens, whenever obtainable, might offer additional information to accurately assess bone quality, particularly at mandibular implant sites.

Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions.

Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN.

Clinical and Microcomputed Topography Evaluation of the Concentrated Growth Factors as a Sole Material in a Cystic Bony Defect in Alveolar Bone Followed by Dental Implantation: A Case Report.

Concentrated growth factors (CGFs) can be used to enhance wound healing. This case report describes a short-term effect of CGF grafting followed by implant placement in a cystic bony defect within the mandible. Healing conditions were monitored by 2 implant-related surgeries, radiographs, and a microcomputed topography examination. Continuous increase of radiopacity in radiographs was noticed till 6 months after grafting. Bone core specimen was taken at 3.5 months after grafting, and percent bone volume reached 32.7% analyzed by microcomputed topography. In conclusion, the present case showed bone regeneration in the cystic bony defect grafted by CGFs alone.

Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique.

Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results.

Upregulation of ULK1 expression in PC-3 cells following tumor protein P53 transfection by sonoporation.

The aim of the present study was to investigate whether ultrasound combined with microbubbles was able to enhance liposome-mediated transfection of genes into human prostate cancer cells, and to examine the association between autophagy and tumor protein P53 (P53). An MTT assay was used to evaluate cell viability, while flow cytometry and fluorescence microscopy were used to measure gene transfection efficiency. Autophagy was observed using transmission electron microscopy. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to assess the expression of autophagy-associated genes. The results of the present study revealed that cell viability was significantly reduced following successfully enhanced transfection of P53 by ultrasound combined with microbubbles. In addition, serine/threonine-protein kinase ULK1 levels were simultaneously upregulated. Castration-resistant prostate cancer is difficult to treat and is investigated in the present study. P53 has a significant role in a number of key biological functions, including DNA repair, apoptosis, cell cycle, autophagy, senescence and angiogenesis. Prior to the present study, to the best of our knowledge, increased transfection efficiency and reduced side effects have been difficult to achieve. Ultrasound is considered to be a 'gentle' technique that may be able to achieve increased transfection efficiency and reduced side effects. The results of the present study highlight a potential novel therapeutic strategy for the treatment of prostate cancer.

Upregulation of Beclin-1 expression in DU-145 cells following low-frequency ultrasound irradiation combined with microbubbles.

Castration-resistant prostate cancer (PCa) is difficult to treat. Autophagy, which is an evolutionarily conserved mechanism, plays an important role in cancer development. The balance between cell death and survival in different stages varies in cancer development. The role of autophagy in PCa development has not yet been fully elucidated. Ultrasound may be of value in the treatment of PCa. The aim of the present study was to investigate the association between autophagy and ultrasound combined with microbubbles. The MTT assay was used to evaluate cell viability. Autophagy was observed by transmission electron microscopy. Reverse transcription-polymerase chain reaction and western blot analysis were used to assess the expression of autophagy-related genes. The results revealed that cell viability was significantly reduced by ultrasound combined with microbubbles in DU145 PCa cells. The present study demonstrated that ultrasound combined with microbubbles induced autophagy and autophagy-related DU-145 cell death. Notably, these findings highlighted additional mechanisms that suggest the potential of ultrasound-modulated autophagy as a novel therapeutic strategy for PCa.

Diagnostic performance of the automated breast volume scanner: a systematic review of inter-rater reliability/agreement and meta-analysis of diagnostic accuracy for differentiating benign and malignant breast lesions.

OBJECTIVES: To investigate the inter-rater reliability and agreement of the automated breast volume scanner (ABVS) and the diagnostic accuracy for differentiating malignant and benign lesions. The overall aim was to find out if the ABVS is applicable to daily clinical practice. METHODS: Qualifying studies were retrieved from Pubmed, EMBASE, Cochrane Library, Biosis Preview, CBM disc and by manual search and reference lists up to 30 September 2014. Pooled sensitivity and specificity of ABVS were calculated and summary receiver operating characteristic curves were drawn. RESULTS: Thirteen studies were included in the meta-analysis of diagnostic accuracy and seven studies were included in the systematic review of inter-rater reliability/agreement of ABVS. For 'diagnostic accuracy', the pooled values of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 92 % (95 % CI 89.9-93.8), 84.9 % (82.4-87.0), 6.172 (4.364-8.730), 0.101 (0.075-0.136), and 72.226 (39.637-131.61), respectively. For the studies of inter-rater reliability/agreement, the quality was heterogeneous and no evidenced result can be pooled. CONCLUSIONS: Sensitivity and specificity of ABVS for differentiating malignant and benign breast lesions were high. More sound studies focusing on inter-rater reliability/agreement of ABVS, which deeply affect the clinical utilization and generalization of ABVS, are urgently needed. KEY POINTS: • ABVS has high sensitivity and specificity in differentiating malignant and benign breast lesions. • The quality of published inter-rater reliability studies is heterogeneous. • Empirical evidence concerning the inter-rater reliability/agreement for the ABVS is rare. • Comparison studies on ABVS and other medical imaging examinations are warranted.

Cyclosporine A enhances gingival ß-catenin stability via Wnt signaling.

BACKGROUND: Cyclosporine A (CsA) increases ß-catenin messenger RNA (mRNA) and protein expression. The present study demonstrates that Wnt/ß-catenin signaling inhibits ß-catenin degradation in the gingiva. METHODS: Forty 5-week-old male Sprague-Dawley rats were assigned to two study groups after healing from right maxillary molar extractions. The rats in the experimental group were fed 30 mg/kg CsA daily for 4 weeks, whereas the control rats were fed mineral oil. At the end of the study, all rats were sacrificed, and the gingivae were obtained. The gingival morphology after CsA treatment was evaluated by histology, and the genes related to Wnt/ß-catenin signaling were initially screened by microarray. Polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the mRNA and protein expression of proliferating cell nuclear antigen, cyclin D1, E-cadherin, ß-catenin, Dvl-1, glycogen synthase kinase-3ß, axin-1, and adenomatous polyposis coli (APC). Phosphoserine and ubiquitinylated ß-catenin were detected after immunoprecipitation. RESULTS: In rats treated with CsA, overgrowth of gingivae was observed, and altered expression of genes related to Wnt/ß-catenin signaling was detected by the microarray. The gingival mRNA and protein expression profiles for genes associated with Wnt/ß-catenin signaling further confirmed the effect of CsA: ß-catenin and Dvl-1 expression increased, but APC and axin-1 expression decreased. Western blotting and immunohistochemistry showed decreases in ß-catenin serine phosphorylation (33/37) and ubiquitinylation in the gingivae of CsA-treated rats. CONCLUSION: CsA-enhanced gingival ß-catenin stability may be involved in gene upregulation or ß-catenin degradation via the Wnt/ß-catenin pathway.

Risk factors of venous thrombosis in patients with ankle fractures.

AIM: Deep vein thrombosis (DVT) is a major complication that can occur after injuries. our aim was to explore the incidence and risk factors of venous thromboembolism in patients with ankle fractures. METHODS: Consecutive patients with an isolated fracture of the ankle presenting at our centre between Sept 2004 and May 2012 were studied. They were investigated for venous thrombosis by Doppler sonography (DUS) before surgery. Univariate and multivariate logistic regressions analyses were performed to identify the incidence and risk factors for venous thromboembolism. RESULTS: A total of 2347 patients were studied in the research. Of these, only 119 patients suffered from DVT. The multivariable analyses showed that diabetes, less activity and the time from injury were the key risk factors for thrombosis. CONCLUSION: In patients with ankle fracture, the risk of thrombosis was low and it may not need warrant routine thromboprophylaxis. However, most cases had no significant symptoms, is necessary to grasp the indications for high risk patients to reduce the incidence rate of venous thrombosis.

Enhanced antitumor effects of low-frequency ultrasound and microbubbles in combination with simvastatin by downregulating caveolin-1 in prostatic DU145 cells.

Advanced prostate cancer is difficult to treat due to androgen resistance, its deep location and blood tumor barriers. Low-frequency ultrasound (LFU) has potential clinical applications in the treatment of prostate cancer due to its strong penetrability and high sensitivity towards tumor cells. Simvastatin has often been administered as a preventive agent in prostate tumors. The aim of the present study was to investigate the enhanced effects of LFU and microbubbles in combination with simvastatin, in inhibiting cell viability and promoting apoptosis of androgen-independent prostatic DU145 cells. Cultured DU145 cells were divided into six groups based on the combination of treatments as follows: Control, LFU, LFU and microbubbles (LFUM), simvastatin, LFU and simvastatin, LFUM and simvastatin. The cells were treated by LFU (80 kHz) continuously for 30 sec with an ultrasound intensity of 0.45 W/cm2 and a microbubble density of 20%. Simvastatin was added 30 h prior to the ultrasound exposure. The results indicated that cell viability was marginally reduced in the LFU and simvastatin alone treatment groups compared with the control 24 h following ultrasound exposure. The combination of LFU, with microbubbles or simvastatin, potentiated the growth inhibition; the greatest inhibition was observed in the cells that were subject to treatment with LFUM and simvastatin in combination. Furthermore, this inhibitory effect was enhanced in a time-dependent manner. For cell apoptosis, a low dose of simvastatin had no apparent affect on the DU145 cells, while LFU marginally promoted cell apoptosis. Microbubbles or simvastatin increased the apoptosis rate of the DU145 cells, however, the combination of LFUM and simvastatin induced a strong synergistic effect on cell apoptosis. Western blotting analysis demonstrated a high expression level of caveolin-1 in resting DU145 cells. LFUM or combined LFU and simvastatin resulted in a greater reduction in the expression compared with the control group (P<0.05). The expression of caveolin-1 was lowest in the LFUM combined with simvastatin treatment group. The expression of phospho-Akt (p-Akt) was consistent with caveolin-1, with the lowest expression levels of p-Akt observed in the cells that were treated with the combination of LFUM and simvastatin. The results indicate that LFUM in combination with simvastatin may additively or synergistically inhibit cell viability and induce apoptosis of DU145 cells by downregulating caveolin-1 and p-Akt protein expression.

Caveolin-1 as a biomarker to predict therapeutic effect of low-frequency ultrasound combined with SonoVue on prostate cancer in nude mice model.

BACKGROUND: Caveolin-1 is a major structural component of cell membrane invaginations. Over-expression of caveolin-1 is closely related to the tumorigenesis and progression of prostate cancer. Recently, contrast microbubbles in combination with ultrasound are being investigated for their therapeutic applications in tumor cells. However, the response of caveolin-1 after low-frequency ultrasound and SonoVue treatment in animal model is unclear. OBJECTIVE: The goal of this study was to evaluate the effect of 80 kHz ultrasound and/or SonoVue on caveolin-1 expression and secretion in DU145 prostate tumors in nude mice. METHODS: Six-week-old BALB/c male nude mice were subcutaneously injected with DU145 cells in the right flank to establish a prostate cancer model, which were randomly divided into four groups (n=8 each): control group (sham-ultrasound exposure), SonoVue group, 80 kHz ultrasound group, 80 kHz ultrasound combined with SonoVue group. Tumor volumes and wet weights were measured, and the tumor volume curve was obtained as well. The mice were euthanized 21 days after treatment. Specimens of the tumor tissues were assessed the expression of caveolin-1 by immunohistochemistry and Western blot. The serum concentrations of caveolin-1 were detected by ELISA. RESULTS: Treatment with ultrasound alone produced tumor volumes and weights reduction compared with control and SonoVue group. Combined ultrasound and SonoVue treatment produced greater tumor regression than either treatment alone (p < 0.05). Serum caveolin-1 concentrations were lower in the combination of ultrasound and SonoVue group than they were in control group (p =0.005), and had some certain correlation with tumor growth (wet weight) (r =0.507), although the difference was not statistically significant (p=0.199). Ultrasound alone treatment only slightly reduced the caveolin-1 concentrations in comparison with the control, and the difference was not statistically significant (p=0.125). The ultrasound-treated mice showed significant reduction in expression levels of caveolin-1 protein, compared with the control (p < 0.05). Levels of caveolin-1 were further reduced when combined with ultrasound and SonoVue as compared to the control (p < 0.01). CONCLUSIONS: Our results suggest that 80 kHz ultrasound have antitumor effect and the effect could be further strengthened by the combination of SonoVue. Down-regulating the expression of caveolin-1 is likely a potential biomarker of response to ultrasound and SonoVue treatment in prostate cancer mouse model.