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Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study is to assess whether short-term hypothyroidism could impair endothelial function in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels in patients at three time points: the day before thyroxine withdrawal (P1), the day before RAI administration (P2) and 4–6 weeks after RAI therapy (P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We defined the FMD(%) value decreasing by more than 1% as impaired value. We analyzed the changes of FMD, thyroid hormone and lipids at three time points. FMD (%) was impaired at P2 compared to P1 and was recovered at P3 after restoring LT4 therapy (P1 vs P2 vs P3, 8.05±1.55 vs 7.26±1.50 vs 7.79 ± 1.38, P = 0.438). Among all parameters, the change of LDL cholesterol (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1 − 2, r=-0.326, P = 0.020; P2 − 3, r=-0.306, P = 0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the same state before RAI therapy after restoring LT4 therapy.

Increasing data indicate that long noncoding RNA (lncRNA) DLEU2 is implicated in carcinogenesis in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and molecular mechanism by which lncRNA DLEU2 contributes to HCC remain unknown. The association of lncRNA DLEU2 with clinicopathological characteristics and prognosis in patients with HCC was analyzed by qRT-PCR, and public TCGA dataset. CCK-8, colony formation and Transwell assays were performed to verify the role of lncRNA DLEU2 in HCC. RNA immunoprecipitation (RIP), luciferase gene report and qRT-PCR assays were employed to uncover lncRNA DLEU2-spevific binding with miR-30a-5p. The effect of lncRNA DLEU2 and (or) miR-30a-5p on PTP4A1 expression was examined by Western blot analysis. As a consequence, we found that lncRNA DLEU2 was upregulated in HCC tissue samples and associated with distant metastasis and poor survival in patients with HCC. Knockdown of lncRNA DLEU2 impaired HCC cell proliferation, colony formation and invasion, but ectopic expression of lncRNA DLEU2 abolished these effects. Furthermore, lncRNA DLEU2 harbored a negative correlation and specific binding with miR-30a-5p in HCC cells. Knockdown of lncRNA DLEU2 upregulated miR-30a-5p, but downregulated its target PTP4A1, and miR-30a-5p abrogated lncRNA DLEU2-induced tumor-promoting effects and PTP4A1 upregulation. Taken together, our findings demonstrate that lncRNA DLEU2 promotes growth and invasion of HCC cells by regulating miR-30a-5p/ PTP4A1 axis.

Prostate cancer is a common type of cancer in elderly men. The aim of the present study was to evaluate the effects of ultrasound exposure in combination with SonoVue microbubbles on liposome-mediated transfection of wild-type P53 genes into human prostate cancer cells. PC-3 human prostate cancer cells were exposed to ultrasound; duty cycle was controlled at 20% (2 sec on, 8 sec off) for 5 min with and without SonoVue microbubble echo-contrast agent using a digital sonifier (frequency, 21 kHz; intensity, 46 mW/cm2). The cells were divided into eight groups, as follows: Group A (SonoVue + wild-type P53), group B (ultrasound + wild-type P53), group C (SonoVue + ultrasound + wild-type P53), group D (liposome + wild-type P53), group E (liposome + SonoVue + wild-type P53), group F (liposome + wild-type P53 + ultrasound), group G (liposome + wild-type P53 + ultrasound + SonoVue) and the control group (wild-type P53). Following treatment, a hemocytometer was used to measure cell lysis, reverse transcription-quantitative polymerase chain reaction and western blotting were performed to detect P53 gene transfection efficiency, Cell Counting Kit-8 was employed to reveal cell proliferation and Annexin V/propidium iodide staining was used to determine cell apoptosis. Cell lysis was minimal in each group. Wild-type P53 gene and protein expression were significantly increased in the PC-3 cells in group G compared with the control and all other groups (P

OBJECTIVE To study the clinical pathologic characteristics of β-catenin, Ki67 and Her-2/neu in gastric cancer and the correlation of β-catenin and Ki67 to the protein expression and gene conditions of Her-2/Neu. METHODS The protein expression of β-catenin, Ki67 and Her-2/Neu was detected by immunohistochemistry in 101 cases of gastric cancer and the gene conditions of Her-2/Neu by fluorescence in situ hybridization (FISH). RESULTS The protein expression of β-catenin, Ki67 and Her-2/Neu had close relationship with the clinical pathologic characteristics of gastric cancer. The β-catenin and Ki67 had obvious correlation to the differentiation, infiltration and lymphatic metastasis of the gastric cancer (P

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

The aim of the present study was to investigate the sonication effects of 21-kHz ultrasound (US) with microbubbles (MBs) on the subcutaneous prostate tumors of nude mice. In total, 15 tumor-bearing nude mice were divided into three groups: The control group, the low-frequency US group and the US+MB group. The MBs used were from US contrast agent SonoVue. The parameters of the US were as follows: 21 kHz, 26 mW/cm2 and a 40% duty cycle (2 sec on, 3 sec off) for 3 min, once every other day for 2 weeks. Color Doppler flow imaging, hematoxylin and eosin (HE) staining, immunoblotting and transmission electron microscopy (TEM) were used to evaluate the results. Following 2 weeks of treatment, the blood flow signal disappeared in the US+MB group only, and the tumor size was smaller when compared with the control and US groups. For the immunoblotting, the intensity of cyclooxygenase-2 and vascular endothelial growth factor in the US+MB group was lower compared with the other two groups. Tumor necrosis was present and the nucleus disappeared upon HE staining in the US+MB group. Upon TEM analysis, increased cytoplasmic vacuolation and dilatation of the perinuclear cisternae of the tumor cells were found in the US+MB group. In the control and US groups, the tumors had intact vascular endothelia and vessel lumens. However, lumen occlusion of the vessels was observed in the US+MB group. In conclusion, 21-kHz low-intensity US with MBs may result in vessel occlusion and growth inhibitory effects in the subcutaneous tumors of nude mice.

Benign prostatic hyperplasia is one of the most common conditions in middle-aged and elderly men. The aim of the study was to investigate the treatment effects of low-frequency ultrasound combined with a microbubbles agent on benign prostatic hyperplasia.Eighteen 7-year-old male beagles with prostatic hyperplasia were randomly divided into six groups (n=3): Control group, 21 kHz ultrasound group, 21 kHz ultrasound and microbubble contrast agent group, 1 MHz ultrasound group, 1 MHz ultrasound and microbubble contrast agent group, and microbubble contrast agent group. The histopathologic damage to prostate cells was assessed via transmission electron microscopy and optical microscopy. The protein expressions of prostate-specific antigen (PSA), inducible nitric oxide synthase (iNOS), and super oxidase dimutase (SOD) were detected by enzyme-linked immunosorbent assay. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) were detected by the Biochemistry Automatic Analyzer.Significant tissue injury, mitochondria injury, and cell apoptosis were observed in 21 kHz ultrasound and the microbubble contrast agent group. Compared with the control and microbubbles contrast agent groups, the decrease in levels of PSA or increase in levels of iNOs and SOD in the other four groups were statistically significant (P0.05). The lowest level of PSA and the highest levels of iNOs and SOD were observed in the 21 kHz ultrasound and microbubbles contrast agent group. No significant changes in levels of AST, ALT, BUN, and Cr were observed between the six groups.Our results suggest that lower frequency ultrasound may have a better effect on benign prostatic hyperplasia, and microbubble contrast agent application further strengthens this biological effect.

Combination therapy is used to optimize anticancer efficacy and reduce the toxicity and side-effects of drugs upon systemic administration. Ultrasound (US) combined with micro-bubbles (UM) enhances the intracellular uptake of cytotoxic drugs by tumor cells, particularly drug-resistant cells. In the present study, low-frequency and low-energy US (US irradiation conditions: frequency, 21 kHz; power density, 0.113 W/cm2; exposure time, 2 min at a duty cycle of 70%; and valid treatment time, 84 sec) were used in combination with microbubbles (100 μl/ml) to deliver mitoxantrone HCl (MIT) to DU145 cells. The results showed that UM did not change the cell viability in the short- or long-term. However, UM statistically enhanced the therapeutic effects and up to 31.26±3.34% of the cells exposed to UM were permeabilized compared with 9.74±2.55% of cells in the control, when using calcein (MW, 622.53) as a fluorogenic marker. Notably, UM affected the migration capability of the DU145 cells at 6 h post-treatment. In conclusion, the ultrasonic parameters used in the present study enhanced the chemotherapeutic effect and reduced the unwanted side-effects of MIT.

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 (200 μL 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-3 cells 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

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.

Ultrasound can be used not only in the examination, but also in the therapy, especially in the therapy of cancer, which has got effect in the treatment. Sonodynamic therapy is an experimental cancer therapy which uses ultrasound to enhance the cytotoxic effects of drugs 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 the cell membranes permeability, thereby allowing the delivery of exogenous molecules into the cells in some degree. Ultrasound could inhibit the proliferation or induce the apoptosis of the cancer cell in vitro or in vivo. Recent research indicated low frequency and low intensity ultrasound could induce cells apoptosis, and which could be strengthened by sonodynamic sensitivities, microbubbles, chemotherapeutic drugs and so on. Most kinds of ultrasound suppressed the proliferation of cancer cell through inducing the apoptosis of cancer cell. The mechanism of apoptosis is not clear. In this review, we will focus on and discuss the mechanisms of the induction of the apoptosis of cancer cell by ultrasound.