Paclitaxel liposomes (PTX-LIPO) are a clinically promising antineoplastic drug formulation for the treatment of various extracranial cancers, excluding glioblastoma. A main reason for this is the presence of the blood–brain barrier (BBB) or blood–tumor barrier (BTB), preventing liposomal drugs from crossing at a therapeutically meaningful level. Focused ultrasound (FUS) in conjunction with microbubbles (MBs) has been suggested in many studies to be an effective approach to increase the BBB or BTB permeability. In this study, we investigated the feasibility of enhancing the delivery of PTX-LIPO in intracranial glioblastoma-bearing nude mice using pulsed low-intensity FUS exposure in the presence of MBs. Our results showed that the delivery efficiency of PTX-LIPO could be effectively improved in terms of the penetration of both the BBB in vitro and BTB in vivo by pulsed FUS sonication with a 10 ms pulse length and 1 Hz pulse repetition frequency at 0.64 MPa peak-rarefactional pressure in the presence of MBs. Quantitative analysis showed that a 2-fold higher drug concentration had accumulated in the glioblastoma 3 h after FUS treatment, with 7.20±1.18 µg PTX per g glioma tissue. Longitudinal magnetic resonance imaging analysis illustrated that the intracranial glioblastoma progression in nude mice treated with PTX-LIPO delivered via FUS with MBs was suppressed consistently for 4 weeks compared to the untreated group. The medium survival time of these tumor-bearing nude mice was significantly prolonged by 20.8%, compared to the untreated nude mice. Immunohistochemical analysis further confirmed the antiproliferation effect and cell apoptosis induction. Our study demonstrated that noninvasive low-intensity FUS with MBs can be used as an effective approach to deliver PTX-LIPO in order to improve their chemotherapy efficacy toward glioblastoma.
Background Colorectal cancer (CRC) is one of the most common tumors among both men and women worldwide. The incidence and mortality of CRC remain a serious problem, especially in developed countries [1]. Traditional treatment options such as surgery, radiation therapy, and chemotherapy have severe side-effects, necessitating the development of novel treatment regimens for CRC [2].
Background
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver diseases. Ultrasound elastography has been used for the diagnosis of NAFLD. However, clinical research on steatosis by elastography technology has mainly focused on steatosis with fibrosis or non-alcoholic steatohepatitis (NASH), while steatosis without fibrosis has been poorly studied. Moreover, the relationship between liver viscoelasticity and steatosis grade is not clear. In this study, we evaluated the degree of liver steatosis in a simple steatosis rat model using shear wave elastography (SWE).
Results
The viscoelasticity values of 69 rats with hepatic steatosis were measured quantitatively by SWE in vivo and validated by a dynamic mechanical analysis (DMA) test. Pathological sections were used to determine the steatosis grade for each rat. The results showed that the elasticity values µ obtained by the two methods followed the same trend, and µ is significantly correlated with liver steatosis. The Pearson’s correlation coefficients indicate that $$\mu$$
μ
obtained by SWE is positively linear correlated with DMA (r = 0.628, p = 7.85 × 10–9). However, the viscosity values $$\eta$$
η
obtained by SWE were relatively independent of those obtained by DMA with a correlation coefficient of − 0.01. The combined Voigt elasticity measurements have high validity in the prediction of steatosis (S0 vs. S1–S4), with an AUROC of 0.755 (95% CI 0.6175–0.8925, p < 0.01) and the optimal cutoff value was 2.08 kPa with a sensitivity of 78% and specificity of 63%.
Conclusion
SWE might have the feasibility to be introduced as an auxiliary technique for NAFLD patients in clinical settings. However, the viscosity results measured by SWE and DMA are significantly different, because the two methods work in different frequency bands.
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