A depth-resolved quantitative evaluation method for non-carious cervical lesions treatment with optical coherence tomography.

OBJECTIVES: The aim of this study is prognostic assessment of surface smoothness and the presence of internal bubbles after treatment of non-cancerous cervical lesions (NCCLs) using optical coherence tomography (OCT). METHODS: After treatment with NCCLs, cross-sectional images of the lesion parts of the sample were non-invasively acquired and analyzed. The surface smoothness between tooth and resin, resin and cemento-enamel junction, and the presence bubble inside resin was confirmed. In addition, using an algorithm that distinguishes between resin and dental structure based on OCT cross-sectional images, we quantitatively analyzed the amount of resin used in treating NCCLs and acquired 3D images. RESULTS: The inner structure of the resin in each sample was checked, and the presence of bubbles was confirmed. In addition, the resin sections were separated from the tomographic images acquired by OCT to visualize 3D images. The volume of resin used in the treatment part of each NCCLs samples was quantitatively analyzed as 3.7216 ∼ 14.889 mm3. CONCLUSIONS: OCT is able to measure not only the surface abrasion provided by existing intraoral scanner, but also the size and depth location of interal bubbles, which is distinctive advantage of our method. Based on our results, OCT is a significant tool for qualitative and quantitative analysis of dental NCCLs treatment before and after treatment. CLINICAL SIGNIFICANCE: The study used OCT, a non-destructive diagnostic, to reveal the structure of the resin and the location and size of bubbles after NCCLs treatment. These findings could be golden standard in determining the prognosis of NCCLs treatment.

Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound.

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain. In this study, sonosensitive liposome encapsulating doxorubicin (DOX) was developed for enhancement of GBM penetration in combination with focused ultrasound (FUS) and microbubbles. Upon ultrasound (US) irradiation, microbubbles induce cavitation resulting in the tight junction of BBB endothelium to temporarily open. In addition, the composition of sonosensitive liposome was optimized by comparison of sonosensitivity and intracellular uptake to U87MG cells. The optimal sonosensitive liposome, IMP301-DC, resulted 123.9 ± 38.2 nm in size distribution and 98.2 % in loading efficiency. Related to sonosensitivity of IMP301-DC, US-triggered release ratio of doxorubicin was 69.2 ± 12.3 % at 92 W/cm2 of US intensity for 1 min. In the in vivo experiments, the accumulation of DiD fluorescence probe labeled IMP301-DC-shell in the brain through the BBB opening was increased more than two-fold compared to that of Doxil-shell, non-sonosensitive liposome. US exposure significantly increased GBM cytotoxicity of IMP301-DC. In conclusion, this study demonstrated that IMP301-DC could serve as an alternative solution to enhance the penetration to GBM treatment via BBB opening by non-invasive FUS combined with microbubbles.

Ultrasound-Responsive Liposomes for Targeted Drug Delivery Combined with Focused Ultrasound.

Chemotherapeutic drugs are traditionally used for the treatment of cancer. However, chemodrugs generally induce side effects and decrease anticancer effects due to indiscriminate diffusion and poor drug delivery. To overcome these limitations of chemotherapy, in this study, ultrasound-responsive liposomes were fabricated and used as drug carriers for delivering the anticancer drug doxorubicin, which was able to induce cancer cell death. The ultrasound-sensitive liposome demonstrated a size distribution of 81.94 nm, and the entrapment efficiency of doxorubicin was 97.1 ± 1.44%. The release of doxorubicin under the ultrasound irradiation was 60% on continuous wave and 50% by optimizing the focused ultrasound conditions. In vivo fluorescence live imaging was used to visualize the doxorubicin release in the MDA-MB-231 xenografted mouse, and it was demonstrated that liposomal drugs were released in response to ultrasound irradiation of the tissue. The combination of ultrasound and liposomes suppressed tumor growth over 56% more than liposomes without ultrasound exposure and 98% more than the control group. In conclusion, this study provides a potential alternative for overcoming the previous limitations of chemotherapeutics.

The efficacy of intraarticular viscosupplementation after arthroscopic partial meniscectomy: a randomized controlled trial.

BACKGROUND: This study aimed to evaluate the efficacy of viscosupplementation after arthroscopic partial meniscectomy. METHOD: A randomized controlled trial of 47 patients who underwent arthroscopic partial meniscectomy was conducted between March 2020 and March 2021. Patients were randomized into two groups: a viscosupplementation group (n = 23) and a control group (n = 24). A single-dose intraarticular hyaluronic acid injection was used as viscosupplementation. The 100 mm visual analogue scale (VAS) for pain assessment was measured at baseline and at 1 day, 2 weeks, 6 weeks, and 3 months post-surgery. The International Knee Documentation Committee (IKDC), Tegner, Lysholm, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores and range of motion (ROM) of the knee were measured at baseline, 2 weeks, 6 weeks, and 3 months. RESULTS: The 100 mm VAS score for pain was significantly lower in the viscosupplementation group at 2 weeks post-surgery (27.5 mm vs. 40.7 mm, P = 0.047). ROM was significantly greater in the viscosupplementation group than in the control group at 2 weeks (131.5° vs. 121.0°, P = 0.044) post-surgery. No significant differences were observed in the IKDC or in the Tegner, Lysholm, and WOMAC scores between the two groups. CONCLUSIONS: Viscosupplementation after arthroscopic partial meniscectomy significantly reduced pain at 2 weeks post-surgery and improved ROM of the knee at 2 weeks post-surgery. There might be some benefits in terms of pain and functional recovery of viscosupplementation after arthroscopic surgery. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. TRIAL REGISTRATION: This randomized controlled trial was registered at cris.nih.go.kr # KCT0004921 .

Combination Therapy with Doxorubicin-Loaded Reduced Albumin Nanoparticles and Focused Ultrasound in Mouse Breast Cancer Xenografts.

Because chemotherapeutic drugs are often associated with serious side effects, the central topic in modern drug delivery is maximizing the localization of drugs at the target while minimizing non-specific drug interactions at unwanted regions. To address this issue, biocompatible nanoparticles have been developed to enhance the drug half-life while minimizing the associated toxicity. Nevertheless, relying solely on the enhanced half-life and enhanced permeability and retention (EPR) effects has been ineffective, and designing stimulus-sensitive nanoparticles to introduce the precise control of drug release has been desired. In this paper, we introduce a pH-sensitive, reduced albumin nanoparticle in combination with focused ultrasound treatment. Not only did these nanoparticles have superior therapeutic efficacy and toxicity profiles when compared to the free drugs in xenograft mouse models, but we were also able to show that the albumin nanoparticles reported in this paper were more suitable than other types of non-reduced albumin nanoparticles as vehicles for drug delivery. As such, we believe that the albumin nanoparticles presented in this paper with desirable characteristics including the induction of strong anti-tumor response, precise control, and superior safety profiles hold strong potential for preclinical and clinical anticancer therapy.

Pro-Oxidant Drug-Loaded Au/ZnO Hybrid Nanoparticles for Cancer-Specific Chemo-Photodynamic Combination Therapy.

Photodynamic therapy (PDT) is a noninvasive therapeutic strategy involving photosensitizers and external light for the selective destruction of target tumors. Chemo-photodynamic combination therapy has attracted widespread attention to improve the outcome of cancer treatment by PDT only. In this study, light-triggered reactive oxygen species (ROS)-generating, polyethylene glycol (PEG)-coated zinc oxide nanorods (PEG-ZnO NRs) were synthesized and complexed with pro-oxidant piperlongumine (PL) to achieve cancer-targeted chemo-photodynamic combination therapy. It was found that PEG-ZnO NRs considerably increased intracellular ROS under UV light irradiation. The loading of PL to PEG-ZnO NRs further increased the intracellular ROS levels in MCF-7 human breast cancer cells due to efficient intracellular delivery of PL. As a result, PL-loaded PEG-ZnO NRs (PL-PEG-ZnO NRs) exhibited a synergistic anticancer activity under UV irradiation compared to free PL and PEG-ZnO NRs. PEG-ZnO NRs were further modified with Au NPs to enhance their capability of generating ROS under light. Au NP-coated PEG-ZnO NRs (Au/PEG-ZnO NRs) with UV irradiation showed higher ROS quantum yields as compared to PEG-ZnO NRs. As a result, PL-loaded Au/PEG-ZnO NRs (PL-Au/PEG-ZnO NRs) exhibited higher cytotoxicity than PL-PEG-ZnO NRs upon UV irradiation. Moreover, PL-Au/PEG-ZnO NRs showed cancer-specific cytotoxicity in MCF-7 cells due to the cancer-specific apoptosis induced by pro-oxidant PL. This study demonstrates that PL-Au/PEG-ZnO NRs have high potential for efficient and cancer-targeted chemo-photodynamic combination therapy.

Photo-triggered antibacterial and anticancer activities of zinc oxide nanoparticles.

ZnO nanoparticles (ZnO NPs) have gained more attention in recent years due to their ability to induce the generation of reactive oxygen species (ROS) under light irradiation. Photo-triggered ROS generation by ZnO NPs and the resulting phototoxicity in cells have found use in antibacterial and anticancer applications. This review highlights recent advances in the development of ZnO NPs and hybrid-type functionalized ZnO NPs for photo-triggered antibacterial and anticancer activities. In addition, various chemical modifications including metal doping, metal hybridization, modification with polymers, and sensitization by organic photosensitizers have been further introduced to enhance the photocatalytic efficiency and ROS generation capability of ZnO NPs. The enhanced ROS generation efficiency of modified ZnO NPs consequently increases their antibacterial and anticancer activities. Additionally, we offer some insights into the design and engineering of next-generation ZnO NPs for more effective antibacterial and anticancer applications.

Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis.

PURPOSE: Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer. METHODS: We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression. RESULTS: There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73). CONCLUSION: Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.