Nanoparticle-enhanced PD-1/PD-L1 targeted combination therapy for triple negative breast cancer.

Breast cancer with triple-negative subtype (TNBC) presents significant challenges with limited treatment options and a poorer prognosis than others. While PD-1/PD-L1 checkpoint inhibitors have shown promise, their efficacy in TNBC remains constrained. In recent years, nanoparticle (NP) technologies offer a novel approach to enhance cancer therapy by optimizing the tumor microenvironment and augmenting chemo- and immunotherapy effects in various preclinical and clinical settings. This review discusses recent investigations in NP strategies for improving PD-1/PD-L1 blockade-based combination therapy for TNBC. Those include single or multi-therapeutic NPs designed to enhance immunogenicity of the tumor, induce immunogenic cell death, and target immunosuppressive elements within the tumor microenvironment. The investigations also include NPs co-loaded with PD-L1 inhibitors and other therapeutic agents, leveraging targeted delivery and synergistic effects to maximize efficacy while minimizing systemic toxicity. Overall, NP approaches represent a promising avenue for enhancing PD-1/PD-L1 checkpoint blockade-based combination therapy in TNBC and encourage further developmental studies.

Harnessing Nuclear Energy to Gold Nanoparticles for the Concurrent Chemoradiotherapy of Glioblastoma.

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6-146 nm), and a particular portion of 197Au atoms is simultaneously converted to 198Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ.

Predictive Value of Clinicopathological Factors to Guide Post-Operative Radiotherapy in Completely Resected pN2-Stage III Non-Small Cell Lung Cancer.

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC). Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome. Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1-3 positive lymph nodes, and a positive-to-dissected lymph node ratio ≤0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment.

The new X-ray/visible microscopy MAXWELL technique for fast three-dimensional nanoimaging with isotropic resolution.

Microscopy by Achromatic X-rays With Emission of Laminar Light (MAXWELL) is a new X-ray/visible technique with attractive characteristics including isotropic resolution in all directions, large-volume imaging and high throughput. An ultrathin, laminar X-ray beam produced by a Wolter type I mirror irradiates the sample stimulating the emission of visible light by scintillating nanoparticles, captured by an optical system. Three-dimensional (3D) images are obtained by scanning the specimen with respect to the laminar beam. We implemented and tested the technique with a high-brightness undulator at SPring-8, demonstrating its validity for a variety of specimens. This work was performed under the Synchrotrons for Neuroscience-an Asia-Pacific Strategic Enterprise (SYNAPSE) collaboration.

Biomechanical behavior of cavity design on teeth restored using ceramic inlays: An approach based on three-dimensional finite element analysis and ultrahigh-speed camera.

Ceramic fracture and debonding are the primary failures that follow ceramic inlay and can lead to stress and tooth fracture. In this study, we examined two designs-concave and flat-of the gingival cavity bottom for tooth cavities restored using ceramic inlays. We investigated the biomechanical behavior of ceramic inlay-restored teeth (concave and flat) through three-dimensional finite element analysis (FEA) and experimentally validated the results using an ultrahigh-speed camera. We conducted in vitro real-time recording of the deformation of a restored tooth during loading using an ultrahigh-speed camera. This technique enables further image registration to observe deformation variation and vector fields. The deformation vector fields revealed that the concave design moved the deformation toward the buccal side of the cavity bottom, whereas the flat design moved it toward the palatal side. These findings correlated with the FEA results, which indicated that the concave design constrained stress in the dentin cavity and relieved palatal stress. Our results suggest that incorporating a concave design in cavity preparation can improve the fracture resistance of ceramic inlay-restored teeth, preventing unrestorable fractures. The current study is the first to utilize an ultrahigh-speed camera in dental biomechanics, and such cameras are useful for nondestructive and dynamic analysis. STATEMENT OF SIGNIFICANCE: First utilize ultrahigh-speed cameras in dental biomechanics analysis. Tooth fracture videos captured by ultrahigh-speed camera helps us learn fracture mechanics in between tooth cavity design and ceramic inlay. Concave design leads to stress in safer areas that causes a less damaging fracture. Minimal invasive preparation by concave design strengthens tooth fracture resistance. Non-destructive data from ultrahigh-speed cameras combined with FEA can get more insight into how the stress and strain derived in biomaterials.

Ultrasound temperature estimation based on probability variation of backscatter data.

PURPOSE: In recent years, ultrasound imaging has become an attractive modality for noninvasive temperature monitoring. Temperature variations that occur during tissue heating could induce changes in various acoustic parameters that may affect the echo interference so as to make ultrasound backscattering a random process. In this study, we assumed that the degree of variation in the probability distribution of the backscattered signals is temperature dependent. The feasibility of using the variation in the backscatter statistics for ultrasound temperature estimation was investigated in this study. METHODS: We tested this hypothesis by carrying out experiments on agar phantoms and tissue samples using a temperature-regulated water tank and a microwave ablation system. During heating, raw images of the backscattered-signal envelope of each phantom and tissue at temperatures ranging between 37 °C and 45 °C were acquired to construct the parametric matrix based on the ratio of the change in the Nakagami parameter (RCN), which was used as a quantitative measure of the backscatter statistics. The absolute value of the RCN (ARCN) matrix was obtained, to which a polynomial approximation was applied to obtain the ARCN(pa) image. RESULTS: The results showed that the RCN matrix locally increased or decreased with increasing temperature, indicating bidirectional changes in the backscatter statistics. We also found that the ARCN significantly increased with the temperature, demonstrating that the magnitude of the variation in the probability distribution of the backscattered-signal envelope is a monotonic function of temperature. Unlike the phantom, tissues tended to exhibit a nonlinear dependency of the ARCN on the temperature that may be attributable to tissue denaturation. Especially, the ARCN(pa) image is highly suitable for visualizing the contour of the temperature distribution during microwave ablation of tissue samples. CONCLUSIONS: This study has demonstrated that temperature changes are reflected in variations in the envelope statistics. This novel approach makes it possible to develop an ultrasound temperature imaging method for simultaneously estimating the thermal dose and the tissue properties.

Using ultrasound CBE imaging without echo shift compensation for temperature estimation.

Clinical trials have demonstrated that hyperthermia improves cancer treatments. Previous studies developed ultrasound temperature imaging methods, based on the changes in backscattered energy (CBE), to monitor temperature variations during hyperthermia. Echo shift, induced by increasing temperature, contaminates the CBE image, and its tracking and compensation should normally ensure that estimations of CBE at each pixel are correct. To obtain a simplified algorithm that would allow real-time computation of CBE images, this study evaluated the usefulness of CBE imaging without echo shift compensation in detecting distributions in temperature. Experiments on phantoms, using different scatterer concentrations, and porcine livers were conducted to acquire raw backscattered data at temperatures ranging from 37°C to 45°C. Tissue samples of pork tenderloin were ablated in vitro by microwave irradiation to evaluate the feasibility of using the CBE image without compensation to monitor tissue ablation. CBE image construction was based on a ratio map obtained from the envelope image divided by the reference envelope image at 37°C. The experimental results demonstrated that the CBE image obtained without echo shift compensation has the ability to estimate temperature variations induced during uniform heating or tissue ablation. The magnitude of the CBE as a function of temperature obtained without compensation is stronger than that with compensation, implying that the CBE image without compensation has a better sensitivity to detect temperature. These findings suggest that echo shift tracking and compensation may be unnecessary in practice, thus simplifying the algorithm required to implement real-time CBE imaging.