HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

The Evaluation of Various Restoration Techniques on Internal Adaptation of Composites in Class V Cavities

Aim. The aim of this study was to evaluate the effect of different restoration techniques on the formation of internal microgaps between materials and dentin in class V restorations. Materials and Methods. Twenty-five extracted human premolars were prepared with standardized class V cavity outlines (3 mm × 2 mm × 2 mm). The cavities were randomly divided into 5 groups of 10 cavities each and restored according to manufacturer’s instructions: Group 1: preheating (55°C) conventional composite (Filtek Z250), Group 2: flowable composite (Filtek Flow), Group 3: Filtek Flow + Filtek Z250 light-cured separately, Group 4: Filtek Flow + Filtek Z250 light-cured simultaneously, and Group 5 (control): Filtek Z250 at room temperature (23°C). The specimens were then thermocycled and cross-sectioned through the center of the restoration. Subsequently, impressions were taken, and epoxy resin replicas were made. The internal adaptation of the materials to the axial wall was analyzed under SEM. Results. The preheated Filtek Z250 (Group 1) showed better internal adaptation than the room temperature groups (P<0.05). The combination of Filtek Flow with Filtek Z250 which was light-cured separately (Group 3) exhibited better internal adaptation than control group (P<0.05). Conclusion. Different restoration techniques exhibit different behavior regarding internal adaptation to dentin after photopolymerization

Damage detection in composites using nonlinear ultrasonically modulated thermography

This paper proposes a novel nonlinear ultrasonically stimulated thermography technique for a quick and reliable assessment of material damage in carbon fibre reinforced plastic (CFRP) composite materials. The proposed nondestructive evaluation (NDE) method requires narrow sweep ultrasonic excitation using contact piezoelectric transducers in order to identify dual excitation frequencies associated with the damage resonance. High-amplitude signals and higher harmonic generation are necessary conditions for an accurate identification of these two input frequencies. Dual periodic excitation using high- and low-frequency input signals was then performed in order to generate frictional heating at the crack location that was measured by an infrared (IR) camera. To validate this concept, an impact damaged CFRP composite panel was tested and the experimental results were compared with traditional flash thermography. A laser vibrometer was used to investigate the response of the material with dual frequency excitation. The proposed nonlinear ultrasonically modulated thermography successfully detected barely visible impact damage in CFRP composites. Hence, it can be considered as an alternative to traditional flash thermography and thermosonics by allowing repeatable detection of damage in composites