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The expression of programmed death ligand-1 (PD-L1) is controlled by complex mechanisms. The elucidation of the molecular mechanisms of PD-L1 expression is important for the exploration of new insights into PD-1 blockade therapy. Detailed mechanisms of the in situ expression of PD-L1 in tissues of oral squamous cell carcinomas (OSCCs) have not yet been clarified. We examined the mechanisms of PD-L1 expression focusing on the phosphorylation of downstream molecules of epidermal growth factor (EGF) and interferon gamma (IFN-γ) signaling in vitro and in vivo by immunoblotting and multi-fluorescence immunohistochemistry (MF-IHC), respectively. The in vitro experiments demonstrated that PD-L1 expression in OSCC cell lines is upregulated by EGF via the EGF receptor (EGFR)/PI3K/AKT pathway, the EGFR/STAT1 pathway, and the EGFR/MEK/ERK pathway, and by IFN-γ via the JAK2/STAT1 pathway. MF-IHC demonstrated that STAT1 and EGFR phosphorylation was frequently shown in PD-L1-positive cases and STAT1 phosphorylation was correlated with lymphocyte infiltration and EGFR phosphorylation. Moreover, the phosphorylation pattern of the related molecules in PD-L1-positive cells differed among the cases investigated. These findings indicate that PD-L1 expression mechanisms differ depending on the tissue environment and suggest that the examination of the tissue environment and molecular alterations of cancer cells affecting PD-L1 expression make it necessary for each patient to choose the appropriate combination drugs for PD-1 blockade cancer treatment.
The maxillofacial region of patients with facial asymmetry is deformed not only in the mandible but also in the maxilla, suggesting that the head region may also be deformed. Therefore, in this study, skeletally originated mandibular prognathism with facial asymmetry was evaluated in relation to cranial morphology. The cranial morphology of patients who visited the Chiba Dental Center of Tokyo Dental College and were diagnosed with skeletal mandibular prognathism with facial asymmetry (asymmetry group: ANB 0° or less; Menton deviation 4 mm or more; 30 subjects) and without facial asymmetry (symmetry group: ANB less than 0°; Menton deviation less than 3 mm) was measured and evaluated. As a method, the length and area of the cranium were measured using axial cephalometric radiographs. In the asymmetry group, there was a significant difference in the left–right difference in the long diameter of the posterior part of the cranium compared to the symmetry group (p = 0.009). The asymmetry group also had significant differences in the central and occipital areas of the cranium on the left and right sides compared to the symmetry group (p < 0.001). In the asymmetry group, the direction of Menton deviation and the direction of head region deviation coincided in about 70% of the cases. There was also a positive correlation between head deviation and the amount of Menton deviation. The results of this study suggested that patients with facial asymmetry had greater head deformity than patients without facial asymmetry.
Extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT) is a low‐grade B‐cell lymphoma. MALT lymphomas involving the sublingual gland are extremely rare. Herein, we report a case of MALT lymphoma of the sublingual gland. Additionally, we discuss challenging diagnostic aspects as well as current treatment strategies.
The hemorheological effect of ticlopidine was studied in rats ex vivo. Ticlopidine (30-300 mg/kg) was orally given to rats. Heparinized blood samples were taken from the carotid artery under pentobarbital anesthesia 3 hr after the drug administration for measurement of whole blood viscosity (ELD type cone-plate viscometer), micropore filtrability of red cells (Nuclepore membrane, 5 µm), erythrocyte sedimentation rate (ESR), hematocrit (Ht) and plasma fibrinogen. Red cell deformability was measured by counting the shear stressinduced cap-form cells under a scanning electronmicroscope. Mechanical flexibility of red cells was also studied by measuring hemolysis caused by turbulant flow.Ticlopidine treatment caused a significant decrease in whole blood viscosity (9.13 ± 0.15 and 6.17 ± 0.08 versus 9.80 ± 0.18 and 6.74 ± 0.09 Cp in control at 19.2 sec-1and 76.8 sec-1, respectively) and a significant increase in micropore filtrability of the red cells (0.54 ± 0.01 versus 0.40 ± 0.02 ml/min in control) without any changes in ESR, Ht and plasma fibrinogen. Ticlopidine also significantly stimulated the shear stress-induced shape change of the red cells to cap-form cells (12.08 ± 0.13 versus 8.66 ± 0.23 % in control) and prevented mechanical hemolysis caused by a turbulant flow (16.8 ± 1 . 6 versus 30.5 ± 2.5 % in control).In addition to the platelet aggregation inhibitory action the hemorheological action of this agent may be useful for improving microcirculation and protecting red cells from mechanical disruption by turbulant blood flow.Increase in the adenylate cyclase and Mg2+-activated adenosine triphosphatase activities in red cell membranes may be associated with the effect of ticlopidine to increase red cell deformability.
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