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Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) and its treatments often result in dysphagia, necessitating prolonged use of a nasogastric (NG) tube. NG tube removal rates in patients with OPSCC were compared between two strategies (induction chemotherapy followed by surgery versus induction chemotherapy followed by chemoradiation therapy). The outcomes related to swallowing function and NG tube dependence were shared with clinical physicians for guidance. Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC. [ABSTRACT FROM AUTHOR]

Around half of all patients with oral squamous cell carcinoma (OSCC) present with lymphatic metastasis, a strong predictor of poor survival. Improving survival rates depends on preventing the first step in the "invasion-metastasis cascade," epithelial-to-mesenchymal transition (EMT), and developing antilymphangiogenesis therapies that antagonize lymphatic metastasis. The extracellular matrix-related protein WISP-1 (WNT1-inducible signaling pathway protein-1) stimulates bone remodeling and tumor progression. We have previously reported that WISP-1 promotes OSCC cell migration and lymphangiogenesis induced by vascular endothelial growth factor C (VEGF-C). This investigation sought to determine the role of WISP-1 in regulating EMT in OSCC. Our analysis of oral cancer data from The Cancer Genome Atlas (TCGA) database revealed significant and positive associations between levels of WISP-1 expression and clinical disease stage, as well as regional lymph node metastasis. We also found higher levels of WISP-1 expression in serum samples obtained from patients with OSCC compared with samples from healthy controls. In a series of in vitro investigations, WISP-1 activated EMT signaling via the FAK/ILK/Akt and Snail signaling transduction pathways and downregulated miR-153-3p expression in OSCC cells. Our findings detail how WISP-1 promotes EMT via the miR-153-3p/Snail axis in OSCC cells. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV), a neurotropic flavivirus, annually causes over 30,000 Japanese Encephalitis (JE) cases in East and Southeast Asia. Histone deacetylases (HDACs) modulate lysine acetylation of histones and non-histone proteins, regulating many processes including inflammation and antiviral immune response. This study investigated antiviral activity of pan- and selective-HDAC inhibitors as host-targeting agents against JEV. Among HDAC inhibitors, selective HDAC6 inhibitors (tubastatin-A (TBSA) and tubacin) concentration-dependently inhibited JEV-induced cytopathic effect and apoptosis, as well as reduced virus yield in human cerebellar medulloblastoma cells. The 50% inhibitory concentration (IC50) values of virus yield was 0.26 μM for tubacin and 1.75 μM for TBSA, respectively. Tubacin (IC50 of 1.52 μM), but not TBSA, meaningfully blocked the production of intracellular infectious virus particles. In time-of-addition assays, the greatest potency of antiviral activity was observed in the mode of pre-treatment with tubacin (IC50 of 1.89 μM) compared to simultaneous (IC50 of 4.88 μM) and post-treatment (IC50 of 2.05 μM) modes. Interestingly, tubacin induced the hyperacetylation of a HDAC6 substrate Hsp90 and reduced the interaction of Hsp90 with JEV NS5 protein. Novobiocin, an Hsp90 inhibitor, diminished the NS5 protein amount and virus replication in JEV-infected cells. Meantime, tubacin suppressed the NS5 expression and antisense RNA genome synthesis in infected cells. Tubacin-induced Hsp90 hyperacetylation was suggested to influence the NS5 activity in JEV replication. Therefore, tubacin had a high potential of a host-targeting agent against JEV, exhibiting preventive and therapeutic activities against JEV infection.

γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC50 value of γ-bisabolene was 8.2 μM to TE671 cells. Cell cycle analysis with PI staining showed γ-bisabolene elevating the sub-G1 fractions in a time-dependent manner. In addition, annexin V-FITC/PI staining showed γ-bisabolene significantly triggering early (annexin-V positive/PI negative) and late (annexin-V positive/PI positive) apoptosis in dose-dependent manners. γ-Bisabolene induced caspase 3/8/9 activation, intracellular ROS increase, and mitochondrial membrane potential decrease in apoptosis of human neuro-blastoma cells. Moreover, γ-bisabolene increased p53 phosphorylation and up-regulated p53-mediated apoptotic genes Bim and PUMA, as well as decreased the mRNA and protein levels of CK2α. Notably, the results indicated the involvement of CK2α-p53 pathways in mitochondria-mediated apoptosis of human neuroblastoma cells treated with γ-bisabolene. This study elucidated the apoptosis induction pathways of γ-bisabolene-treated neuroblastoma cells, in which could be useful for developing anti-neuroblastoma drugs.