Oral cavity cancer is common worldwide. Furthermore, the epidermal growth factor receptor (EGFR) signaling pathway is considered to be constitutively activated in oral cancers. Paclitaxel is widely accepted as an antitumor drug as it effectively inhibits the cell cycle. This study predominantly explores the possible molecule mechanism of paclitaxel on oral cancer treatment. Cell viability was first detected using an MTT assay. Cell apoptosis was examined by Hoechst staining and flow cytometry using an annexin-V and propidium iodide kit. Specific EGFR signaling pathways were further explored through western blot analysis. Abnormal protein expression levels were determined via immunofluoresence. Additionally, the protein levels of matrix metalloproteinase (MMP)-2 and 9 were determined using ELISA. Paclitaxel significantly inhibited oral cancer cell viability in a time- and dose-dependent manner. Paclitaxel also enhanced oral cancer cell apoptosis via increased Bim and Bid protein expression. Furthermore, paclitaxel was observed to inhibit oral cancer cell proliferation through increased MMP-2 and MMP-9 protein levels. Paclitaxel inhibited the growth of the oral cancer cell line, tea8113 malignant proliferation and enhanced tea8113 cell apoptosis through inhibiting the EGFR signaling pathway.
Background SKV-012 is a novel engineered oncolytic virus (containing the viral neurovirulence ICP34.5 gene transcribed by the Survivin promoter with an upstream genetic component of interleukin-12 (IL-12) driven by the cytomegalovirus promoter) that preferentially replicates in tumors and helps stimulate antitumor immune responses.Methods We evaluated SKV-012’s safety and efficacy in preclinical models. In a phase I trial, patients with advanced solid tumors received intratumoral injections of escalating doses of SKV-012. Primary endpoints were safety and tolerability, while secondary endpoints were antitumor response and changes in the tumor microenvironment (TME), assessed by RECIST v1.1 criteria and multiplex immunohistochemistry and single-cell transcriptome analysis.Results SKV-012-infected tumor cells secreted high levels of IL-12 and exhibited increased ICP34.5 expression. The combination of oncolytic herpesvirus and IL-12 was proven to reshape the TME by increasing the infiltration of immune cells, thereby significantly inducing immune cell-mediated cytolysis of tumor cells both in vitro and in animal models. Based on this, we then tested the safety, efficacy and immunogenicity of SKV-012 in patients with advanced solid cancers in a phase I clinical trial (NCT06080984). No dose-limiting toxicities were observed, and adverse events were mild. Three patients achieved partial responses; one had stable disease and two had progressive disease. SKV-012 altered the TME, increasing CD8+ T cells, conventional dendritic cells, and programmed death-ligand 1 expression.Conclusions Intratumoral SKV-012 injections demonstrated a favorable safety profile and promising efficacy in animal models and patients with advanced cancers, thereby implicating its potential for clinical application in treatment-resistant advanced solid tumors.
To investigate the diagnostic value of combined multi-timepoint salivary pepsin testing (MTPSPT) and hypopharyngeal–esophageal multichannel intraluminal impedance–pH monitoring (HEMII–pH) for laryngopharyngeal reflux (LPR) and whether an appropriate reduction in the duration of HEMII–pH would affect the accuracy of diagnosis of LPR. Recruited patients were studied with both MTPSPT and HEMII–pH. The diagnosis of LPR was based on the occurrence of > 1 reflux event and/or positive results on any of the MTPSPT. The diagnostic value of combined diagnosis was studied through combining a breakdown of the 24-h HEMII–pH finding and the results of the MTPSPT. The diagnostic value was expressed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Based on 24-h HEMII–pH and MTPSPT, the positive rate of LPR was 83.33% and 74.69%, respectively. According to the combined diagnosis, the positive rate of LPR was 90.74%. The sensitivity and specificity of the combined diagnosis both were 89.51% and 100%, when the HEMII–pH intervals were 7 a.m.–6 p.m. and 7 a.m.–7 p.m., respectively. However, when the monitoring time was extended to 8 p.m. and bedtime, the sensitivity, specificity, PPV and NPV of the combined diagnosis both were 100%. The combination of MTPSPT and HEMII–pH increased the sensitivity and accuracy of diagnosis of LPR. For patients with positive MTPSPT results, the duration of HEMII–pH can be appropriately shortened to reduce patient sufferings.
