Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.
Humans ; Fusobacterium nucleatum/metabolism* ; Mouth Neoplasms/metabolism* ; Disease Progression ; Proteomics ; Carcinoma, Squamous Cell/metabolism* ; Host-Pathogen Interactions ; Metabolic Networks and Pathways ; Case-Control Studies ; Mass Spectrometry

PURPOSE: To determine the accuracy of knee examination under anesthesia (EUA) and develop a prognostic score for partial anterior cruciate ligament (ACL) tears. MATERIALS AND METHODS: A total of 229 patients with an ACL injury were included. Knee EUA was performed using the Lachman test, pivot shift test and arthrometric maximum manual side-to-side difference (AMMD) test. The arthroscopic examination is the gold standard for the diagnosis of partial and complete ACL tears, which was compared with EUA findings. Multivariate logistic regression was estimated, and the significant variables were used to develop a predictive score. RESULTS: The relative risk for a complete tear with Lachman 2+ was 8.55 (range, 3.5 to 20.7) and 53.04 (range, 6.7 to 417) with Lachman 3+, compared to Lachman 1+. Negative pivot shift was reported in 23 cases in the partial tear group (76.7%) and in 22 in the complete tear group (11.1%). The AMMD was 3.5 mm in the partial tear group and 5.4 mm in the complete tear group (p < 0.05). A prognostic score of less than five suggested the presence of a partial ACL tear. The score showed 81.1% sensitivity and 68.7% specificity. CONCLUSIONS: Partial ACL tears can be differentiated from complete tears with Lachman test, pivot shift test, and AMMD test.
Anesthesia ; Anterior Cruciate Ligament ; Diagnosis ; Humans ; Knee ; Logistic Models ; Sensitivity and Specificity ; Tears