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

Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that prescription and non-prescription drugs, herbal and dietary supplements can cause to the liver. iDILI remains a major public health problem and a major cause of drug attrition. Given the lack of biomarkers for iDILI prediction, diagnosis and prognosis, searching new models to predict and study mechanisms of iDILI is necessary. One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI. Thus, major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients. However, there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms. Therefore, there is a need to optimize preclinical human

PURPOSE OF THE STUDY: Basal cell carcinoma (BCC) remains as the most common cutaneous neoplasm in the Philippines consisting of more than 60% of all skin cancers. Anacardium occidentale (Linn.) cashew extract, which had been used successfully in the removal of warts and moles in previous studies, is presented as a therapeutic option in BCC.
METHODS: An open-label prospective study was conducted on 36 patients (mean age of 65 years) with documented BCC lesions on middle third of the face. Cashew nut extract (DeBCC) application was offered to these patients as an alternative option to very unacceptable extirpative surgery offered by general and plastic surgeons as treatment for their lesions. Lesion size ranged from 7.5- 64 mm. (26.26 mm). Topical treatment was applied every 1-2 weeks, as needed. Follow-up examinations with photographic documentation were made every week to evaluate success of the treatment.
RESULTS: After a mean of 7 treatment applications (range of 1-20) all the lesions were undetectable on clinical examinations. Mild tingling sensation, which was reported by all patients during the treatment applications, was tolerable on all occasions. With follow-up ranging from 5-60 months (38.72 months), 16 patients completed the planned 5 - year post-treatment follow-up period. There were no recurrences detected.
CONCLUSIONS: Anacardium occidentale (Linn.) cashew extract (DeBCC) presents a viable and acceptable treatment option in primary BCC. The importance of this treatment option could be stressed in patients with lesions not amenable to the prescribed wide margin of resection needed in surgery.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Young Adult ; Aged ; Anacardium ; Carcinoma, Basal Cell ; Humans ; Moles ; Neoplasm Recurrence, Local ; Nevus ; Nevus, Pigmented ; Nuts ; Philippines ; Prospective Studies ; Recurrence ; Sensation ; Skin Neoplasms ; Surgeons ; Warts ;