Clinico-pathological Spectrum of Oral Cavity Lesions at a Tertiary Care Center in Central Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Head and neck cancer is the sixth most common cancer in the world. The disease burden is increasing at an alarming rate in developing Southeast Asian countries. This study aims to report the histopathological spectrum of oral cavity lesions at a tertiary cancer center in central Nepal. METHODS: This study included all those cases of oral cavity lesions, of which diagnostic biopsy was done from January 2018 to December 2019. The data were retrieved from the Department of Pathology of BP Koirala Memorial Cancer Hospital. The study proposal was approved by the Institutional Review Committee at BPKMCH (Ref: 247/2020) on 28th June 2020. Convenience sampling was done. Data was analyzed using Statistical Package for the Social Sciences version 20 using descriptive statistics. RESULTS: A total of 851 cases of oral cavity lesions were included in this study. The mean age of the study population was 55.9 years, with male to female ratio of 3:1. Malignant lesions composed of 472 (55.5%) cases followed by premalignant lesion of 104 (12%). More than 453 (95%) malignant cases were squamous cell carcinoma, of which 342 (75%) were a well-differentiated type. The buccal cavity is the most common site of malignant lesion 212 (45%), followed by tongue 96 (20%) and lower gingivobuccal region 86 (18%). CONCLUSIONS: Malignant lesions are the most common histopathological findings in the oral cavity lesion with squamous cell carcinoma type. Oral cancer is common cancer that can be prevented and cured if detected early.

Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin protein degradation pathway: relevance for Parkinson's disease?

Parkinson's disease (PD) is characterized by the presence of proteinaceous neuronal inclusions called Lewy bodies in susceptible dopaminergic midbrain neurons. Inhibition of the ubiquitin-proteasome protein degradation pathway may contribute to protein build-up and subsequent cell death. Ubiquitin is normally activated for transfer to substrate proteins by interaction with the E1 ubiquitin ligase enzyme via a thiol ester bond. Parkinson's disease is also characterized by decreases in midbrain levels of total glutathione which could impact on E1 enzyme activity via oxidation of the active site sulfhydryl. We have demonstrated that increasing reductions in total glutathione in dopaminergic PC12 cells results in corresponding decreases in ubiquitin-protein conjugate levels suggesting that ubiquitination of proteins is inhibited in a glutathione-dependent fashion. Decreased ubiquitinated protein levels appears to be due to inhibition of E1 activity as demonstrated by reductions in endogenous E1-ubiquitin conjugate levels as well as decreases in the production of de novo E1-ubiquitin conjugates when glutathione is depleted. This is a reversible process as E1 activity increases upon glutathione restoration. Our data suggests that decreases in cellular glutathione in dopaminergic cells results in decreased E1 activity and subsequent disruption of the ubiquitin pathway. This may have implications for neuronal degeneration in PD.