Particulate matter in COPD pathogenesis: an overview.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder with substantial patient burden and leading cause of death globally. Cigarette smoke remains to be the most recognised causative factor behind COPD pathogenesis. Given the alarming increase in prevalence of COPD amongst non-smokers in recent past, a potential role of air pollution particularly particulate matter (PM) in COPD development has gained much attention of the scientists. Indeed, several epidemiological studies indicate strong correlation between airborne PM and COPD incidence/exacerbations. PM-induced oxidative stress seems to be the major player in orchestrating COPD inflammatory cycle but the exact molecular mechanism(s) behind such a process are still poorly understood. This may be due to the complexity of multiple molecular pathways involved. Oxidative stress-linked mitochondrial dysfunction and autophagy have also gained importance and have been the focus of recent studies regarding COPD pathogenesis. Accordingly, the present review is aimed at understanding the key molecular players behind PM-mediated COPD pathogenesis through analysis of various experimental studies supported by epidemiological data to identify relevant preventive/therapeutic targets in the area.

Genomic instability detected from the saliva of Head and Neck Squamous Cell Carcinoma patients: Association with clinical implications.

OBJECTIVES: Genomic instability in cancers is often associated with poor disease outcomes. In Head and Neck Squamous Cell Carcinoma (HNSCC), saliva being the contact fluid contains cancers cells shed from the primary tumour. This study detected genomic instability from cancer cells shed in saliva and correlated the same with clinical implications. DESIGN: Genomic instability in HNSCC patients (n = 81) was analysed and compared with control subjects (n = 30). Alu sequences were amplified from the DNA of the cells shed in saliva and from the blood (Germline DNA) using Alu-PCR. Band variations between amplified products of salivary cells' DNA and germline DNA were compared. 'Instability Score' was calculated by counting the band variation(s). The 'Instability Score' was further used as a measure of genomic instability. RESULTS: Higher instability was detected in patients as compared to the controls (p < 0.0001). After treatment, there was a significant decrease (p < 0.0001) in the Instability score and patients with higher instability scores responded better to radiotherapy. The patient group consuming both tobacco and alcohol had a higher instability score in comparison to the tobacco group (p = 0.0056). Also, Instability scores are inversely correlated with nodal metastasis (p = 0.0075). A high Instability score before treatment resulted in a better prognosis in HNSCC patients (HR: 1.8, 95%CI: 1.024-3.164, p = 0.0306). CONCLUSION: Our data suggest that genomic instability estimated from the tumour cells shed in the saliva of HNSCC patients by amplifying Alu sequence (Alu-PCR) is associated with radiotherapy response.