The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.

Characterized as a chronic inflammatory disease of the large arteries, atherosclerosis is the primary cause of cardiovascular disease, the leading contributor of morbidity and mortality worldwide. Elevated plasma cholesterol levels and chronic inflammation within the arterial plaque are major mediators of plaque initiation, progression, and instability. In 2003, the protein PCSK9 (proprotein convertase subtilisin/kexin 9) was discovered to play a critical role in cholesterol regulation, thus becoming a key player in the mechanisms behind atherosclerotic plaque development. Emerging evidence suggests that PCSK9 could potentially have effects on atherosclerosis that are independent of cholesterol levels. The objective of this review was to discuss the role on PCSK9 in oxidation, inflammation, and atherosclerosis. This function activates proinflammatory cytokine production and affects oxidative modifications within atherosclerotic lesions, revealing its more significant role in atherosclerosis. Although a variety of evidence demonstrates that PCSK9 plays a role in atherosclerotic inflammation, the direct mechanism of involvement is still unknown, driving a gap in knowledge to such a predominant player in cardiovascular disease. Investigation of proteins structurally related to PCSK9 may interestingly be the link in unveiling the mechanistic role of this protein’s involvement in oxidation and inflammation. Importantly, the unique structure of PCSK9 bears structural homology to a one‐of‐a‐kind domain found in the metabolic protein resistin, which is responsible for many of the same inflammatory outcomes as PCSK9. Closing this gap in knowledge of PCSK9`s role in atherosclerotic oxidation and inflammation will provide fundamental information for understanding, preventing, and treating cardiovascular disease.

Cigarette smoking is the most important avoidable cardiovascular risk factor. It causes endothelial dysfunction and atherosclerosis and increases the risk of its severe clinical complications like coronary artery disease, myocardial infarction, stroke, and peripheral artery disease. Several next-generation tobacco and nicotine products have been developed to decrease some of the deleterious effects of regular tobacco smoking. This review article summarizes recent findings about the impact of cigarette smoking and next-generation tobacco and nicotine products on endothelial dysfunction. Both cigarette smoking and next-generation tobacco products lead to impaired endothelial function. Molecular mechanisms of endothelial dysfunction like oxidative stress, reduced nitric oxide availability, inflammation, increased monocyte adhesion, and cytotoxic effects of cigarette smoke and next-generation tobacco and nicotine products are highlighted. The potential impact of short- and long-term exposure to next-generation tobacco and nicotine products on the development of endothelial dysfunction and its clinical implications for cardiovascular diseases are discussed.