Lung cancer is a leading cause of cancer-related deaths worldwide, with less than a 5-year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over-expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non-small-cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti-EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her-2, and EGFR expression by treatments was measured by qRT-PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.
Whooping cough is a relatively new infectious disease afflicting human beings, compared with other infectious diseases, and is undergoing a resurgence despite decades of vaccination. The oldest known epidemic is thought to be the Paris outbreak of 1578. In this Historical Review, we describe three epidemics of whooping cough in Persia, which although arising roughly one century before the Paris outbreak, have not been examined in detail. A great amount of epidemiological detail was reported that not only distinguishes the various stages and complications of whooping cough, but also reveals unique immunological aspects of this disease. The first of these epidemics is the oldest recorded whooping cough epidemic. On the basis of epidemiological features, we propose that this whooping cough epidemic was the first to have taken place in Persia and might have been part of the first pandemic. This theory pushes back the date of first documented emergence of whooping cough by almost a century, which matches molecular data about its spread. Here, we discuss features of these early epidemics in relation to their initial emergence, potential origins, and spread to Europe.
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