Characterization of pneumonia and other factors leading to poorer survival across all age groups in patients with non-small cell lung cancer (NSCLC).

Background: Lung cancer death rates and incidence in both men and women have decreased over the past two decades. However, certain subsets of non-small cell lung cancer (NSCLC) have arisen with poor outcomes. Identifying factors which contribute to poorer outcomes as well as those that inform early detection strategies remain unmet needs.

Cyclin-dependent kinase inhibitors for the treatment of lung cancer.

Introduction: Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression in both normal and malignant cells, functioning through complex molecular interactions. Deregulation of CDK-dependent pathways is commonly found in both non-small cell and small cell lung cancer, and these derangements suggest vulnerabilities that can be exploited for clinical benefit.

Areas Covered: In this review, the authors present an overview of the biology of CDKs in normal and malignant cells, with a focus on lung cancer, followed by an assessment of preclinical work that has demonstrated the vital role of CDKs in lung cancer development and progression, and the activity of CDK inhibitors in a variety of lung cancer models.

Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS.

Senescence is a potential tumor-suppressing mechanism and a commonly used model of cellular aging. One current hypothesis to explain senescence, based in part on the correlation of oxygen with senescence, postulates that it is caused by oxidative damage from reactive oxygen species (ROS). Here, we further test this theory by determining the mechanisms of hyperoxia-induced senescence.

Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors.

Mutations of the human type Ialpha regulatory subunit (RIalpha) of cyclic AMP-dependent protein kinase (PKA; PRKAR1A) lead to altered kinase activity, primary pigmented nodular adrenocortical disease, and tumors of the thyroid and other tissues. To bypass the early embryonic lethality of Prkar1a(-/-) mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline-responsive promoter. Down-regulation of Prkar1a by up to 70% was achieved in transgenic mouse tissues and embryonic fibroblasts, with concomitant changes in kinase activity and increased cell proliferation, respectively.