Quadruplex-forming oligonucleotide targeted to the VEGF promoter inhibits growth of non-small cell lung cancer cells.

Background: Vascular endothelial growth factor (VEGF) is commonly overexpressed in a variety of tumor types including lung cancer. As a key regulator of angiogenesis, it promotes tumor survival, growth, and metastasis through the activation of the downstream protein kinase B (AKT) and extracellular signal-regulated kinase (ERK 1/2) activation. The VEGF promoter contains a 36 bp guanine-rich sequence (VEGFq) which is capable of forming quadruplex (four-stranded) DNA.

Genomic c-Myc quadruplex DNA selectively kills leukemia.

c-Myc, a key regulator of cell cycle and proliferation, is commonly overexpressed in leukemia and associated with poor prognosis. Conventional antisense oligonucleotides targeting c-myc may attenuate leukemic cell growth, however, are poorly taken into cells, rapidly degraded, and have unwanted effects on normal cells. The c-myc promoter contains a guanine-rich sequence (PU27) capable of forming quadruplex (four-stranded) DNA, which may negatively regulate c-myc transcription.

Hypoxia induces differential translation of enolase/MBP-1.

Background: Hypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The alpha-enolase gene encodes both a glycolytic enzyme (alpha-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent alpha-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia.

Differential effects of nitric oxide synthesis on pulmonary vascular function during lung ischemia-reperfusion injury.

Lung ischemia-reperfusion (IR) injury causes alveolar, epithelial and endothelial cell dysfunction which often results in decreased alveolar perfusion, characteristic of an acute respiratory distress syndrome. Nitric oxide (NO) from endothelium-derived NO synthase (eNOS) helps maintain a low pulmonary vascular resistance. Paradoxically, during acute lung injury, overproduction of NO via inducible NO synthase (iNOS) and oxidative stress lead to reactive oxygen and nitrogen species (ROS and RNS) formation and vascular dysfunction.

c-myc promoter binding protein regulates the cellular response to an altered glucose concentration.

Alpha-enolase is a bifunctional gene encoding both a glycolytic enzyme and a DNA binding protein, c-myc binding protein (MBP-1). MBP-1 binds the c-myc promoter and downregulates c-myc transcription. Since these alpha-enolase gene products have important functions in glucose metabolism and growth regulation, this gene may play a central role in regulating the abnormal proliferative characteristics of transformed cells.

Lung ischemia-reperfusion injury: implications of oxidative stress and platelet-arteriolar wall interactions.

Pulmonary ischemia-reperfusion (IR) injury may result from trauma, atherosclerosis, pulmonary embolism, pulmonary thrombosis and surgical procedures such as cardiopulmonary bypass and lung transplantation. IR injury induces oxidative stress characterized by formation of reactive oxygen (ROS) and reactive nitrogen species (RNS). Nitric oxide (NO) overproduction via inducible nitric oxide synthase (iNOS) is an important component in the pathogenesis of IR.

Mechanisms of homocysteine-induced oxidative stress.

Hyperhomocysteinemia decreases vascular reactivity and is associated with cardiovascular morbidity and mortality. However, pathogenic mechanisms that increase oxidative stress by homocysteine (Hcy) are unsubstantiated. The aim of this study was to examine the molecular mechanism by which Hcy triggers oxidative stress and reduces bioavailability of nitric oxide (NO) in cardiac microvascular endothelial cells (MVEC).

Inhibition of inducible nitric oxide synthase attenuates platelet adhesion in subpleural arterioles caused by lung ischemia-reperfusion in rabbits.

Oxidative stress, induced by lung ischemia-reperfusion, leads to platelet and leukocyte activation and may contribute to decreased alveolar perfusion by platelet adhesion to the arteriolar wall. We investigated the hypothesis that ischemia-reperfusion injury increases inducible nitric oxide synthase (iNOS) activity and subsequent generation of reactive nitrogen species with P-selectin-dependent platelet-endothelial interactions and vasoconstriction during lung reperfusion. Subpleural arterioles, labeled platelets, and leukocytes were examined in anesthetized, open-chest rabbits by intravital fluorescence microscopy.