amyloid-beta-peptides and Neoplasms

Acrolein, a highly toxic α, β-unsaturated aldehyde, occurs as pollutant in the environment (e.g., tobacco smoke and exhaust gas) and is ubiquitously generated in biosystems (e.g., the lipid peroxidation process and metabolism of polyamine or amino acids). High accumulation of acrolein in biosystems is often linked pathologically with several oxidative stress-related diseases, including cancer and Alzheimer's disease. Accordingly, acrolein holds great potential as a key biomarker in oxidative stress-related diseases, and direct measurement of acrolein in biological samples is important to provide information for diagnostic and therapeutic purposes. Recently, we have serendipitously discovered the unrecognized reactivity of phenyl azide to acrolein. Phenyl azide can rapidly and selectively react with acrolein in a "click" manner to provide 4-formyl-1,2,3-triazoline through 1,3-dipolar cycloaddition. We have successfully utilized the acrolein-azide click reaction as a simple but robust method for detecting and visualizing acrolein generated by live cells in the context of oxidative stress processes. In addition, we also serendipitously discovered novel cycloaddition reactions of N-alkyl-α,β-unsaturated imines derived from acrolein and biogenic amines (e.g., polyamines, norepinephrine, and sphingosine), to yield 8-membered cyclic compounds. We then examined the biological functions of the cyclic products and revealed for the first time their roles in the oxidative stress mechanism and inhibition of amyloid β(1-40) fibrillization.

Topics: Acrolein; Alzheimer Disease; Amyloid beta-Peptides; Azides; Biogenic Amines; Biomarkers; Cycloaddition Reaction; Environmental Pollutants; Imines; Molecular Imaging; Neoplasms; Oxidative Stress; Peptide Fragments

Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer's disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aβ) levels with cancer remain largely unknown. In this case-control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD. Plasma levels of Aβ40, Aβ42, common pro-inflammatory cytokines, IL-1β, IL-6, TNF-α, IFN-γ, anti-inflammatory IL-4, chemokines, and cytokines MCP-1 were measured with enzyme-linked immunosorbent assay (ELISA) kits. Plasma levels of Aβ40 and Aβ42 in all cancer patients were higher than that in normal controls. More specifically, hepatic cancer patients exhibited significantly higher plasma Aβ levels. No significant difference in plasma Aβ levels was found between chemotherapy and no chemotherapy subgroups. Plasma Aβ levels were not significantly correlated with pro-inflammatory cytokines, anti-inflammatory, chemokines, and cytokines. Peripheral Aβ levels increased in cancer patients, especially in patients with hepatic cancer, independent of chemotherapy and inflammation. Further verification is required for the association between plasma Aβ and cancer.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antineoplastic Agents; Case-Control Studies; Chemokine CCL2; Chemokines; Female; Humans; Interferon-gamma; Interleukin-1beta; Interleukin-4; Interleukin-6; Male; Middle Aged; Neoplasms; Peptide Fragments; Tumor Necrosis Factor-alpha