Molecular basis of carcinogenesis in diabetic patients (Review)

Matyszewski,Artur; Czarnecka,Anna M.; Solarek,Wojciech; Korzeń,Piotr; Safir,Ilan J.; Kukwa,Wojciech; Szczylik,Cezary

doi:10.3892/ijo.2015.2865

Molecular basis of carcinogenesis in diabetic patients (Review)

Authors:
- Artur Matyszewski
- Anna M. Czarnecka
- Wojciech Solarek
- Piotr Korzeń
- Ilan J. Safir
- Wojciech Kukwa
- Cezary Szczylik
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Affiliations: Department of Oncology, Military Institute of Medicine, Warsaw, Poland, Department of Urology, Emory University School of Medicine, Atlanta, GA, USA, Department of Otolaryngology, Medical University of Warsaw, Warsaw, Poland
Published online on: February 3, 2015 https://doi.org/10.3892/ijo.2015.2865
Pages: 1435-1443

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Abstract

The most important molecular mechanisms promoting carcinogenesis in patients with diabetes mellitus (DM) include oxidative stress, excessive generation of free radicals and nitrous oxide, damage to cellular membranes and DNA, overproduction of lactate, overabundance of protein glycosylation storage products, overexpression of pathological enzyme isoforms, and leakage of cytochromes from organelles. Additionally, dysfunctional signal transduction pathways, especially in pathways involving phosphoinositide 3‑kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, RAS/Raf/ERK, and mammalian target of rapamycin (mTOR), have been implicated in malignant transformation and progression. Obesity and metabolic disorders, such as DM, may contribute to a dysfunctional immune system with a suppressed immune response by inducing a chronic inflammatory state, abnormal humoral and cellular mediated immunity, and lower counts and activity levels of natural killer (NK) cells and natural killer T cells (NKT cells). Recent advances in molecular biology will allow for better understanding of abnormal cellular pathways, as well as elucidating how metabolic disorders contribute to oncogenesis. Knowledge gained through these studies may lead to more efficacious oncologic therapies.

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