This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in the human body. The features of the biochemical processes occurring in breast cancer are described, ranging from nonspecific, at first glance, and strictly biochemical to hormone-induced reactions, genetic and epigenetic regulation, which allows for a broader and deeper understanding of the principles of oncogenesis, as well as maintaining the viability of cancer cells in the mammary gland. Specific pathways of the activation of oxidative stress have been studied as a response to the overproduction of stress hormones and estrogens, and specific ways to reduce its negative impact have been described. The diversity of participants that trigger redox reactions from different sides is considered more fully: glycolytic activity in breast cancer, and the nature of consumption of amino acids and metals. The role of metals in oxidative stress is discussed in detail. They can act as both co-factors and direct participants in oxidative stress, since they are either a trigger mechanism for lipid peroxidation or capable of activating signaling pathways that affect tumorigenesis. Special attention has been paid to the genetic and epigenetic regulation of breast tumors. A complex cascade of mechanisms of epigenetic regulation is explained, which made it possible to reconsider the existing opinion about the triggers and pathways for launching the oncological process, the survival of cancer cells and their ability to localize.
1 April 2020 in Journal of Oral Biology and Craniofacial Research
The aim of the work is to study the metabolic characteristics of saliva in lung cancer for use in early diagnosis and determining the prognosis of the disease. The patient group included 425 lung cancer patients, 168 patients with non-cancerous lung diseases, and 550 healthy volunteers. Saliva samples were collected from all participants in the experiment before treatment and 34 biochemical saliva parameters were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 (StatSoft) program and R package (version 3.2.3). To construct the classifier, the Random Forest method was used; the classification quality was assessed using the cross-validation method. Prognostic factors were analyzed by multivariate analysis using Cox’s proportional hazard model in a backward step-wise fashion to adjust for potential confounding factors. A complex of metabolic changes occurring in saliva in lung cancer is described. Seven biochemical parameters were identified (catalase, triene conjugates, Schiff bases, pH, sialic acids, alkaline phosphatase, chlorides), which were used to construct the classifier. The sensitivity and specificity of the method were 69.5% and 87.5%, which is practically not inferior to the diagnostic characteristics of markers routinely used in the diagnosis of lung cancer. Significant independent factors in the poor prognosis of lung cancer are imidazole compounds (ICs) above 0.478 mmol/L and salivary lactate dehydrogenase activity below 545 U/L. Saliva has been shown to have great potential for the development of diagnostic and prognostic tests for lung cancer.
This review analyzed 21 scientific papers on the determination of amino acids in various types of cancer in saliva. Most of the studies are on oral cancer (8/21), breast cancer (4/21), gastric cancer (3/21), lung cancer (2/21), glioblastoma (2/21) and one study on colorectal, pancreatic, thyroid and liver cancer. The amino acids alanine, valine, phenylalanine, leucine and isoleucine play a leading role in the diagnosis of cancer via the saliva. In an independent version, amino acids are rarely used; the authors combine either amino acids with each other or with other metabolites, which makes it possible to obtain high values of sensitivity and specificity. Nevertheless, a logical and complete substantiation of the changes in saliva occurring in cancer, including changes in salivary amino acid levels, has not yet been formed, which makes it important to continue research in this direction.