Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry (v.11, #4)
Omics technologies in diagnosis of lung adenocarcinoma by S. E. Novikova; L. K. Kurbatov; M. G. Zavialova; V. G. Zgoda; A. I. Archakov (309-340).
To date lung adenocarcinoma (LAC) is the most common type of lung cancer. Numerous studies on LAC biology resulted in identification of crucial mutations in oncogenes involved in activation of signaling pathways crucial for neoplastic transformation. Therapeutic approaches introduced in clinical practice significantly increase the survival rate of patients with LAC of different etiology. However, the main problem in the treatment of LAC consists in early diagnosis, taking into account both factors and mechanisms responsible in tumor initiation and progression. This problem may be solved by identification of a wide biomarker repertoire with high specificity and reliability of detection. In this context, proteins differentially expressed in normal and pathological conditions and suitable for detection in biological fluids appear to be the most promising biomarkers. The latter is especially important for minimally invasive diagnostic methods applicable at early stages of the disease. In this review we have analyzed literature data on studies aimed at search for LAC biomarkers by using a widerange of approaches and methods. The major attention has been paid to protein biomarkers as the most promising and convenient subjects of clinical diagnosis. The review also summarizes existing knowledge on posttranslational modifications, splice variants, isoforms, as well as model systems and transcriptome changes in LAC.
Keywords: lung adenocarcinoma; diagnosis; markers; proteins; proteomic methods; mass-spectrometry
Fibroblast growth factors and pancreas organogenesis by D. A. Gnatenko; E. P. Kopantsev; E. D. Sverdlov (341-348).
Fibroblast growth factors (FGFs) are growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we have summarized current information about the role of FGFs in pancreas organogenesis. The pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue and activation of various genes regulating particular stages thus determining specification of progenitor cells. Changes in the FGF/FGFR signaling pathway during this process result in incorrect activation of master genes, leading to different pathologies in pancreas development. Understanding the full picture about the role of FGFs in pancreas development will help better understanding of their role in other pathologies of the pancres, including carcinogenesis.
Keywords: growth factors; pancreas; master genes; organogenesis; pancreatic tumors
Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus by A. O. Shpakov (349-362).
Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (THs) are used to correct functions of the thyroid system. However, they are characterized by many side effects, including their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to impair insulin-producing function of the pancreas thus exacerbating diabetic pathology. In this context significant efforts have been made to develop TH analogues, selective for certain types of TH receptors that do not have these side effects. The peptide and lowmolecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, as well as metformin therapy and administration of antioxidants are effective for the treatment of thyroid pathology in patients with types 1 and 2 DM. In the review, the literature data and the results of own studies on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM have been summarized and analyzed.
Keywords: thyroid pathology; diabetes mellitus; thyroid hormones; low-molecular regulators; intranasally administered insulin; insulin resistance
Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson’s disease by E. V. Kryukova; I. V. Shelukhina; A. A. Kolacheva; A. Kh. Alieva; M. I. Shadrina; P. A. Slominsky; I. E. Kasheverov; Y. N. Utkin; M. V. Ugrumov; V. I. Tsetlin (363-370).
A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson’s disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative radioligand analysis of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, α-conotoxin MII, and α-bungarotoxin. These are selective ligands for different nAChR subtypes. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype. In the striatum epibatidine binding decreased by 66% and 70% at the presymptomatic and early symptomatic stages, respectively, while in SN epibatidine binding demonstrated a significant (160%) increase at the presymptomatic stage. The α-conotoxin MII binding to striatal dopaminergic axonal terminals at the presymptomatic stage decreased by 20% and at the symptomatic stage it demonstrated a further decrease. Striatal α-bungarotoxin binding increased at the presymptomatic stage and decreased at the early symptomatic stage. In SN, the level of α-bungarotoxin binding decreased at the presymptomatic stage and remained constant at the symptomatic stage. A significant decrease in the expression of Chrna4 and Chrna6 genes encoding α4 and α6 nAChR subunits was observed in SN at the early symptomatic stage, while a 13-fold increase in expression of the Chrna7 gene encoding the α7 nAChR subunit was detected at the presymptomatic stage. The data obtained on the altered mRNA levels or functional cholinergic receptors suggest possible involvement of nAChR in compensatory mechanisms at early PD stages.
Keywords: nicotinic acetylcholine receptors; dopaminergic neuron; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; striatum; substantia nigra