N. A. Lisitsyn

Structure and function of enteric α-defensins in norm and pathology

The review summarizes the current data on the structure of enteric α-defensins, their functions in innate and adaptive immunity systems, and their role in intestinal illnesses.

A new immuno-PCR format for serological diagnosis of colon cancer

A new immuno-PCR format based on the detection of CDH17 membrane protein in serum exosomes is proposed. Using the technique described, it was possible to distinguish between serum specimens obtained from healthy donors and colon cancer patients. The results suggest that the new technique may enable the serological diagnosis of colon cancer in high-risk groups.

Role of exosomes and microvesicles in carcinogenesis

The review summarizes our current knowledge on the role of tumor-derived exosomes and microvesicles in the progression, metastasis, and angiogenesis of tumors, as well as in the suppression of adaptive and innate immunity.

A role of long noncoding RNAs in carcinogenesis

The review describes the changes observed in long noncoding RNA (lncRNA) content and function at various stages of carcinogenesis, as well as the prospects of lncRNA application in cancer prognosis.

Identification of proteins overexpressed in papillary thyroid tumors

A modified method of proteome comparative analysis based on preliminary removal of cell structural proteins by extraction using salt buffer and subsequent separation of extracts by two-dimensional gel electrophoresis was developed. Identification of differentially expressed proteins by mass spectrometry has revealed three proteins with noticeably increased level of synthesis in most samples of papillary thyroid tumors compared to normal tissues. An increase in ubiquitin content was found for the first time. Oncomarker search efficiencies by two-dimensional gel electrophoresis and bioinformatic search were compared.

Methods of searching for markers for serological serum diagnosis of tumors

This review describes the most popular methods of searching for serological markers of tumors that are used in a clinical setting, as well as a comparison of their efficiency.

Search for protein markers for serum diagnostics of tumors by analysis of microRNA expression profiles

New algorithm of bioinformatic search for potential serum tumor markers has been worked out, including: (1) identification of microRNAs with the level of synthesis most evidently and often decreasing in tumors; (2) search for target mRNAs regulated by microRNAs; (3) selection of targets encoding secretory proteins; (4) comparative analysis of transcription level of the targets in normal and tumor tissues. Practical use of the algorithm has allowed us to detect seven potential serum markers of colon tumors: ADAMTS14, ANGPT2, CCL7, DEFA5, MMP11, MMP14, and PLAU. It has been experimentally indicated that the level of synthesis of two of seven proteins (MMP14 and DEFA5) is significantly increased in colon tumors compared to normal tissue.

Estimation of the efficiency of 2D analysis and bioinformatics search in identification of protein markers for colon tumors

A modification of proteome differential analysis was developed; it comprises initial removal of the cell structural proteins by extraction with buffered saline and protein fractionation by gel filtration with subsequent separation by two-dimensional gel electrophoresis and identification by mass-spectrometry. This approach provided for detection of 12 proteins with significantly elevated expression levels in the majority of the analyzed malignant colorectal tumor specimens as compared with normal tissues. Increased contents of eight proteins were discovered for the first time. The efficiencies of the search for tumor markers by 2D analysis and serial analysis of gene expression (SAGE) were compared using the control panel of 19 potential colorectal tumor markers, identified earlier or independently found by other researchers. The 2D data for the control panel matched the earlier published data, whereas the search of SAGE database succeeded in detection only one-third of the markers.

Treatment with anti-cancer agents results in profound changes in lncRNA expression in colon cancer cells

Using real-time RT-PCR in combination with bioinformatics, we have shown for the first time that the treatment of HCT-116 and HT-29 colon cancer cells with two anti-cancer agents (doxycycline or 3,3′-diindolylmethane) results in profound changes in the intracellular content of several lncRNAs (by up to 100 times). Since many of these RNAs are secreted by tumors into the bloodstream, the obtained results provide a basis for developing more sensitive protocols for serological monitoring of tumor relapse and metastasis, as well as for search of new anti-cancer drugs.

Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.