Epithelial Origin Research Articles

Practical application of the CA-62 tumor marker in the initial diagnosis of oncological disease of epithelial origin: assistance to the doctor in interpreting the results

Aim. Demonstration the possibility of practical application of the highly sensitive tumor marker CA-62 in the initial diagnosis in asymptomatic patients with suspected cancer and/or the presence of pathological changes in instrumental studies, as well as describe the criteria for interpreting the results to help the doctor make a decision.
 Materials and methods. The article used the results and conclusions of blind clinical trials conducted to detect early stages of breast cancer (BC), prostate cancer (PC), colorectal cancer (CRC) and non-small cell lung cancer using the CA-62 tumor marker and other tumor markers. Statistical analysis was performed using the MedCalc program (MedCalc Software Ltd, Belgium). Diagnostic efficiency was assessed in terms of sensitivity, specificity, test accuracy, PPV and NPV, ROC analysis. The significance level was taken as p0.001.
 Results. The use of the standard cut-off value of 5000 U/ml of the CA-62 tumor marker makes it possible to achieve 97% sensitivity with 95% specificity in stage I BC. The combination of tumor markers CA-62 and CA 15-3 allows achieving 100% specificity in differentiation of BC and benign breast hyperplasia. The use of the CA-62 marker (6500 U/ml) in the gray zone of PSA 2.510 ng/ml improves the accuracy of detecting PC in biopsy from 35 to 93.1% with 90% sensitivity and 97% specificity. The use of a combination of tumor markers (CA-625000 U/ml, CYFRA 21-12.5 ng/ml and CEA5 ng/ml) will allow the doctor to improve the efficiency of differentiating lung cancer from chronic obstructive pulmonary disease. The combined use of markers (CEA3.5 ng/ml) and (CA-625000 U/ml) achieves 100% specificity with 97% sensitivity in detecting early stages of CRC.
 Conclusion. The article shows the possibilities of using the CA-62 marker, as well as new algorithms for the detection and differentiation of early stages of BC, PC, non-small cell lung cancer and CRC and benign neoplasms using the CA-62 marker in primary diagnosis. The use of the CA-62 tumor marker or its combination with other diagnostic methods can be a useful strategy for a comprehensive assessment of the risk of malignant neoplasms and increasing the diagnostic sensitivity of detecting early stages of cancer.

Multilineage circuits of regenerative cell states.

Regenerating the lungs' architecture after injury requires rebuilding its fibroelastic extracellular matrix scaffold. Konkimalla etal. establish that regenerative cell states (RCSs) of both epithelial and mesenchymal origin are functionally linked and indispensable for this process. Experimental ablation of RCSs causes organ degeneration, whereas their induction causes organ fibrosis.

MiRNA transcriptomics analysis shows miR-483-5p and miR-503-5p targeted miRNA in extracellular vesicles from severe acute pancreatitis-associated lung injury patients

AimThis study sought to identify potential biomarkers and miRNA-mRNA networks within extracellular vesicles (EVs) for detecting severe acute pancreatitis-associated lung injury (SAPALI). MethodsBlood-derived EVs were isolated, and their miRNA transcriptomic profiles were comprehensively analyzed using miRBase v.21 database along with miRDeep2 tool to predict novel miRNAs. DEGseq R package was deployed for the identification of differentially expressed miRNAs (DEMs). Protein-protein interaction (PPI) networks were assembled using STRING and Cytoscape. A lung injury model was established using Lipopolysaccharide (LPS)-induced BEAS-2B cells, chosen for their respiratory epithelial origin and pertinent association with lung injury. The expression levels of targeted miRNA and associated proteins, TLR4, NF-κB mRNA were quantified via RT-PCR and Western Blot. Levels of IL-6, IL-1β, TNF-α, and ROS were measured using designated kits. Dual-luciferase reporter assay was conducted to examine the interaction between miRNA and proteins. ResultsThe comparisons between the SAPALI and the control group revealed 10 DEM, including miR-503-5p and miR-483-5p. The cytoHubba plugin in Cytoscape identified three principal miRNA-mRNA interactions: miR-483-5p with PTK2 and HDAC2; miR-28-5p with MAPK1, TP53BP1, SEMA3A; and miR-503-5p with PPP1CB, SEMA6D, EPHB2, UNC5B. The SAPALI model exhibited elevated miR-503-5p, HDAC2 and inflammatory markers, with a decline UNC5B, miR-483-5p and miR-28-5p. Transfection with miR-503-5p and miR-483-5p inhibitors increased the levels of their supposed binding proteins but not miR-28-5p inhibitor. The Dual-luciferase reporter gene assay identified the interaction of miR-503-5p with UNC5B, and miR-483-5p with HDAC2, but not miR-28-5p with TP53BP1. ConclusionsOur study maps miRNA-mRNA interactions in SAPALI, identifying miR-503-5p and miR-483-5p as critical regulatory miRNAs.

Case Report: Adenoid cystic oral carcinoma of the buccal mucosa: a case report study

Adenoid cystic carcinoma is a rare tumor with epithelial cells origin in the jaw and face area. Here, we reported a case of this malignancy in the palate of a 43-years-old man. In this case report study, a 43-years-old man came to Shohada Qaen Hospital in January 2022 with a complaint of a sore in his mouth. An adenoid cystic based hypo-echo lesion was reported in the ultrasound. The pathological examination of the biopsy obtained by outpatient sampling method showed malignant neoplastic tissue with proliferation, hyperchromatic nucleus with false cyst appearance and cribriform glands, and the diagnosis of oral adenoid cystic carcinoma was confirmed. The patient was treated surgically. The prognosis of this tumor is different depend on the tissue of the mass, the clinical stage of the tumor, the site of involvement and the presence of vascular or perineural invasion.

High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer.

A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRASG12D . The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRASG12D detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma

BackgroundEpstein-Barr virus (EBV) is the first discovered human tumor virus that is associated with a variety of malignancies of both lymphoid and epithelial origin including nasopharyngeal carcinoma (NPC). The EBV-encoded latent membrane protein 1 (LMP1) has been well-defined as a potent oncogenic protein, which is intimately correlated with NPC pathogenesis. Anoikis is considered to be a physiological barrier to metastasis, and avoiding anoikis is a major hallmark of metastasis. However, the role of LMP1 in anoikis-resistance and metastasis of NPC has not been fully identified.MethodsTrypan blue staining, colony formation assay, flow cytometry, and TUNEL staining, as well as the detection of apoptosis and anoikis resistance‐related markers was applied to evaluate the anoikis-resistant capability of NPC cells cultured in ultra-low adhesion condition. Co-immunoprecipitation (Co-IP) experiment was performed to determine the interaction among LMP1, PRMT1 and PGC-1α. Ex vivo ubiquitination assay was used to detect the ubiquitination level of PGC-1α. Anoikis- resistant LMP1-positive NPC cell lines were established and applied for the xenograft and metastatic animal experiments.ResultsOur current findings reveal the role of LMP1-stabilized peroxisome proliferator activated receptor coactivator-1a (PGC-1α) in anoikis resistance and immune escape to support the invasion and metastasis of NPC. Mechanistically, LMP1 enhances PGC-1α protein stability by promoting the interaction between arginine methyltransferase 1 (PRMT1) and PGC-1α to elevate the methylation modification of PGC-1α, thus endowing NPC cells with anoikis-resistance. Meanwhile, PGC-1α mediates the immune escape induced by LMP1 by coactivating with STAT3 to transcriptionally up-regulate PD-L1 expression.ConclusionOur work provides insights into how virus-encoded proteins recruit and interact with host regulatory elements to facilitate the malignant progression of NPC. Therefore, targeting PGC-1α or PRMT1-PGC-1α interaction might be exploited for therapeutic gain for EBV-associated malignancies.

Regulation of Cell Adhesion and Migration via Microtubule Cytoskeleton Organization, Cell Polarity, and Phosphoinositide Signaling.

The capacity for cancer cells to metastasize to distant organs depends on their ability to execute the carefully choreographed processes of cell adhesion and migration. As most human cancers are of epithelial origin (carcinoma), the transcriptional downregulation of adherent/tight junction proteins (e.g., E-cadherin, Claudin and Occludin) with the concomitant gain of adhesive and migratory phenotypes has been extensively studied. Most research and reviews on cell adhesion and migration focus on the actin cytoskeleton and its reorganization. However, metastasizing cancer cells undergo the extensive reorganization of their cytoskeletal system, specifically in originating/nucleation sites of microtubules and their orientation (e.g., from non-centrosomal to centrosomal microtubule organizing centers). The precise mechanisms by which the spatial and temporal reorganization of microtubules are linked functionally with the acquisition of an adhesive and migratory phenotype as epithelial cells reversibly transition into mesenchymal cells during metastasis remains poorly understood. In this Special Issue of "Molecular Mechanisms Underlying Cell Adhesion and Migration", we highlight cell adhesion and migration from the perspectives of microtubule cytoskeletal reorganization, cell polarity and phosphoinositide signaling.

Next-Generation Modeling of Cancer Using Organoids.

In the last decade, organoid technology has become a cornerstone in cancer research. Organoids are long-term primary cell cultures, usually of epithelial origin, grown in a three-dimensional (3D) protein matrix and a fully defined medium. Organoids can be derived from many organs and cancer types and sites, encompassing both murine and human tissues. Importantly, they can be established from various stages during tumor evolution and recapitulate with high accuracy patient genomics and phenotypes in vitro, offering a platform for personalized medicine. Additionally, organoids are remarkably amendable for experimental manipulation. Taken together, these features make organoids a powerful tool with applications in basic cancer research and personalized medicine. Here, we will discuss the origins of organoid culture, applications in cancer research, and how cancer organoids can synergize with other models of cancer to drive basic discoveries as well as to translate these toward clinical solutions.

Clinical and Optical Coherence Tomography Correlation of Recurrence Patterns After Femtosecond Laser-Assisted Anterior Lamellar Keratoplasty in Reis-Bucklers Corneal Dystrophy.

The aim of this study was to report the clinical profile and patterns of recurrence after femtosecond laser-assisted anterior lamellar keratoplasty (FALK) in Reis-Bucklers corneal dystrophy. This is a case series of 5 eyes of 4 patients with Reis-Bucklers corneal dystrophy. Clinical images of recurrence were correlated with the high-resolution optical coherence tomography. Histopathologic examination of excised corneal samples was performed when possible. The median time to recurrence was 2 (1-5) years after FALK. Of the 5 eyes, 1 eye had primary FALK, whereas 4 eyes had secondary interventions, which included previous phototherapeutic keratectomy (once in 1 eye and twice in 2 eyes), and previous penetrating keratoplasty, followed by phototherapeutic keratectomy (1 eye). Recurrence was noted at the level of the subepithelium. In addition, 1 eye showed interface deposits along with epithelial downgrowth at the graft-host bed. The 2 distinct patterns of recurrence noted were at the subepithelial region and the interface. The clinical patterns of recurrence favor an epithelial origin of recurrent deposits.

Patho-morphological and Immunohistochemical Studies on Bovine Horn Core Carcinoma

Background: An investigation was carried out on twelve clinical cases of neoplasm of horn in Durg, Dhamtari and Rajnandgaon districts of Chhattisgarh, suspected of bovine horn core carcinoma (squamous cell carcinoma) revealed the cytology, pathomorphology and immunohistochemical (IHC) expression of Pan-cytokeratin (Pan- CK), p53 gene, epidermal growth factor receptor (EGFR) and p16 gene in tumourous growth at horn in bovines. Methods: In this field-laboratory investigation conducted during January to June 2022, we explicate the cytological, pathological and immunohistochemical alterations in bovine horn core carcinoma from 12 tissue samples. Cytological studies includes special papaniculaou staining and immunohistochemistry was performed through Benchmark automated staining system. Result: Eight out of 12 cases (66.66%) were confirmed as SCC of horn on the basis of histopathological and immunohistochemical analysis. Papanicolaou staining revealed variation in shape and size of cells and altered nuclear details. Grossly unilateral large cauliflower like neoplastic growth at the base of the horn was observed. Differentiation of tumours were based on histopathology and Immunohistochemistry. Well differentiated SCCs (n=4; 50%) were characterized by severe keratinization of horn epithelium with concentric arrangement forming keratin pearls also called as “cell nests”. Moderately differentiated SCCs (n=2; 25%) characterized by small keratin pearl formations and mitotic figures. Poorly differentiated SCCs of horn (n=2; 25%) revealed absence of distinctive keratin pearls although deep invasion from primary site was observed. Tissue samples revealed strong immunohistochemical staining of Pan-CK, p53 and EGFR and negative to p16. Highest immunohistochemical expression was observed in Pan-CK which confirmed the tumours were of epithelial origin and EGFR immunoexpression was confirmatory for malignancy and degree of metastasis.

Synthetic circuits based on split Cas9 to detect cellular events

Synthetic biology involves the engineering of logic circuit gates that process different inputs to produce specific outputs, enabling the creation or control of biological functions. While CRISPR has become the tool of choice in molecular biology due to its RNA-guided targetability to other nucleic acids, it has not been frequently applied to logic gates beyond those controlling the guide RNA (gRNA). In this study, we present an adaptation of split Cas9 to generate logic gates capable of sensing biological events, leveraging a Cas9 reporter (EGxxFP) to detect occurrences such as cancer cell origin, epithelial to mesenchymal transition (EMT), and cell–cell fusion. First, we positioned the complementing halves of split Cas9 under different promoters—one specific to cancer cells of epithelial origin (phCEA) and the other a universal promoter. The use of self-assembling inteins facilitated the reconstitution of the Cas9 halves. Consequently, only cancer cells with an epithelial origin activated the reporter, exhibiting green fluorescence. Subsequently, we explored whether this system could detect biological processes such as epithelial to mesenchymal transition (EMT). To achieve this, we designed a logic gate where one half of Cas9 is expressed under the phCEA, while the other is activated by TWIST1. The results showed that cells undergoing EMT effectively activated the reporter. Next, we combined the two inputs (epithelial origin and EMT) to create a new logic gate, where only cancer epithelial cells undergoing EMT activated the reporter. Lastly, we applied the split-Cas9 logic gate as a sensor of cell–cell fusion, both in induced and naturally occurring scenarios. Each cell type expressed one half of split Cas9, and the induction of fusion resulted in the appearance of multinucleated syncytia and the fluorescent reporter. The simplicity of the split Cas9 system presented here allows for its integration into various cellular processes, not only as a sensor but also as an actuator.

Organoids and metastatic orthotopic mouse model for mismatch repair-deficient colorectal cancer.

Genome integrity is essential for the survival of an organism. DNA mismatch repair (MMR) genes (e.g., MLH1, MSH2, MSH6, and PMS2) play a critical role in the DNA damage response pathway for genome integrity maintenance. Germline mutations of MMR genes can lead to Lynch syndrome or constitutional mismatch repair deficiency syndrome, resulting in an increased lifetime risk of developing cancer characterized by high microsatellite instability (MSI-H) and high mutation burden. Although immunotherapy has been approved for MMR-deficient (MMRd) cancer patients, the overall response rate needs to be improved and other management options are needed. To better understand the biology of MMRd cancers, elucidate the resistance mechanisms to immune modulation, and develop vaccines and therapeutic testing platforms for this high-risk population, we generated organoids and an orthotopic mouse model from intestine tumors developed in a Msh2-deficient mouse model, and followed with a detailed characterization. The organoids were shown to be of epithelial origin with stem cell features, to have a high frameshift mutation frequency with MSI-H and chromosome instability, and intra- and inter-tumor heterogeneity. An orthotopic model using intra-cecal implantation of tumor fragments derived from organoids showed progressive tumor growth, resulting in the development of adenocarcinomas mixed with mucinous features and distant metastasis in liver and lymph node. The established organoids with characteristics of MSI-H cancers can be used to study MMRd cancer biology. The orthotopic model, with its distant metastasis and expressing frameshift peptides, is suitable for evaluating the efficacy of neoantigen-based vaccines or anticancer drugs in combination with other therapies.

Pancreatic duct organoid swelling is chloride-dependent

Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO3 levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.

Maligne Neoplasien der Orbita

Malignant masses of the orbit include a large variety of neoplasms of epithelial or mesenchymal origin. The treatment of orbital malignancies is an essential interdisciplinary field of medicine that integrates ENT medicine, facial surgery, plastic surgery, neurosurgery, oncology and radiology.The main symptom of malignant orbital masses is the exophthalmos. A symptom that can help to differentiate a benign from a malignant orbital mass can be the pain. The main diagnostic tool is the MRI including new sequences like DWI and DCE.After presenting symptoms and diagnostic strategies of malignant orbital masses, this article starts with the description of malignant epithelial neoplasms of the lacrimal gland. Furthermore, it describes new insights in orbital lymphomas, followed by the discussion of semimalignant orbital masses. Last but not least the text deals with malignant neoplasms of the skin that can grow secondarily in the orbit. Finally, the manuscript discusses orbital metastases.

Expression of stem cell markers SALL4, LIN28A, and KLF4 in ameloblastoma

BackgroundAmeloblastoma (AME) is a benign odontogenic tumour of epithelial origin characterised by slow but aggressive growth, infiltration, and recurrence; it is capable of reaching large dimensions and invading adjacent structures. Stem cell research has proven to be significant in the sphere of tumour biology through these cells’ possible involvement in the aetiopathogenesis of this tumour.MethodsImmunohistochemistry was performed on AME, dentigerous cyst (DC), and dental follicle (DF) samples, and indirect immunofluorescence was performed on the AME-hTERT cell line to determine the expression of SALL4, LIN28A, and KLF4.ResultsExpression of proteins related to cellular pluripotency was higher in AME cells than in DC and DF cells. The analysis revealed that the proteins in question were mainly expressed in the parenchyma of AME tissue samples and were detected in the nuclei of AME-hTERT cells.ConclusionsStem cells may be related to the origin and progression of AME.

Regulatory roles of Osteopontin in lung epithelial inflammation and epithelial-telocyte interaction.

Lung epithelial cells play important roles in lung inflammation and injury, although mechanisms remain unclear. Osteopontin (OPN) has essential roles in epithelial damage and repair and in lung cancer biological behaviours. Telocyte (TC) is a type of interstitial cell that interacts with epithelial cells to alleviate acute inflammation and lung injury. The present studies aim at exploring potential mechanisms by which OPN regulates the epithelial origin lung inflammation and the interaction of epithelial cells with TCs in acute and chronic lung injury. The lung disease specificity of OPN and epithelial inflammation were defined by bioinformatics. We evaluated the regulatory roles of OPN in OPN-knockdown or over-expressed bronchial epithelia (HBEs) challenged with cigarette smoke extracts (CSE) or in animals with genome OPN knockout (gKO) or lung conditional OPN knockout (cKO). Acute lung injury and chronic obstructive pulmonary disease (COPD) were induced by smoking or lipopolysaccharide (LPS). Effects of OPN on PI3K subunits and ERK were assessed using the inhibitors. Spatialization and distribution of OPN, OPN-positive epithelial subtypes, and TCs were defined by spatial transcriptomics. The interaction between HBEs and TCs was assayed by the co-culture system. Levels of OPN expression increased in smokers, smokers with COPD, and smokers with COPD and lung cancer, as compared with healthy nonsmokers. LPS and/or CSE induced over-production of cytokines from HBEs, dependent upon the dysfunction of OPN. The severity of lung inflammation and injury was significantly lower in OPN-gKO or OPN-cKO mice. HBEs transferred with OPN enhanced the expression of phosphoinositide 3-kinase (PI3K)CA/p110α, PIK3CB/p110β, PIK3CD/p110δ, PIK3CG/p110γ, PIK3R1, PIK3R2 or PIK3R3. Spatial locations of OPN and OPN-positive epithelial subtypes showed the tight contact of airway epithelia and TCs. Epithelial OPN regulated the epithelial communication with TCs, and the down-regulation of OPN induced more alterations in transcriptomic profiles than the up-regulation. Our data evidenced that OPN regulated lung epithelial inflammation, injury, and cell communication between epithelium and TCs in acute and chronic lung injury. The conditional control of lung epithelial OPN may be an alternative for preventing and treating epithelial-origin lung inflammation and injury.

Drosophila as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins.

Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by the induction of cellular senescence, and additional mutations are required to induce tumor progression. Therefore, identifying cooperating cancer genes is of paramount importance. Recently, the tensin family of focal adhesion proteins, TNS1-4, have emerged as regulators of carcinogenesis, yet their role in cancer appears somewhat controversial. Around 90% of human cancers are of epithelial origin. We have used the Drosophila wing imaginal disc epithelium as a model system to gain insight into the roles of two orthologs of human TNS2 and 4, blistery (by) and PVRAP, in epithelial cancer progression. We have generated null mutations in PVRAP and found that, as is the case for by and mammalian tensins, PVRAP mutants are viable. We have also found that elimination of either PVRAP or by potentiates RasV12-mediated wing disc hyperplasia. Furthermore, our results have unraveled a mechanism by which tensins may limit Ras oncogenic capacity, the regulation of cell shape and growth. These results demonstrate that Drosophila tensins behave as suppressors of Ras-driven tissue hyperplasia, suggesting that the roles of tensins as modulators of cancer progression might be evolutionarily conserved.

Modelling Cell Orientation Under Stretch: The Effect of Substrate Elasticity

When cells are seeded on a cyclically deformed substrate like silicon, they tend to reorient their major axis in two ways: either perpendicular to the main stretching direction, or forming an oblique angle with it. However, when the substrate is very soft such as a collagen gel, the oblique orientation is no longer observed, and the cells align either along the stretching direction, or perpendicularly to it. To explain this switch, we propose a simplified model of the cell, consisting of two elastic elements representing the stress fiber/focal adhesion complexes in the main and transverse directions. These elements are connected by a torsional spring that mimics the effect of crosslinking molecules among the stress fibers, which resist shear forces. Our model, consistent with experimental observations, predicts that there is a switch in the asymptotic behaviour of the orientation of the cell determined by the stiffness of the substratum, related to a change from a supercritical bifurcation scenario, whereby the oblique configuration is stable for a sufficiently large stiffness, to a subcritical bifurcation scenario at a lower stiffness. Furthermore, we investigate the effect of cell elongation and find that the region of the parameter space leading to an oblique orientation decreases as the cell becomes more elongated. This implies that elongated cells, such as fibroblasts and smooth muscle cells, are more likely to maintain an oblique orientation with respect to the main stretching direction. Conversely, rounder cells, such as those of epithelial or endothelial origin, are more likely to switch to a perpendicular or parallel orientation on soft substrates.

Clinical significance of detection of micrometastases in lymph nodes in ovarian cancer

Ovarian cancer of epithelial origin is the most common type of oncological process in this organ and is characterized by a high probability of fatal outcome. It is believed that this is due to insufficiently effective diagnosis of the prevalence and severity of this disease. This review presents data on the development of disease recurrence in a significant number of patients after cytoreductive surgery. According to some authors, the reason for the high risk of recurrence is the insufficient information content of the method of studying histological preparations of regional lymph nodes after staining with hematoxylin and eosin to detect small-sized metastases, including isolated tumor cells and micrometastases. To improve the accuracy of such diagnostics, it is recommended to supplement the study of multilevel sections of lymph nodes using routine staining with the use of immunohistochemistry and other methods using various antibodies to cytokeratins, along with other epithelial markers. The review provides an analysis of the opinions of various researchers on the prognostic significance of the detection of micrometastases in the lymph nodes, which can increase the effectiveness of therapy due to a more accurate assessment of the prevalence of the disease and correction of the tactics of treating patients with various oncological diseases.

Relationship between cluster miR-143/145 micro-RNAs with oncogenesis: tissue and cellular context

The purpose of the study was to present up-to-date data on the regulation of expression, function in normal tissues and multidirectional activity in the oncogenesis of miR-143/145 microRNAs cluster, as well as to evaluate the possibilities and limitations of the therapeutic use of microRNAs of this cluster in malignant neoplasms. Material and methods. The search for available domestic and foreign literary sources published in PubMed and RSCI databases over the past 10 years has been carried out. 427 articles were found, of which 41 were included in this review. Results. The conservative cluster miR-143/145 is one of the most intensively studied in tumors. Based on the results of the analysis of differential miRNA expression, in vitro experiments in cancer cell lines and in vivo in mouse tumor models, a decrease in miR-143 and miR-145 levels was shown in malignant neoplasms of epithelial origin. Until recently, these miRNAs were considered classical oncosuppressors. The data presented in the review demonstrate that the results of a number of studies taking into account the cellular aspects of microRNA expression contradict this concept. miR-143 microRNA, for example, is known to participate in the metabolic restructuring of the tumor and the activation of neoangiogenesis. It has been shown that the oncosuppressive or pro-oncogenic activity of miR-143 and miR-145 depend on the tissue and cellular context and can be explained by the presence of several regulated targets that have opposite effects on oncogenesis. Taken together, the data obtained suggest the need to exercise caution when choosing the microRNAs of the described cluster for exogenous therapeutic delivery. Conclusion. Further detailed decoding of the mechanisms of miR-143 and miR-145 functioning in various types of tissues and cells, as well as identification of new MRNA targets are necessary for a better understanding of the involvement of these molecules in oncogenesis.