Various Stages Of Carcinogenesis Research Articles

Thiosulfinates: cytotoxic and antitumor activity

The pharmacological value of some natural compounds makes them attractive for use in oncology. Sulfur-containing thiosulfinates found in plants of the genus Allium have long been known as compounds with various therapeutic properties, including antitumor. In recent years, the effect of thiosulfinates on various stages of carcinogenesis has been actively studied. In vitro and in vivo studies have shown that thiosulfinates inhibit the proliferation of cancer cells, as well as induce apoptosis. The purpose of this review is to summarize current data on the use of natural and synthetic thiosulfinates in cancer therapy. Antitumor mechanisms and molecular targets of these promising compounds are discussed. A significant part of the review is devoted to the consideration of a new strategy for the treatment of oncological diseases - the use of the method of directed enzyme prodrug therapy with the possibility of obtaining antitumor thiosulfinates in situ.

MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.

In the past decade, significant advances in molecular research have provided a deeper understanding of the intricate regulatory mechanisms involved in carcinogenesis. MicroRNAs, short non-coding RNA sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. In the context of cancer, miRNA dysregulation is prevalent and closely associated with various stages of carcinogenesis, including initiation, progression, and metastasis. One crucial aspect of the cancer phenotype is the activity of histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting gene expression. Recent studies have revealed that miRNAs play a significant role in modulating these histone-modifying enzymes, leading to significant implications for genes related to proliferation, differentiation, and apoptosis in cancer cells. This article provides an overview of current research on the mechanisms by which miRNAs regulate the activity of histone-modifying enzymes in the context of cancer. Both direct and indirect mechanisms through which miRNAs influence enzyme expression are discussed. Additionally, potential therapeutic implications arising from miRNA manipulation to selectively impact histone-modifying enzyme activity are presented. The insights from this analysis hold significant therapeutic promise, suggesting the utility of miRNAs as tools for the precise regulation of chromatin-related processes and gene expression. A contemporary focus on molecular regulatory mechanisms opens therapeutic pathways that can effectively influence the control of tumor cell growth and dissemination.

Thiosulfinates: Cytotoxic and Antitumor Activity.

Pharmacological value of some natural compounds makes them attractive for use in oncology. The sulfur-containing thiosulfinates found in plants of the genus Allium have long been known as compounds with various therapeutic properties, including antitumor. Over the last few years, the effect of thiosulfinates on various stages of carcinogenesis has been actively investigated. In vitro and in vivo studies have shown that thiosulfinates inhibit proliferation of cancer cells, as well as they induce apoptosis. The purpose of this review is to summarize current data on the use of natural and synthetic thiosulfinates in cancer therapy. Antitumor mechanisms and molecular targets of these promising compounds are discussed. A significant part of the review is devoted to consideration of a new strategy for treatment of oncological diseases - use of the directed enzyme prodrug therapy approach aiming to obtain antitumor thiosulfinates in situ.

Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study

The regulation of apoptosis (the programmed cell death) is dependent on the crucial involvement of BCL2 and BAX. The Bax-248G>A and Bcl-2-938 C>A polymorphic variations in the promoter sequences of the Bax and Bcl-2 gene have been recently associated with low Bax expression, progression to advanced stages, treatment resistance, and shortened overall survival rate in some hematological malignancies, including chronic myeloid leukemia (CML) and other myeloproliferative neoplasms. Chronic inflammation has been linked to various stages of carcinogenesis wherein pro-inflammatory cytokines play diverse roles in influencing cancer microenvironment leading to cell invasion and cancer progression. Cytokines such as TNF-α and IL-8 have been implicated in cancer growth in both solid and hematological malignancies with studies showing their elevated levels in patients. Genomic approaches have in recent years provided significant knowledge with the regard to the association of certain SNPs (single nucleotide polymerphisms) either in a gene or its promoter that can influence its expression, with the risk and susceptibility to human diseases including cancer. This study has investigated the consequences of promoter SNPs in apoptosis genes Bax-248G>A (rs4645878)/Bcl-2-938C>A (rs2279115) and pro-inflammatory cytokines TNF-α rs1800629 G>A/IL-8 rs4073 T>A on the risk and susceptibility towards hematological cancers. The study design has 235 individuals both male and female enrolled as subjects that had 113 cases of MPDs (myeloproliferative disorders) and 122 healthy individuals as controls. The genotyping studies were conducted through ARMS PCR (amplification-refractory mutation system PCR). The Bcl-2-938 C>A polymorphism showed up in 22% of patients in the study, while it was observed in only 10% of normal controls. This difference in genotype and allele frequency between the two groups was significant (p = 0.025). Similarly, the Bax-248G>A polymorphism was detected in 6.48% of the patients and 4.54% of the normal controls, with a significant difference in genotype and allele frequency between the groups (p = 0.048). The results suggest that the Bcl-2-938 C>A variant is linked to an elevated risk of MPDs in the codominant, dominant, and recessive inheritance models. Moreover, the study indicated allele A as risk allele which can significantly increase the risk of MPDs unlike the C allele. In case of Bax gene covariants, these were associated with an increased risk of MPDs in the codominant inheritance model and dominant inheritance model. It was found that the allele A significantly enhanced the risk of MPDs unlike the G allele. The frequencies of IL-8 rs4073 T>A in patients was found to be TT (16.39%), AT (36.88%) and AA (46.72%), compared to controls who were more likely to have frequencies of TT (39.34%), AT (37.70%) and AA (22.95%) as such, respectively. There was a notable overrepresentation of the AA genotype and GG homozygotes among patients compared to controls in TNF-α polymorphic variants, with 6.55% of patients having the AA genotype and 84% of patients being GG homozygotes, compared to 1.63% and 69%, respectively in controls. The data from the current study provide partial but important evidence that polymorphisms in apoptotic genes Bcl-2-938C>A and Bax-248G>A and pro-inflammatory cytokines IL-8 rs4073 T>A and TNF-α G>A may help predict the clinical outcomes of patients and determine the significance of such polymorphic variations in the risk of myeloproliferative diseases and their role as prognostic markers in disease management using a case-control study approach.

Targeting Transcription Factors in Cancer: From "Undruggable" to "Druggable".

Deregulation of transcription factors is critical to hallmarks of cancer. Genetic mutations, gene fusions, amplifications or deletions, epigenetic alternations, and aberrant post-transcriptional modification of transcription factors are involved in the regulation of various stages of carcinogenesis, including cancer initiation, progression, and metastasis. Thus, targeting the dysfunctional transcription factors may lead to new cancer therapeutic strategies. However, transcription factors are conventionally considered as "undruggable." Here, we summarize the recent progresses in understanding the regulation of transcription factors in cancers and strategies to target transcription factors and co-factors for preclinical and clinical drug development, particularly focusing on c-Myc, YAP/TAZ, and β-catenin due to their significance and interplays in cancer.

Small Extracellular Vesicles: Functions and Potential Clinical Applications as Cancer Biomarkers.

Cancer, as the second leading cause of death worldwide, is a major public health concern that imposes a heavy social and economic burden. Effective approaches for either diagnosis or therapy of most cancers are still lacking. Dynamic monitoring and personalized therapy are the main directions for cancer research. Cancer-derived extracellular vesicles (EVs) are potential disease biomarkers. Cancer EVs, including small EVs (sEVs), contain unique biomolecules (protein, nucleic acid, and lipids) at various stages of carcinogenesis. In this review, we discuss the biogenesis of sEVs, and their functions in cancer, revealing the potential applications of sEVs as cancer biomarkers.

Role of Phytochemicals in Cancer Chemoprevention: Insights

Cancer is a condition where the body cells multiply in an uncontrollable manner. Chemoprevention of cancer is a broad term that describes the involvement of external agents to slow down or suppress cancer growth. Synthetic and natural compounds are found useful in cancer chemoprevention. The occurrence of global cancer type varies, depending on many factors such as environmental, lifestyle, genetic etc. Cancer is often preventable in developed countries with advanced treatment modalities, whereas it is a painful death sentence in developing and low-income countries due to the lack of modern therapies and awareness. One best practice to identify cancer control measures is to study the origin and risk factors associated with common types. Based on these factors and the health status of patients, stage, and severity of cancer, type of treatment is decided. Even though there are well-established therapies, cancer still stands as one of the major causes of death and a public health burden globally. Research shows that most cancers can be prevented, treated, or the incidence can be delayed. Phytochemicals from various medicinal plants were reported to reduce various risk factors associated with different types of cancer through their chemopreventive role. This review highlights the role of bioactive compounds or natural products from plants in the chemoprevention of cancer. There are many plant based dietary factors involved in the chemoprevention process. The review discusses the process of carcinogenesis and chemoprevention using plants and phytocompounds, with special reference to five major chemopreventive phytocompounds. The article also summarizes the important chemopreventive mechanisms and signaling molecules involved in the process. Since the role of antioxidants in chemoprevention is inevitable, an insight into plant-based antioxidant compounds that fight against this dreadful disease at various stages of carcinogenesis and disease progression is discussed. This will fill the research gap in search of chemopreventive natural compounds and encourage scientists in clinical trials of anticancer agents from plants.

ОЦЕНКА ВКЛАДА ОБЛУЧЕНИЯ В РАЗВИТИЕ МНОЖЕСТВЕННЫХ ОНКОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ В ОТДАЛЕННОМ ПЕРИОДЕ ОСТРОЙ ЛУЧЕВОЙ БОЛЕЗНИ

Purpose: On clinical examples to estimate a probable contribution of the postponed earlier external radiation of all body in the doses exceeding 1 Gy at development of multiple malignant neoplasms of different localization and a leukaemia.
 Material and methods: At 8 of 164 patients, it is long observed after the postponed acute radiation syndrome (ARS), multiple oncological diseases are revealed. Dynamics of consecutive forming of solid tumors at 2 patients and also malignant neoplasms and a myelodysplastic syndrome (MDS) with transformation in an acute leukamia at 1 patient is tracked. Observation duration – 31 years, 43 years and 32 years. 
 Results: Availability of medical care to the patients who transferred ARS and high quality of its rendering at all stages (out-patient, stationary) allowed to reveal malignant neoplasms at early stages of development and to achieve an absolute recovery. However eventually at these patients development and other oncological diseases was observed. The given clinical observations allow to assume that at presented cases radiation acted on various stages of carcinogenesis, and its contribution to development of different oncological diseases in all patients was not identical.
 Conclusion: The analysis of clinical observations allows to assume that radiation contribution to genesis of various oncological diseases at the persons which underwent radiation in the doses causing development of ARS is various. Now in our country there are no approaches to quantitative assessment of a contribution of radiation effects to development of malignant neoplasms in each case. The patients who underwent acute single exposition in doses over 1 Gy have to be considered as having predisposition to development of multiple tumors in the remote terms. In this regard they for life need medical follow up for the purpose of early diagnostics and adequate treatment of the developing malignant neoplasms.

HUMAN PAPILLOMAVIRUS INFECTION AND CERVICAL CANCER (OWERWIEW)

Viral infections are responsible for 15–20% of all human cancers. Infection with oncogenic viruses can contribute to various stages of carcinogenesis. Despite effective screening methods, cervical cancer continues to be a major public health problem. There are large differences in morbidity and mortality from cervical cancer by geographic region. The age-specific prevalence of HPV varies widely in different populations and has shown two peaks of HPV positiveness in young and older women. Around the world, there have been many studies on the epidemiology of HPV infection and oncogenic properties due to different HPV genotypes. However, there are still many countries where population prevalence has not yet been determined. Moreover, screening strategies for cervical cancer differ from country to country. Organized cervical screening programs are potentially more effectivethan opportunistic screening programs.Key words:Human papillomavirus, cervical cancer, screening, dysplasia

Anticancer potential of garlic and its bioactive constituents: A systematic and comprehensive review.

Vegetables of the Allium genus, such as garlic (Allium sativum L.), onions, shallots, leaks, and chives, have been used for many years for food consumption and for medicinal purposes. Historical medical texts have indicated the therapeutic applications of garlic as an antitumor, laxative, diuretic, antibacterial and antifungal agent. Specifically, garlic's antitumor abilities have been traced back 3500 years as a chemotherapeutic agent used in Egypt. Other beneficial effects of garlic consumption include lowering blood pressure, blood cholesterol, sugar and lipids. The processing and aging of garlic result in the production of non-toxic organosulfur by-products. These sulfur-containing compounds, such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, alliin, S-allylcysteine, and S-allylmercaptocysteine, impact various stages of carcinogenesis. The anticancer mechanisms of action of these garlic-derived phytochemicals include altering mitochondrial permeability, inhibiting angiogenesis, enhancing antioxidative and proapoptotic properties, and regulating cell proliferation. All these effects of garlic's sulfur-compounds have been demonstrated in various human cancers. The intent of this literature research is to explore the potential of garlic-derived products and bioactive organosulfur compounds as cancer chemopreventive and chemotherapeutic agents. This investigation employs criteria for systematic review and critically analyzes published in vitro, in vivo and clinical studies. Concerns and limitations that have arisen in past studies regarding standards of measurement, bioavailability, and method of delivery are addressed. Overall, it is hoped that through this systematic and comprehensive review, future researchers can be acquainted with the updated data assembled on anticancer properties of garlic and its phytoconstituents.

The Cervical Cancer (CC) Epidemiology and Human Papillomavirus (HPV) in the Middle East

Viral infections contribute 15–20 percent of all human cancers as a cause. Oncogenic virus infection may spur various stages of carcinogenesis. For several forms for HPV, about 15 associated with cancer. Following successful test techniques, cervical cancer remains a significant public health issue. Prevalence and mortality of per geographic area of cervical cancer were vastly different. The fourth most common cause of death from cancer among women is cervical cancer (CC). Human papillomavirus (HPV) infection in the cervix is the most significant risk factor for forming cervical cancer. Inflammation is a host-driven defensive technique that works rapidly to stimulate the innate immune response against pathogens such as viral infections. Inflammation is advantageous if it is brief and well-controlled; however, it can cause adverse effects if the inflammation is prolonged or is chronic in duration. HPV proteins are involved in the production of chronic inflammation, both directly and indirectly. Also, the age-specific prevalence of HPV differs significantly. Two peaks of HPV positive in younger and older people have seen in various populations. A variety of research has performed worldwide on the epidemiology of HPV infection and oncogenic properties due to specific HPV genotypes. Nevertheless, there are still several countries where population-dependent incidences have not yet identified. Additionally, the methods of screening for cervical cancer differ among countries.

<p>Circular RNA circTUBGCP3 Is Up-Regulated and Promotes Cell Proliferation, Migration and Survivability via Sponge mir-30b in Osteosarcoma</p>

PurposePrevailing evidences have demonstrated that circular RNAs (circRNAs) are closely associated with various stages of carcinogenesis. However, very few studies have delineated the specific mechanism of association between circRNAs and osteosarcoma (OS). It offers a novel insight that circRNAs can be explored as a potential therapeutic strategy for OS.Materials and MethodsIn this study, circTUBGCP3 was chosen from the existing reported circRNA microarray data obtained from OS cell lines and normal bone cells. Subsequently, qRT-PCR was performed to evaluate the expression level of circTUBGCP3 in OS samples and cell lines. Functional assays were conducted to estimate the impact of circTUBGCP3 on human OS cells proliferation, vitality, survivability, and migration. Western blot, luciferase reporter and in vivo tumorigenesis assays were performed to analyze the signaling pathways underlying the interaction of circTUBGCP3, miR-30b, and Vimentin.ResultsThe data indicate that circTUBGCP3 may act as a sponge of miR-30b that further alters the expression of Vimentin, and promotes the proliferation and metastatic properties of OS cells.ConclusioncircTUBGCP3 serves as a tumor promoter in tumorigenesis by increasing the possibilities of OS initiation and proliferation.

An in silico study on plant-derived inhibitors against a prognostic Biomarker, Jab1

Cancer kills millions of people worldwide every year. The main form of treatment at this point is chemotherapy, which comprises of systemic drug delivery so that they can kill the cancerous cells more effectively. But most of these drugs cause severe side effects in patients and, therefore there is a strong need to focus on identifying natural compounds as a potent phytoinhibitors using various in silico and in vitro approaches. Natural compounds pose low toxicity, hence render them to be an excellent alternative to the basis for the development of new anti-cancerous drugs. Our study considers an effective therapeutic target, Jab1 (c-Jun activation domain-binding protein-1) or a c-Jun coactivator, which has been implicated in multiple protein interactions that play a significant role in various stages of carcinogenesis. Hence we have performed screening of 1500 natural compounds having anticancerous activity by applying various in silico approaches including Lipinski rule of five, ADME, and various Molecular Docking tools. In this study, we have identified two potent phytoinhibitors against Jab1 which needs to be further validated through in vitro approaches.

Hypoxia-Inducible Factors and Cancer.

Hypoxia inducible factors (HIFs) mediate the transcription of hundreds of genes that allow cells to adapt to hypoxic environments. In this review, we summarize the current state of knowledge about mechanisms of HIF activation in cancer, as well as downstream cancer-promoting consequences such as altered substrate metabolism, angiogenesis, and cell differentiation. In addition, we examine the proposed relationship between respiratory-related hypoxia, HIFs, and cancer. HIFs are increased in many forms of cancer, and portend a poor prognosis and response to therapy. HIFs play a critical role in various stages of carcinogenesis. HIF and its transcription targets may be useful as biomarkers of disease and therapeutic targets for cancer.

The role and prognostic value of inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) in serous and mucinous epithelial ovarian tumours.

Understanding different mechanisms contributing to the aggressive behaviour of epithelial ovarian cancer (EOC) is a large challenge. Interaction between inflammation, immunity and carcinogenesis occurs in different cancers; however, the potential roles of different molecules involved in these processes in relation to ovarian carcinogenesis were not fully investigated. Inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) are implicated in carcinogenesis. iNOS is an NOS isoform that generates nitric oxide, which plays important roles in various stages of carcinogenesis. IL-33 is a cytokine implicated in modulation of anti-tumour immunity and tumour growth. This work aimed at studying the immunohistochemical expression of iNOS and IL-33 in serous and mucinous epithelial ovarian tumours to investigate their role and prognostic significance. Immunohistochemical expressions of iNOS and IL-33 were assessed in 90 patients with epithelial ovarian tumours (45 serous and 45 mucinous tumours, categorized as benign, borderline, and malignant tumours). iNOS and IL-33 showed significantly higher expressions in borderline and malignant serous and mucinous tumours compared to benign ones (p=0.0001). The differences between borderline and malignant tumours were statistically insignificant (p=0.2351&0.6321). iNOS showed significantly higher expression with increasing tumour grade in malignant mucinous tumours (p=0.0011). IL-33 showed significantly higher expression with increasing tumour grade in both malignant serous and mucinous tumours (p=0.0074 and 0.0007). Upregulation of iNOS and IL-33 expression in borderline and malignant epithelial ovarian tumours indicates their involvement in the development and progression of EOC, and their increased expression in less differentiated cancers suggests their association with poor prognosis in this category of tumours.

Extracellular Glycosaminoglycans in Management of Primary Hepatocellular Carcinoma Rather than Alpha Fetoprotein

Objectives: Extracellular matrix (ECM) is an essential player at various stages of carcinogenesis. Current study aims to evaluate diagnostic value of components of ECM, released to the serum, i.e. total glycosaminoglycans (TGAGs), total sialic acid (TSA) and free glucosamine (FGA) in primary HCC patients solely or confounded by other conditions (i.e. diabetes mellitus (DM), hepatitis C virus (HCV) or bilharziasis (B). Design and Methods: Our study was conducted upon 40 HCC patients: 32 (80%) males, 8 (20%) females, among these samples, patients with ascites, single/or multiple HCC lesions, as shown in demographic Table. Results: Liver and renal indices were significantly disturbed in HCC patients. Significant elevations of AFP, TGAGS and FGA, non-significant increases in TSA in HCC patients compared to normal control. These parameters except AFP showed significant persistent higher levels during cancer progression. AFP showed irrelevant changes to the stages of HCC lesion. HCC patients with HCV, DM or B showed significantly higher levels of AFP than with HCC solely. Both TGAGs and FGA showed the highest diagnostic accuracy over AFP, but TSA showed the lowest value. Conclusion: TGAGs and FGA may be regarded as cost-effective and more accurate diagnostic tools during primary HCC progression, whether solely, or commixed by other diseases.

In vitro and ex vivo vanadium antitumor activity in (TGF-β)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients

Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-β (TGF-β) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-β)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-β)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-β)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G0/G1 cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors.

Daily rhythm variations of the clock gene PER1 and cancer-related genes during various stages of carcinogenesis in a golden hamster model of buccal mucosa carcinoma.

BackgroundRecent studies have demonstrated that the clock gene PER1 regulates various tumor-related genes. Abnormal expressions and circadian rhythm alterations of PER1 are closely related to carcinogenesis. However, the dynamic circadian variations of PER1 and tumor-related genes at different stages of carcinogenesis remain unknown. This study was conducted to investigate the daily rhythm variation of PER1 and expression of tumor-related genes VEGF, KI67, C-MYC, and P53 in different stages of carcinogenesis.Materials and methodsDimethylbenzanthracene was used to establish a golden hamster model of buccal mucosa carcinogenesis. Hamsters with normal buccal mucosa, precancerous lesion, and cancerous lesion were sacrificed at six different time points during a 24-hour period of a day. Pathological examination was conducted using routine hematoxylin and eosin staining. PER1, VEGF, KI67, C-MYC, and P53 mRNAs were detected by real-time reverse transcriptase polymerase chain reaction, and a cosinor analysis was applied to analyze the daily rhythm.ResultsPER1, VEGF, C-MYC, and P53 mRNA exhibited daily rhythmic expression in three carcinogenesis stages, and KI67 mRNA exhibited daily rhythmic expression in the normal and precancerous stages. The daily rhythmic expression of KI67 was not observed in cancerous stages. The mesor and amplitude of PER1 and P53 mRNA expression decreased upon the development of cancer (P<0.05), whereas the mesor and amplitude of VEGF, KI67, and C-MYC mRNA increased upon the development of cancer (P<0.05). Compared with the normal tissues, the acrophases of PER1, VEGF, and C-MYC mRNA occurred earlier, whereas the acrophases of P53 and KI67 mRNA lagged remarkably in the precancerous lesions. In the cancer stage, the acrophases of VEGF and C-MYC mRNA occurred earlier and later, respectively, compared with the normal stage.ConclusionVariations in the daily rhythm characteristics of the clock gene PER1 and tumor-related genes VEGF, KI67, C-MYC, and P53 correlate with the development of cancer. Additional studies might provide new insights and methods to explore carcinogenic mechanisms and cancer treatment.

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.

The role of Helicobacter pylori in the process of 43 carcinogenesis by means of dysregulation of miRNA expression

Duodenal ulcer is associated with Helicobacter pylori almost in 90-100% of cases. Severe disease of the stomach - adenocarcinoma - is caused by infection with Helicobacter pylori in 70-90% of cases. Persons infected with this bacterium were proven statistically to be in group of the increased risk of the development of gastric cancer. Helicobacter pylori expresses a spectrum of virulence factors which cause dysregulation of intracellular signaling pathways in a host cell, that reduces the resistance to neoplastic transformation. In the review there are presented data about identified to the present time deregulated miRNAs associated with H.pylori diseases, including cancer of the stomach, and a few data on their biological significance. The growing number of studies confirming the involvement of miRNAs in various stages of carcinogenesis - from gastritis to the formation of metastases - demonstrates the importance of the new directions of the research.