Epigenetic disorders such as point mutations in cellular tumor suppressor genes, DNA methylation and post-translational modifications are needed to transformation of normal cells into cancer cells. ...These events result in alterations in critical pathways responsible for maintaining the normal cellular homeostasis, triggering to an inflammatory response which can lead the development of cancer. The inflammatory response is a universal defense mechanism activated in response to an injury tissue, of any nature, that involves both innate and adaptive immune responses, through the collective action of a variety of soluble mediators. Many inflammatory signaling pathways are activated in several types of cancer, linking chronic inflammation to tumorigenesis process. Thus, Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, growth, invasion, and metastasis, affecting also the immune surveillance. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. A range of inflammation mediators, including cytokines, chemokines, free radicals, prostaglandins, growth and transcription factors, microRNAs, and enzymes as, cyclooxygenase and matrix metalloproteinase, collectively acts to create a favorable microenvironment for the development of tumors. In this review are presented the main mediators of the inflammatory response and discussed the likely mechanisms through which, they interact with each other to create a condition favorable to development of cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Inflammation is a defense strategy against invading agents and harmful molecules that is activated immediately following a stimulus, and involves the release of cytokines and chemokines, which ...activate the innate immune response. These mediators act together to increase blood flow and vascular permeability, facilitating recruitment of effector cells to the site of injury. Following resolution of the injury and removal of the stimulus, inflammation is disabled, but if the stimulus persists, inflammation becomes chronic and is strongly associated with cancer. This is likely to be due to the fact that the inflammation leads to a wound that does not heal, requiring a constant renewal of cells, which increases the risk of neoplastic transformation. Debris from phagocytosis, including the reactive species of oxygen and nitrogen that cause damage to DNA already damaged by the leukotrienes and prostaglandins, has an impact on inflammation and various carcinogenic routes. There is an association between chronic inflammation, persistent infection and cancer, where oncogenic action is mediated by autocrine and paracrine signals, causing changes in somatic cells under the influence of the microbial genome or of epigenetic factors. Among the infectious agents associated with cancer, certain genotypes of human papillomavirus (HPV) stand out. HPV is responsible for virtually all cases of cervical cancer and a lower proportion of cancers of the vagina, vulva, anus, penis and a number of extragenital cancers. In the present review, recent advances in the mechanisms involved in the inflammatory response are presented with their participation in the process of carcinogenesis, emphasizing the role of chronic inflammation in the development of HPV-induced cervical cancer.
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Biology and pathogenesis of human osteosarcoma de Azevedo, Judson Welber Veríssimo; de Medeiros Fernandes, Thales Allyrio Araújo; Fernandes, Jr, José Veríssimo ...
Oncology letters,
02/2020, Volume:
19, Issue:
2
Journal Article
Open access
Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the ...tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines.
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Macrophage migration inhibitory factor (MIF) emerged in recent years as an important inflammation mediator, playing a prominent role in the pathogenesis of various types of malignant neoplasm. MIF is ...a glycoprotein that presents a wide spectrum of biological activities and exerts a complex interaction with various cellular signaling pathways, causing imbalance of homeostasis. Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors. The production of MIF is triggered through an autocrine signal emitted by tumor cells, and stimulates the production of cytokines, chemokines, and growth as well as angiogenic factors that lead to growth of the tumor, increasing its aggressiveness and metastatic potential. MIF is produced by virtually all types of human body cells, in response to stress caused by different factors, leading to pathological conditions such as chronic inflammation and immunomodulation with suppression of immune surveillance and of immune response against tumors, angiogenesis, and carcinogenesis. In this review, we present recent advances on the biological activity of MIF, the signaling pathways with which it is involved and their role in tumorigenesis.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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The Role of Extracellular Traps in HIV Infection da Silva, Natanias Macson; Leite, Nicolas Patrícius de Medeiros; Carvalho, Amanda Estevam ...
AIDS research and human retroviruses,
05/2024, Volume:
40, Issue:
5
Journal Article
Peer reviewed
Human immunodeficiency virus (HIV) infection is still an important public health problem, which justifies the research of new therapies to combat it. Recent studies show that Extracellular Traps ...(ETs) are cellular mechanisms useful in the capture and destruction of some viruses, such as the HIV. Here, we show that neutrophils from peripheral blood, genital tissues, and placenta are activated when exposed to human immunodeficiency virus type 1 (HIV-1) and release Neutrophil Extracellular Traps (NETs). The NETs can capture, neutralize, and inactivate the virus and, also, protect other target cells from HIV infection, as long as the DNA and other constituents of the NETs remain intact. Further, the review indicates that the immunoprotective role of NETs in the context of HIV-1 infection is a promising finding for the development of new antiviral therapies. It is necessary, however, the development of studies that evaluate the tissue injury that NETs can cause and the biological relationships with other cells to improve them as therapeutic targets.
Th17 response in patients with cervical cancer Alves, Jayra Juliana Paiva; De Medeiros Fernandes, Thales Allyrio Araújo; De Araújo, Josélio Maria Galvão ...
Oncology letters,
11/2018, Volume:
16, Issue:
5
Journal Article
Open access
Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and ...progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.
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The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. ...Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic β-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic β-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.
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Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children, young adults, and the elderly. It is an aggressive cancer with a poor prognosis, exhibiting low survival rates ...even with standard treatment. Recently, circular RNA molecules capable of influencing gene expression through various functions, with their main role being acting as microRNA sponges and reducing their intracellular expression, have been identified. Recent studies have linked circular RNAs to osteosarcoma development and progression. Therefore, the present study aimed to investigate the alteration in circular RNA expression during osteosarcoma development and progression.
An integrative literature review was conducted from September 10th to November 12th, 2021, using the following databases: PubMed/MEDLINE, SCOPUS, Web of Science, OVID, and EMBASE. 129 full articles were included in the review. The obtained data were organized using a standardized data collection instrument, which included the following information: altered expression profile of circular RNAs, associated cancer hallmarks, clinical-pathological relationships of circular RNAs, and perspectives on the studied circular RNAs.
A total of 94 distinct circular RNAs were identified, predominantly showing an increased expression pattern. Approximately 91% of the studies that aimed to identify the mechanisms of action of circular RNAs highlighted the function of circular RNAs as microRNA sponges. The most associated cancer hallmarks with the identified circular RNAs were proliferative signaling induction, invasion and metastasis, and resistance to cell death. The altered expression of these circular RNAs generally correlated with a worse prognosis for patients, as evidenced by clinical features such as shorter survival, advanced Enneking and/or TNM stage, higher incidence of metastasis, larger tumor size, and increased chemoresistance.
These findings indicate the significance of circular RNA molecules in osteosarcoma carcinogenesis, suggesting their potential as new prognostic and/or diagnostic biomarkers, as well as alternative therapeutic targets in the fight against osteosarcoma.
Objetivo Describir las tasas de mortalidad por cancer de cuello uterino y sus tendencias, asi como analizar las correlaciones espaciales de este tipo de cancer en Natal-RN, Brasil, entre 2000 y 2012. ...Materiales y Metodos Para el analisis estadistico se utilizaron el modelo de regresion lineal simple, la estimacion empirica de Bayes y el indice Moran Global. Resultados La tasa de mortalidad por cancer de cuello uterino en Natal, estandarizado por rango de edad, fue 5.5 por cada 100 000 mujeres. Todas las series historicas para los coeficientes estudiados se clasificaron como estables. El indice Moran Global obtenido fue 0.048, con un valor p de 0.300 para la correlacion de prueba espacial entre vecindarios. El ingreso familiar promedio por vecindario no mostro correlacion significativa con las tasas de mortalidad por cancer de cuello uterino. Conclusion En este estudio se observo una tendencia temporal de estabilizacion e independencia espacial de la tasa de mortalidad por cancer cervical en mujeres de Natal, asi como la ausencia de correlacion entre estas tasas y el ingreso familiar promedio de las mujeres participantes, distribuidas por vecindarios de la ciudad. En vista de esto, se sugiere que se adopten cambios en las politicas publicas dirigidas a la prevencion de la enfermedad que apunten a medidas que puedan tener un impacto positivo en el programa de monitoreo, mejorando la cobertura de la prueba de Papanicolaou, asi como de las campanas de vacunacion contra el VPH, con el objetivo de revertir esta tendencia y lograr una reduccion en las tasas de mortalidad de la enfermedad. Palabras Clave: Neoplasias del cuello uterino; mortalidad; analisis espaciotemporal (fuente: DeCS, BIREME). Objective To describe cervical cancer mortality rates and their corresponding trends, and to analyze the spatial correlations of this type of cancer in Natal-RN, Brazil, between 2000 and 2012. Materials and Methods The simple linear regression model, the empirical Bayes method and the Global Moran's index were used for the statistical analysis. Results The mortality coefficient of cervical cancer in Natal, standardized by age range, was 5.5 per 100 000 women. All historical series for the coefficients studied were classified as stable. The Global Moran's index obtained was 0.048, with a p-value for the spatial test correlation between neighborhoods of 0.300. The average family income by neighborhood showed no significant correlation to cervical cancer mortality rates. Conclusion This study found a temporal stabilization and spatial independence trend of cervical cancer mortality rates in women from Natal, as well as the absence of correlation between these rates and the average family income of the of the participating women distributed by neighborhoods. In view of this, changes in the public policies should be made aimed at preventing the disease; adopting these measures could positively impact the screening program, improving the coverage of Pap smears and immunization campaigns against HPV, in order to reverse this trend and achieve a reduction of mortality rates. Key Words: Uterine cervical neoplasm; mortality; spatiotemporal analysis (source: MeSH, NLM).
Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced ...cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.
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