Infectious diseases and chronic inflammation are important risk factors for the development of malignant tumors in humans. One of the key infectious agents involved in human oncogenesis is the human papillomavirus (HPV). Non-muscle invasive bladder cancer is defined as a superficial neoplasia limited to the mucosa, aggravated by recurrence in 80 % of cases and progression in 30 % of cases. The development of this disease is associated with the influence of various carcinogenic agents, including HPV. Currently, a direct relationship has been revealed between the presence of viral DNA in the tumor tissue of the bladder and markers of proliferative activity, angiogenesis, and apoptosis factors. More and more researchers believe in the involvement of the virus in the development of recurrent forms of bladder cancer and the emergence of its invasive/poorly differentiated forms. Improving the diagnosis and postoperative monitoring of non-muscle invasive and muscle invasive bladder cancer is not possible without the improvement of minimally invasive molecular methods, which requires an understanding of the molecular mechanisms of HPV-associated carcinogenesis.Therefore, this review focuses on the analysis of the molecular mechanisms of HPV effect on progression of non-muscle invasive and muscle invasive bladder cancer. The features of miRNA expression in patients with papillomavirus infection of high oncogenic risk types and non-muscle invasive or muscle invasive bladder cancer are considered in detail. In particular, the role of miR-34а, -218, -20a, -424, -200a, -205-5p, -944, -100, -99a, -202, -30a, -145-5p, -195 and -199a-5 is described in the development and progression of bladder cancer. The mechanisms of disruption in the functioning of key cell signaling pathways during HPV integration in patients with bladder cancer, including changes in gene copy number and methylation level, are also considered.However, the number of HPV-positive tumor specimens that have been comprehensively analyzed using genome-wide studies in the literature remains small. Larger patient cohorts would be useful to further refine HPV-associated integration events and genomic changes, as well as to study clinical manifestations of the consequences of these alterations. Further research on the clinical implications of the observed genomic changes is needed to accurately stratify patients for targeted therapy, radiation and chemotherapy.
Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence. Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.
This article touches upon topical problems of modern medicine, representing the difficulty of timely diagnosis of oncological diseases of arduous localization and management of patients with malignant neoplasms. As an example, a clinical case of primary urethral melanoma is presented, illustrating a complex of aspects associated with the rarity of detecting malignant neoplasms of a given localization. The creation of standardized tactics for managing patients with rare malignant tumors and the correct interpretation of research results at the diagnostic stage, play an important role in improving the quality and life expectancy of patients. A step-by-step analysis of difficult situations will increase the alertness of doctors of all specialties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.