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Information × Registration Number 0226U001788, (0125U000655) , R & D reports Title Development of technology for identification of stress-induced factors of initiation of bone tissue metastatic lesion. popup.stage_title Ідентифікація стрес-індукованих молекулярно-біологічних маркерів, залучених у процеси ремоделювання кісткової тканини, in silico та in vitro. Head Chekhun Vasyl F., д.мед.н. Registration Date 30-01-2026 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine popup.description1 To identify molecular and biological markers of early diagnosis, as key drivers of the initiation of osteoblastic and osteoclastic processes, under the conditions of metastatic and traumatic damage and regeneration of bone tissue against the background of changes in the landscape of acute and chronic stress factors. popup.description2 Based on a bioinformatic analysis using the Gene Expression Omnibus database, a gene expression pattern associated with the response to endogenous factors of chronic stress and the development of castration-resistant prostate cancer was identified. Functional analysis performed using the online tool ShinyGO 0.8 made it possible to establish that the protein products of the identified genes are involved in the regulation of ferroptosis, insulin resistance, cellular metabolism, as well as cytokine signaling, in particular IL-2, IL-4, and TGF-β signaling pathways. In the in vitro system, a unified method for modeling chronic stress conditions was developed and validated, which differs from existing international approaches in that principal component analysis is used to assess the expression of marker genes under the influence of hormonal factors, allowing for highly specific identification of their effects on prostate cancer cells. It was established that in low-grade malignancy cells, the action of chronic stress factors leads to suppression of insulin signaling, whereas in high-grade malignancy cells activation of glycolysis, lactate metabolism, and key components of the insulin/IGF pathway is observed against the background of increased expression of bone matrix regulator genes (osteocalcin, TGF-β), which contributes to increased invasive potential and morphofunctional plasticity. In the in vivo system, using an animal model of Guerin carcinoma, it was shown that prolonged exposure to adrenaline and dexamethasone suppresses antitumor immunity. Chronic stress also led to a significant disruption of mineral homeostasis in tumor-bearing animals, accompanied by hypoglycemia and suppression of the proliferative activity of adherent bone marrow cells. The obtained data indicate a synergistic effect of stress factors at the molecular and systemic levels, contributing to the development of adaptive responses and an increase in tumor malignancy grade. Product Description popup.authors Lesia A. Naleskina Hohol Serhii V. Tetiana V. Borikun Yurii Vitruk Iryna M. Voyeykova Anna O. Pavlova Liubov M. Kunska Liudmyla V. Trembach Nataliia Y. Lukianova Zadvornyi Taras V. Oleksandr M. Mushii Petro A. Virych Andrii Tymoshenko Nataliia I. Fedosova Стаховський Едуард Олександрович Tetiana S. Burda Kyrylo O. Saulenko Tamara P. Kozak popup.nrat_date 2026-01-30 Close