PhD Scientific Days 2023

Budapest, 22-23 June 2023

Pathology - Posters C

Morphological and molecular-biological Characteristics of Glioblastoma in Male Rats with Different Resistance to Hypoxia

Dzhalilova D.Sh.1, Mkhitarov V.A.2, Tsvetkov I.S.3, Khochansky D.N.4, Makarova O.V.5
1 Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Avtsyn Research Institute of Human Morphology, Moscow
2 Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Avtsyn Research Institute of Human Morphology, Moscow
3 Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Avtsyn Research Institute of Human Morphology, Moscow
4 Heart and Vascular Centre, Semmelweis University, Faculty of medicine, Budapest
5 Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Avtsyn Research Institute of Human Morphology, Moscow

Text of the abstract

Introduction
Hypoxia is a major pathogenetic factor in many cancers. Individual resistance to suboptimal oxygen availability is subject to broad variation and its possible role in tumorigenesis remains underexplored.
Aims
To characterize the morphological and molecular-biological features of glioblastoma progression in male tolerant and susceptible to hypoxia Wistar rats.
Method
Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed ‘tolerant to hypoxia’ (n=24), ‘normal’, and ‘susceptible to hypoxia’ (n=13). The ‘normal’ group was excluded from subsequent experiments. One month later, the animals underwent inoculation with rat glioblastoma 101.8 followed by monitoring of survival, body weight dynamics and neurological symptoms. The animals were sacrificed on post inoculation days 11 (subgroup 1) and 15 (subgroup 2). Relative vascular counts, necrosis areas and Ki-67 index were assessed microscopically; tumor volumes were determined by 3D reconstruction from histological images; serum levels of HIF-1α, IL-1β, and TNFα were determined by ELISA.
Results
None of the tolerant to hypoxia animals died of the disease during observation period, cf. 85% survival on day 11 and 55% survival on day 15 in the susceptible group. On day 11, proliferative activity of the tumors in the tolerant animals was higher compared with the susceptible group. On day 15, proliferative activity, necrosis area and volume of the tumors in the tolerant to hypoxia animals were higher compared with the susceptible group. ELISA revealed elevated levels of IL-1β in the susceptible animals on day 15 and elevated levels of HIF-1α in the tolerant animals on day 15.
Conclusion
Specific features of glioblastoma 101.8 progression in tolerant and susceptible to hypoxia rats, including survival and the rates of tumor growth and necrosis, can become the basis of new personalized approaches for cancer diseases treatment in accordance to individual hypoxia resistance.
Funding
The work was carried out and financed under budgetary topic 122030200530-6 “Cellular and molecular biological mechanisms of inflammation in the development of socially significant human diseases”.