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Recent Submissions

Access status: Embargo ,
AXL signaling pathway: biology and therapeutic perspectives for bladder cancer
(Nazarbayev University School of Medicine, 2025-06) Malikova, Ilona; Tulchinsky, Eugene
Bladder cancer is one of the most common cancers in the world, and the overall survival rate for patients with metastatic bladder cancer is low. One of the main risk factors of bladder cancer is age, which makes it a growing concern in developed countries with a high proportion of the elderly population. Also, Schistosoma haematobium-infected individuals are at high risk of bladder cancer development as a complication of schistosomiasis in countries across Africa and the Middle East. Therefore, the demand for more efficient treatment approaches for bladder cancer, especially its advanced forms, is high, and there is an unmet need to find new targets for therapies against bladder cancer. AXL is a TAM family receptor tyrosine kinase that is overexpressed in various cancers. AXL signalling is important for most of the cancer hallmarks, such as proliferation, survival, invasion, epithelial-mesenchymal transition, and angiogenesis. According to the analysis of publicly available databases, high expression of AXL is associated with poor survival of bladder cancer patients. The aim of the work was to characterize the molecular effects of AXL inhibition by its small molecule inhibitors. The experiments primarily focused on the type 1 small molecule RTK inhibitor TP-0903, which is currently undergoing clinical trials for the treatment of various solid cancers. The obtained results show that AXL and its ligand GAS6 are co-expressed in bladder cancer cell lines with a quasi-mesenchymal or mesenchymal phenotype. TP-0903 prevents ligand-dependent AXL phosphorylation, while its prolonged application results in GAS6-independent non-canonical phosphorylation of AXL. In contrast, type 2 small molecule RTK inhibitor LDC1267 has no such effect. I found that extended treatment of cells with TP-0903 increases the level of ROS in bladder cancer cells, and TP-0903-induced AXL phosphorylation within the kinase domain at Y702 and Y703 is ROS-dependent. In contrast, AXL phosphorylation at Y779, a tyrosine residue responsible for interaction with some adaptor proteins, is ROS-independent and can occur due to AXL heterodimerization with other RTK, such as ERBB2. Also, I show that TP-0903 has a dramatic effect on the kinome in bladder cancer cells. Overall, the results of this work demonstrate that the type 1 small molecule RTK inhibitor TP-0903 induces AXL phosphorylation that is independent of GAS6. This unexpected effect relies on ROS. Consequently, the application of TP-0903 rewires signalling in bladder cancer cells, and this finding should be taken into consideration when AXL-targeted therapeutics are applied in clinical settings.
Access status: Embargo ,
Development and Application of Capacitance Resistance Models (CRMs) for Enhanced Oil Recovery Processes
(Nazarbayev University School of Mining and Geosciences, 2026-02-12) Zhanabayeva, Meruyet; Pourafshary, Peyman; Soroush, Mohammad; Madani, Nasser
Evaluating interwell connectivity provides critical insights for reservoir management, including the identification of flow conduits, barriers, and injection-production imbalances. Injection and production rates contain valuable information about connectivity, and various methods have been developed to extract this information. Among them, the Capacitance Resistance Models (CRMs) have been successfully applied in numerous waterflooding projects. CRM is based on a linear productivity index and assumes a pseudo–steady-state flow regime for slightly compressible fluids. However, its application to gas injection projects is limited due to the high compressibility of gas and its strong dependence on pressure. Therefore, it is essential to identify the range of fluid and reservoir conditions under which the CRM can still yield reliable results. The first objective of this work is to determine the applicability limits of the conventional CRM for immiscible gas flooding by conducting a sensitivity analysis on its predictive accuracy. Various reservoir and fluid properties—such as temperature, pressure, viscosity, density, and heterogeneity—were tested to evaluate their impact on CRM performance. Unlike water, gas exhibits significant compressibility, leading to nonlinear flow behavior, especially under changing pressure conditions. Consequently, the second objective of this study is to modify the conventional CRM to account for gas compressibility and nonlinear interwell flow dynamics during immiscible gas injection. The results indicate that CRM accuracy decreases in low-permeability reservoirs. Additionally, the model performs worse in light oil systems compared to heavy oil under immiscible gas injection. High pressure and low temperature conditions, which can lead the gas state be closer to liquid state, were found to improve CRM performance. Temperature variations had a more pronounced effect on CRM results during gas injection than pressure variations. Furthermore, by incorporating a pseudo-pressure term into the CRM framework, this study demonstrates improved accuracy in evaluating reservoir performance under immiscible gas flooding. The third objective extends the application of CRM to enhanced oil recovery (EOR) processes such as polymer flooding. By modifying CRM to account for viscosity-related changes in mobility ratio, the model showed improved performance in analyzing polymer injection. A synthetic cartesian reservoir models and a benchmark case study are evaluated to illustrate the effectiveness of the proposed approach. In conclusion, applying the conventional CRM in gas injection cases may result in misleading estimates of interwell connectivity and inaccurate rate predictions. The improved CRM framework proposed in this study enable better characterization of gas flow behavior and its influence on reservoir dynamics, supporting more effective reservoir management decisions.
Access status: Open Access ,
Experimental and Numerical Simulation Studies of the Zwitterionic Polymer for Enhanced Oil Recovery
(Nazarbayev University School of Engineering and Digital Sciences, 2026) Karimov, Damir; Nuraje, Nurxat; Pourafshary, Peyman; Hashmet, Muhammad
This study presents a comprehensive investigation into the synthesis, characterization, and performance evaluation of zwitterionic polymers for enhanced oil recovery (EOR) applications. Three zwitterionic copolymers, which contains positively and negatively charged groups, designated as zPAM 1, zPAM 2, and zPAM 3, were synthesized and subjected to a series of analytical techniques to validate their successful synthesis and assess their properties. Fourier-transform infrared (FTIR) spectroscopy confirmed successful synthesis through characteristic peaks of N–H (3319–3338 cm⁻¹), C=O (1639–1662 cm⁻¹), and sulfonate groups (1113–1189 cm⁻¹). Proton nuclear magnetic resonance (1H NMR) spectra further verified the incorporation of zwitterionic units into the polymer backbone. Dynamic light scattering (DLS) revealed high molecular weights ranging from 598 to 734 kDa, confirming their suitability for EOR applications. Scanning electron microscopy (SEM) showed distinct morphologies, with zPAM 1 and zPAM 2 exhibiting highly ordered network structures conducive to enhanced stability and mechanical integrity. Rheological experiments demonstrated typical shear-thinning behavior across all copolymers. Among them, zPAM 1 exhibited the highest viscosity values, with a 30 % viscosity increase as salinity rose from 100,000 to 200,000 ppm and a 60% viscosity loss as temperature increased from 25 °C to 60 °C. Coreflooding experiments, conducted at 63 °C and 200,000 ppm salinity using a polymer concentration of 1000 ppm, revealed that zPAM 1 achieved a total oil recovery factor of 56.5%, compared to 52.3% for commercial hydrolyzed polyacrylamide (HPAM). The higher pressure drop observed during postflush indicated stronger mobility control for zPAM 1. The superior EOR performance of zPAM 1 is attributed to its optimized molecular architecture, enhanced salinity tolerance, and favorable viscoelastic behavior arising from its DMAPMAPS-based zwitterionic structure. These findings underscore the importance of molecular design and structural composition in influencing the rheological behavior and performance of zwitterionic polymers in EOR applications. The insights gained from this study contribute to a deeper understanding of zwitterionic polymers' potential for enhancing oil recovery efficiency and sustainability, discovering new ways for further research and optimization in this field.
Access status: Metadata only ,
Imaging Flow Cytometry of Multi-Nuclearity
(Springer Verlag, 2023-04-20) Vorobjev, Ivan; Bekbayev, Sultan; Temirgaliyev, Adil; Tlegenova, Madina; Barteneva, Natasha; School of Sciences and Humanities; Department of Biology
Multi-nuclearity is a common feature for cells in different cancers. Also, analysis of multi-nuclearity in cultured cells is widely used for evaluating the toxicity of different drugs. Multi-nuclear cells in cancer and under drug treatments form from aberrations in cell division and/or cytokinesis. These cells are a hallmark of cancer progression, and the abundance of multi-nucleated cells often correlates with poor prognosis. The use of standard bright field or fluorescent microscopy to analyze multi-nuclearity at the quantitative level is laborious and can suffer from user bias. Automated slide-scanning microscopy can eliminate scorer bias and improve data collection. However, this method has limitations, such as insufficient visibility of multiple nuclei in the cells attached to the substrate at low magnification. Since quantification of multi-nuclear cells using microscopic methods might be difficult, imaging flow cytometry (IFC) is a method of choice for this. We describe the experimental protocol for the preparation of the samples of multi-nucleated cells from the attached cultures and the algorithm for the analysis of these cells by IFC. Images of multi-nucleated cells obtained after mitotic arrest induced by taxol, as well as cells obtained after cytokinesis blockade by cytochalasin D treatment, can be acquired at a maximal resolution of IFC. We suggest two algorithms for the discrimination of single-nucleus and multi-nucleated cells. The advantages and disadvantages of IFC analysis of multi-nuclear cells in comparison with microscopy are discussed.
Access status: Metadata only ,
Mitochondrial, metabolic and bioenergetic adaptations drive plasticity of colorectal cancer cells and shape their chemosensitivity
(Nazarbayev University, 2025-12-01) Nikolai; Barlev
The extent of mitochondrial heterogeneity and the presence of mitochondrial archetypes in cancer remain unknown. Mitochondria play a central role in the metabolic reprogramming that occurs in cancer cells. This process adjusts the activity of metabolic pathways to support growth, proliferation, and survival of cancer cells. Using a panel of colorectal cancer (CRC) cell lines, we revealed extensive differences in their mitochondrial composition, suggesting functional specialisation of these organelles. We differentiated bioenergetic and mitochondrial phenotypes, which point to different strategies used by CRC cells to maintain their sustainability. Moreover, the efficacy of various treatments targeting metabolic pathways was dependent on the respiration and glycolysis levels of cancer cells. Furthermore, we identified metabolites associated with both bioenergetic profiles and cell responses to treatments. The levels of these molecules can be used to predict the therapeutic efficacy of anti-cancer drugs and identify metabolic vulnerabilities of CRC. Our study indicates that the efficacy of CRC therapies is closely linked to mitochondrial status and cellular bioenergetics.