Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints

Drug synergy allows reduced dosing, side effects and tolerance. Optimization of drug synergy chemotherapy is fundamental in acute lymphocytic leukemia and other cancers. This study aimed to analyze the pharmacodynamic synergy between the anti-metabolite cytarabine and WEE1 inhibitor adavosertib on acute leukemia cell lines CCRF-CEM and Jurkat. In both cell lines analysis of concentration-inhibition curves of adavosertib-cytarabine combinations and synergy matrixes supported mutually synergistic drug interactions. Overall mean ( ± SD) synergy scores were higher in Jurkat than CCRF-CEM: Jurkat, ZIP 22.51 ± 1.1, Bliss 22.49 ± 1.1, HSA 23.44 ± 1.0, Loewe 14.16 ± 1.2; and, CCRF-CEM, ZIP 9.17 ± 1.9, Bliss 8.13 ± 2.1, HSA 11.48 ± 1.9 and Loewe 4.99 ± 1.8. Jurkat also surpassed CCRF-CEM in high-degree synergistic adavosertib-cytarabine interactions with mean across-models synergy values of ∼89.1% ± 2.9 for 63 nM cytarabine-97 nM adavosertib (91.4% inhibition synergy barometer). Combination sensitivity scores scatter plots confirmed combination’s synergy efficacy. This combined approach permitted identification and prioritization of 63 nM cytarabine-97 nM adavosertib for multiple endpoints analysis. This combination did not affect PBMC viability, while exhibiting Jurkat selective synergy. Immunoblots also revealed Jurkat selective synergistically increased γH2AX phosphorylation, while CDC2 phosphorylation effects were attributed to adavosertib’s WEE1 inhibition. In conclusion, the high synergistic efficacy combination of cytarabine (63 nM) and adavosertib (97 nM) was associated with remarkable alterations in metabolites related to the Krebs cycle in Jurkat. The metabolic pathways and processes are related to gluconeogenesis, amino acids, nucleotides, glutathione, electron transport and Warburg effect. All above relate to cell survival, apoptosis, and cancer progression. Our findings could pave the way for novel biomarkers in treatment, diagnosis, and prognosis of leukemia and other cancers

XVII International Congress of Control Electronics and Telecommunications: "Advanced Science, Technology and Innovation to move towards a new socio-technical system: Sustainable Social Transformation"

Contenido: Approach to the diagnostic of cesarean birth using bio-inspired models. ; Design of a tool in a virtual reality environment to manipulate anatomical models. ; The effect of COVID-19 restrictions on the electricity price forecasting models. ; Depression prevention through artificial intelligence. ; State of the art in Prototypes as complements to the learning of the Colombian Sign Language (LSC). ; A computational proposal for gene expression deterministic analysis in associated disorders to depression and anxiety. ; Evaluation of postural stability from the predictability of the measurement of the center of pressure. ; Psychophysiological Analysis of Sound Stimuli.; Delphi method for the identification of relevant variables in the development of low-power photovoltaic solar projects. ; Socioeconomic impact of a refrigerator powered by a photovoltaic system in La Guajira. ; Energy Efficiency: characteristics that allow the reduction of greenhouse gases in. ; Possibilities for the implementation of a bioreactor from organic waste. ; Energy Potential with Small Hydroelectric Power Plants in Non- interconnected Zones of Colombia. ; Energy Potential in Photovoltaic Solar Solutions in Non-Interconnected Areas of Colombia. ; Photovoltaic system, towards the energy transition from home. ; Blockchain model to increase the transparency of public sector processes. ; Intelligent agricultural irrigation prescription system based on sensor networks and crop modeling. ; Design and implementation of a digital modulation classification system using intelligent algorithms. ; A mobile application proposal to minimize intermediation during agricultural process distribution of products in supply chain. ; Accompanying strategy for the social appropriation of new technologies in vulnerable agricultural communities: case in communities producing Gulupas fruits (Passiflora edulis Sims). ; Predictive model of transparency as an indicator of Public Policies. ; Smart system for recognition of ripening level in blackberry fruits. ; Project-based learning as an alternative methodology for technological education in electronics. ; Design and construction of an automated system for N. ; Four bar mechanisms (FBM) and their Software-Based applications: a reviewFT aquaponic culture of Red Carp and Crespa Lettuce. ; Intelligent search implementation for the construction of states of the art: a python application. ; Indoor and Outdoor propagation models on 5G environments: state of the art. ;The electronic detection of offenders (DOO) in the District Secretary of mobility of Bogotá: a step forward in the configuration of the concept of digital citizenship in Colombia. ; Monitoring through ICT of Mobility: technological collaborative feature to incorporate IoT in a Smart City. ; Characterization model of asphalt mixtures using digital image processing. ; Review: identification of diseases and/or pests in fruit trees through image processing techniques and artificial intelligence. ; VRS applicated to Nasa Yuwe language. ; Application of Pix2Pix for edge reconstruction in images. ; Brushless DC Motor Control System for Active Myoelectric Prosthesis. ; Implementation of a Water Conductivity Measuring System. ; 2 DOF robot programmed with MatLab® (guide and Peter Corke) and Arduino uno for writing alphabetical characters. ; Simulator of the behavior of the center of mass in a quadruped robot. ; Biomimetic prototype for flapping movement of batsContent: Contenido: Approach to the diagnostic of cesarean birth using bio-inspired models. ; Design of a tool in a virtual reality environment to manipulate anatomical models. ; The effect of COVID-19 restrictions on the electricity price forecasting models. ; Depression prevention through artificial intelligence. ; State of the art in Prototypes as complements to the learning of the Colombian Sign Language (LSC). ; A computational proposal for gene expression deterministic analysis in associated disorders to depression and anxiety. ; Evaluation of postural stability from the predictability of the measurement of the center of pressure. ; Psychophysiological Analysis of Sound Stimuli.; Delphi method for the identification of relevant variables in the development of low-power photovoltaic solar projects. ; Socioeconomic impact of a refrigerator powered by a photovoltaic system in La Guajira. ; Energy Efficiency: characteristics that allow the reduction of greenhouse gases in. ; Possibilities for the implementation of a bioreactor from organic waste. ; Energy Potential with Small Hydroelectric Power Plants in Non- interconnected Zones of Colombia. ; Energy Potential in Photovoltaic Solar Solutions in Non-Interconnected Areas of Colombia. ; Photovoltaic system, towards the energy transition from home. ; Blockchain model to increase the transparency of public sector processes. ; Intelligent agricultural irrigation prescription system based on sensor networks and crop modeling. ; Design and implementation of a digital modulation classification system using intelligent algorithms. ; A mobile application proposal to minimize intermediation during agricultural process distribution of products in supply chain. ; Accompanying strategy for the social appropriation of new technologies in vulnerable agricultural communities: case in communities producing Gulupas fruits (Passiflora edulis Sims). ; Predictive model of transparency as an indicator of Public Policies. ; Smart system for recognition of ripening level in blackberry fruits. ; Project-based learning as an alternative methodology for technological education in electronics. ; Design and construction of an automated system for N. ; Four bar mechanisms (FBM) and their Software-Based applications: a reviewFT aquaponic culture of Red Carp and Crespa Lettuce. ; Intelligent search implementation for the construction of states of the art: a python application. ; Indoor and Outdoor propagation models on 5G environments: state of the art. ;The electronic detection of offenders (DOO) in the District Secretary of mobility of Bogotá: a step forward in the configuration of the concept of digital citizenship in Colombia. ; Monitoring through ICT of Mobility: technological collaborative feature to incorporate IoT in a Smart City. ; Characterization model of asphalt mixtures using digital image processing. ; Review: identification of diseases and/or pests in fruit trees through image processing techniques and artificial intelligence. ; VRS applicated to Nasa Yuwe language. ; Application of Pix2Pix for edge reconstruction in images. ; Brushless DC Motor Control System for Active Myoelectric Prosthesis. ; Implementation of a Water Conductivity Measuring System. ; 2 DOF robot programmed with MatLab® (guide and Peter Corke) and Arduino uno for writing alphabetical characters. ; Simulator of the behavior of the center of mass in a quadruped robot. ; Biomimetic prototype for flapping movement of bat