Predicting Cancer Chemosensitivity Based on Intensity/Distribution Profiles of Cells Loaded with a Fluorescent Sphingolipid Analogue

Quiros-Fernandez, Isaac; Molina-Mora, José Arturo; Kop-Montero, M; Salas-Hidalgo, E; Mora-Rodriguez, RA

doi:10.1109/iwobi.2018.8464199

Cited by 2 publications

(4 citation statements)

References 19 publications

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“…The methodology described here is based on our previous publications (Quiros et al (2018) and Molina et al ( 2018)); however, we adapted the procedure to our cancer cell line [43,44].…”

Section: Methodsmentioning

confidence: 99%

“…Next, we propose a network topology of the SL pathway for the A549 lung cancer cell line (Figure 4) based on the metabolism of the SM-BOD probe that we described in previous studies [44,45]; the green boxes represent the fluorescent metabolites, the white ones indicate loss of fluorescence and magenta boxes are the enzymes-inhibitors of the SL pathway. We coupled this model topology of the autophagic process with its main steps enclosed in dotted circles (P: phagophore, AP: autophagosome, and AL: autophagolysosome).…”

Section: A Gmm Model Of Heterogeneity Profiles Of the Metabolic Fate ...mentioning

confidence: 99%

“…Afterward, we constructed and fitted a dynamic mathematical model based on the metabolism kinetics of the SM-BOD probe to simulate the total fluorescent level changes upon perturbations. We combined the ordinary differential equations (ODE) to infer the metabolism of SM-BOD with Gaussian Mixture Modeling (GMM) to map how the chemotherapy is sensed in the SL pathway based on cell heterogeneity profiles [43] and a fuzzy logic model to derive rules for making predictions about drug combinations to enhance cell death and overcome thereby the drug resistance [44,45].…”

Section: Introductionmentioning

confidence: 99%

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Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells

Mesén-Porras,

Rojas-Céspedes,

Molina-Mora

et al. 2023

Cells

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Tumor heterogeneity leads to drug resistance in cancer treatment with the crucial role of sphingolipids in cell fate and stress signaling. We analyzed sphingolipid metabolism and autophagic flux to study chemotherapeutic interactions on the A549 lung cancer model. Loaded cells with fluorescent sphingomyelin analog (BODIPY) and mCherry-EGFP-LC3B were used to track autophagic flux and assess cytotoxicity when cells are exposed to chemotherapy (epirubicin, cisplatin, and paclitaxel) together with sphingolipid pathway inhibitors and autophagy modulators. Our cell model approach employed fluorescent sphingolipid biosensors and a Gaussian Mixture Model of cell heterogeneity profiles to map the influence of chemotherapy on the sphingolipid pathway and infer potential synergistic interactions. Results showed significant synergy, especially when combining epirubicin with autophagy inducers (rapamycin and Torin), reducing cell viability. Cisplatin also synergized with a ceramidase inhibitor. However, paclitaxel often led to antagonistic effects. Our mapping model suggests that combining chemotherapies with autophagy inducers increases vesicle formation, possibly linked to ceramide accumulation, triggering cell death. However, the in silico model proposed ceramide accumulation in autophagosomes, and kinetic analysis provided evidence of sphingolipid colocalization in autophagosomes. Further research is needed to identify specific sphingolipids accumulating in autophagosomes. These findings offer insights into potential strategies for overcoming chemotherapy resistance by targeting the sphingolipid pathway.

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“…The methodology described here is based on our previous publications (Quiros et al (2018) and Molina et al ( 2018)); however, we adapted the procedure to our cancer cell line [43,44].…”

Section: Methodsmentioning

confidence: 99%

Section: A Gmm Model Of Heterogeneity Profiles Of the Metabolic Fate ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells

Mesén-Porras,

Rojas-Céspedes,

Molina-Mora

et al. 2023

Cells

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show abstract

“…Examples of some of the most relevant contributions within this track are the works of Brenes-Guillén et al [7] on a systems biology approach to investigate control targets of intracellular calcium transients, Vargas et al [8] on feature selection based on chromosomal regions alterations, Quiros-Fernandez et al [9] on predicting cancer chemosensitivity based on intensity/distribution profiles of cells, or Campos-Sánchez and Sandoval-Carvajal [10] on the detection of endogenous retrovirus-derived transcripts in human testis.…”

Section: Biocomputation and Systems Biology Trackmentioning

confidence: 99%

2018 IEEE International Work Conference on Bioinspired Intelligence (IWOBI): Conference Report

Crespo-Mariño

2019

Biomimetics

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The International Work Conference on Bioinspired Intelligence (IWOBI) is an annual event that comprises both an international peer-reviewed scientific conference and a set of workshops and other activities in order to foster the research abilities and expertise of young researchers in the field of bioinspired intelligence. IWOBI 2018 has been characterized by a strong transdisciplinary component. The main conference themes were at the intersection between classical engineering disciplines and computer science, and the life and health sciences. This was motivated by the scientific environment that defines research that is being conducted in Costa Rica. Even though IWOBI is an international event, it was very important for the local organizing committee to focus on knowledge areas that were considered of special interest to Costa Rican researchers and to students looking to start their scientific careers. With such great expectations, IWOBI 2018 has been the first IWOBI conference in history to have parallel tracks. In addition to a regular track, a biocomputation and related techniques track was developed, as well as another one devoted to high-performance computing (HPC) systems applications for life and health sciences applications. Workshops were another important resource developed within IWOBI 2018. They were considered a very important tool in order to foster and train young researchers within the country and they are a very valuable chance to establish direct networking with elite researchers from different countries and research interests. IWOBI 2018 was the first IWOBI conference that implemented real and effective workshops. There were two workshops, one of them devoted to COPASI software and the other one focused on the use of the message passing interface (MPI) parallel programming library.

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Predicting Cancer Chemosensitivity Based on Intensity/Distribution Profiles of Cells Loaded with a Fluorescent Sphingolipid Analogue

Cited by 2 publications

References 19 publications

Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells

Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells

2018 IEEE International Work Conference on Bioinspired Intelligence (IWOBI): Conference Report

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