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  1. AU="Siles, Francisco"
  2. AU="Song, Sin-Mao"
  3. AU="Yaxuan He"
  4. AU="Wu, Jiaojie"
  5. AU="Tze Kwun Ng"
  6. AU="Leonard L Yeo"

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  1. Article ; Online: Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells.

    Mesén-Porras, Susana / Rojas-Céspedes, Andrea / Molina-Mora, José Arturo / Vega-Baudrit, José / Siles, Francisco / Quiros, Steve / Mora-Rodríguez, Rodrigo

    Cells

    2023  Volume 12, Issue 22

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Sphingolipids/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Cisplatin/pharmacology ; Epirubicin ; Kinetics ; Ceramides/pharmacology ; Ceramides/metabolism ; Paclitaxel/pharmacology
    Chemical Substances Sphingolipids ; Cisplatin (Q20Q21Q62J) ; Epirubicin (3Z8479ZZ5X) ; Ceramides ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2023-11-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12222588
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Thesis: Assessment of the impacts of P and N fertilizers on common beans (Phaseolus vulgaris L.) grown in a volcanic soil in pot and field experiments

    Talavera Siles, Francisco T.

    (Reports and dissertations / Swedish University of Agricultural Sciences, Department of Soil Sciences ; 2)

    1989  

    Author's details Francisco Telémaco Talavera Siles
    Series title Reports and dissertations / Swedish University of Agricultural Sciences, Department of Soil Sciences ; 2
    Collection
    Keywords Gartenbohne ; Vulkanboden ; Phosphatdüngung ; Stickstoffdüngung
    Subject N-Düngung ; Stickstoff ; Phosphate ; Phosphordüngung ; Vulkanischer Boden ; Phaseolus vulgaris ; Schneidebohne ; Schnittbohne ; Speisebohne
    Size 12, 12, 10 S. : graph. Darst.
    Publishing place Uppsala
    Publishing country Sweden
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Uppsala, Univ. of Agricultural Sciences, Diss
    Note Zsfassung in span. Sprache
    HBZ-ID HT003951037
    ISBN 91-576-3984-1 ; 978-91-576-3984-4
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

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  3. Article: Perturbation-Based Modeling Unveils the Autophagic Modulation of Chemosensitivity and Immunogenicity in Breast Cancer Cells.

    Quiros-Fernandez, Isaac / Figueroa-Protti, Lucía / Arias-Arias, Jorge L / Brenes-Cordero, Norman / Siles, Francisco / Mora, Javier / Mora-Rodríguez, Rodrigo Antonio

    Metabolites

    2021  Volume 11, Issue 9

    Abstract: In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-year patient survival rate. ...

    Abstract In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-year patient survival rate. Among the new therapeutic targets that are currently in clinical trials, here, we addressed the association between the regulation of the metabolic process of autophagy and the exposure of damage-associated molecular patterns associated (DAMPs) to immunogenic cell death (ICD), which has not been previously studied. After validating an mCHR-GFP tandem LC3 sensor capacity to report dynamic changes of the autophagic metabolic flux in response to external stimuli and demonstrating that both basal autophagy levels and response to diverse autophagy regulators fluctuate among different cell lines, we explored the interaction between autophagy modulators and chemotherapeutic agents in regards of cytotoxicity and ICD using three different breast cancer cell lines. Since these interactions are very complex and variable throughout different cell lines, we designed a perturbation-based model in which we propose specific modes of action of chemotherapeutic agents on the autophagic flux and the corresponding strategies of modulation to enhance the response to chemotherapy. Our results point towards a promising therapeutic potential of the metabolic regulation of autophagy to overcome chemotherapy resistance by eliciting ICD.
    Language English
    Publishing date 2021-09-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo11090637
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: How many kinds of sclerite? Towards a morphometric classification of gorgoniid microskeletal components.

    Vargas, Sergio / Breedy, Odalisca / Siles, Francisco / Guzman, Hector M

    Micron (Oxford, England : 1993)

    2010  Volume 41, Issue 2, Page(s) 158–164

    Abstract: Gorgoniid octocorals constitute a diverse group of organisms that inhabit a wide range of marine environments. The group is currently defined by the presence of calcareous sclerites that are less than 0.3 mm in length with regularly arranged warts. ... ...

    Abstract Gorgoniid octocorals constitute a diverse group of organisms that inhabit a wide range of marine environments. The group is currently defined by the presence of calcareous sclerites that are less than 0.3 mm in length with regularly arranged warts. Generic and specific classification schemes are based on the presence/absence of different sclerite classes in the sampled specimen as well as the frequency in which each class occurs in the sample. Sclerite classification typically has been difficult because a continuum of sclerite forms is found within and between species. Thus, the use of sclerites for phylogenetic inference and classification is problematic. Herein, we present a methodology to obtain quantitative measurements of large numbers of sclerites and used finite mixture modeling to assess the number of statistically different sclerite classes present in the eastern Pacific octocoral genus Pacifigorgia. We also test the ability of simple neural classifiers (perceptrons) to sort sclerites into the classes traditionally used in octocoral taxonomy. This methodology can be used for other gorgoniids and can be further extended to include shape quantifiers for groups other than those studied here.
    MeSH term(s) Animals ; Anthozoa/chemistry ; Anthozoa/classification ; Calcium Carbonate/analysis ; Image Processing, Computer-Assisted
    Chemical Substances Calcium Carbonate (H0G9379FGK)
    Language English
    Publishing date 2010-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 207808-9
    ISSN 1878-4291 ; 0047-7206 ; 0968-4328
    ISSN (online) 1878-4291
    ISSN 0047-7206 ; 0968-4328
    DOI 10.1016/j.micron.2009.08.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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