Dataset Information

Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.

ABSTRACT: Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM.

SUBMITTER: Bayona C

PROVIDER: S-EPMC10858941 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.

Bayona Clara C Alza Lía L Ranđelović Teodora T Sallán Marta C MC Visa Anna A Cantí Carles C Ochoa Ignacio I Oliván Sara S Herreros Judit J

Cell death & disease 20240210 2

Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound whic ...[more]

PMID: 38341408

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Project description:BackgroundWith the burgeoning advancements in disease modeling, drug development, and precision medicine, organ-on-a-chip has risen to the forefront of biomedical research. Specifically in tumor research, this technology has exhibited exceptional potential in elucidating the dynamics of metastasis within the tumor microenvironment. Recognizing the significance of this field, our study aims to provide a comprehensive bibliometric analysis of global scientific contributions related to organ-on-a-chip.MethodsPublications pertaining to organ-on-a-chip from 2014 to 2023 were retrieved at the Web of Science Core Collection database. Rigorous analyses of 2305 articles were conducted using tools including VOSviewer, CiteSpace, and R-bibliometrix.ResultsOver the 10-year span, global publications exhibited a consistent uptrend, anticipating continued growth. The United States and China were identified as dominant contributors, characterized by strong collaborative networks and substantial research investments. Predominant institutions encompass Harvard University, MIT, and the Chinese Academy of Sciences. Leading figures in the domain, such as Dr. Donald Ingber and Dr. Yu Shrike Zhang, emerge as pivotal collaboration prospects. Lab on a Chip, Micromachines, and Frontiers in Bioengineering and Biotechnology were the principal publishing journals. Pertinent keywords encompassed Microfluidic, Microphysiological System, Tissue Engineering, Organoid, In Vitro, Drug Screening, Hydrogel, Tumor Microenvironment, and Bioprinting. Emerging research avenues were identified as "Tumor Microenvironment and Metastasis," "Application of organ-on-a-chip in drug discovery and testing" and "Advancements in personalized medicine applications".ConclusionThe organ-on-a-chip domain has demonstrated a transformative impact on understanding disease mechanisms and drug interactions, particularly within the tumor microenvironment. This bibliometric analysis underscores the ever-increasing importance of this field, guiding researchers and clinicians towards potential collaborative avenues and research directions.

Dataset Information

Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.

Publications

Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.

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