Publications by authors named "P L Rouzic"

Article Synopsis
  • Microsatellite instability (MSI), often linked to mismatch repair deficiency in colorectal cancer (CRC), leads to numerous noncoding DNA mutations, particularly affecting RNA splicing sites.
  • This research shows that these noncoding mutations happen early in tumor development, even before the cancer cells become mutated in their coding regions, and are associated with altered splicing patterns in mRNA.
  • The altered RNA splicing impacts cellular differentiation and promotes the initiation of MSI CRC, indicating that these noncoding changes are significant for cancer progression before traditional coding mutations occur.
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Background: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy.

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Background & Aims: Next-generation sequencing (NGS) was recently approved by the United States Food and Drug Administration to detect microsatellite instability (MSI) arising from defective mismatch repair (dMMR) in patients with metastatic colorectal cancer (mCRC) before treatment with immune checkpoint inhibitors (ICI). In this study, we aimed to evaluate and improve the performance of NGS to identify MSI in CRC, especially dMMR mCRC treated with ICI.

Methods: CRC samples used in this post hoc study were reassessed centrally for MSI and dMMR status using the reference methods of pentaplex polymerase chain reaction and immunohistochemistry.

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Article Synopsis
  • * The study focused on assessing corticosteroid-binding globulin (CBG) expression in CF patients, using liver and lung samples to understand its potential role in enhancing glucocorticoid therapy.
  • * Results showed increased CBG expression in the liver of CF patients, but decreased levels in the lungs, suggesting that targeting CBG could optimize GC delivery to the inflamed lung tissues in CF.
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Cystic fibrosis (CF) is the most common lethal genetic disease, caused by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations. CF is characterized by an ionic imbalance and thickened mucus, which impair mucociliary clearance and promote bacterial colonization and the establishment of infection/inflammation cycles. However, the origin of this inflammation remains unclear, although microRNAs (miRNAs) are suspected to be involved.

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