Biology subjects

Paquette, B.

Publications and source records attributed to Paquette, B..

3 recordsLinked to original sources

bioRxiv2025

Development of metastases in mice induced by plasma sample collected during radiotherapy in patient with triple-negative breast cancer: Role of Rab4A

The relapse rate in early-stage triple-negative breast cancer (TNBC) is significantly higher than in other breast cancer subtypes. This study assessed the relevance to target RAB4A to prevent the development of metastases that occur after treatment. The ability of cancer cells to invade peritumoral tissue is associated with the expression of membrane-type matrix metalloproteinase-1 on their surface, which is regulated by RAB4A. When RAB4A was downregulated using shRNA in the TNBC cells D2A1 and MDA-MB-231, a significant reduction in the proteolytic activity of MT1-MMP and the invasion capacity of these TNBC cells were measured. Plasma samples from an early-stage TNBC patient, who developed metastases six months after treatment, were collected before radiotherapy and after the fourth radiation dose. Compared to the plasma collected before radiotherapy, the plasma collected during the treatment significantly enhanced the invasiveness of the TNBC cells, as assessed with Boyden chambers. The development of lung metastases was also stimulated when the D2A1 cells were preincubated with this plasma before their i.v. injection in female Balb/c mice. Importantly, these adverse effects of plasma collected during radiotherapy were significantly blocked by downregulating RAB4A. These results highlight the relevance of developing RAB4A inhibitors to prevent the development of metastases occurring after treatment in TNBC patients.

cancer biology↗

bioRxiv2024

Participatory science methods to monitor water quality and ground truth remote sensing of the Chesapeake Bay

Measurements by volunteer scientists using participatory science methods in combination with high resolution remote sensing can improve our ability to monitor water quality changes in highly vulnerable and economically valuable nearshore and estuarine habitats. In the Chesapeake Bay (USA), tidal tributaries are a focus of watershed and shoreline management efforts to improve water quality. The Chesapeake Water Watch program seeks to enhance the monitoring of tributaries by developing and testing methods for volunteer scientists to easily measure chlorophyll, turbidity, and colored dissolved organic matter (CDOM) to inform Bay stakeholders and improve algorithms for analogous remote sensing (RS) products. In the program, trained volunteers have measured surface turbidity using a smartphone app, HydroColor, calibrated with a photographers gray card. In vivo chlorophyll and CDOM fluorescence were assessed in surface samples with hand-held fluorometers (Aquafluor) located at sample processing "hubs" where volunteers drop-off samples for same day processing. In validation samples, HydroColor turbidity and Aquafluor in vivo chlorophyll and CDOM fluorescence were linearly related to standard analytical measures of turbidity, chlorophyll and CDOM, respectively, with R2 values ranging from 0.65 to 0.85. These methods are being used for both repeat sampling at fixed sites of interest and ad-hoc "blitzes" to synoptically sample tributaries all around the Bay in coordination with satellite overpasses. All data is accessible on a public database (serc.fieldscope.org) and can be a resource to monitor long-term trends in the tidal tributaries as well as detect and diagnose causes of events of concern such as algal blooms and storm-induced reductions in water clarity.

ecology↗

bioRxiv2018

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

BackgroundThe receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.\n\nMethodsForty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (1-ENaC), 1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h.\n\nFindingsTreatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of 1-Na,K-ATPase and AQP-5.\n\nInterpretationRAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.\n\nFundingAuvergne Regional Council, Agence Nationale de la Recherche, Direction Generale de lOffre de Soins.\n\nResearch in ContextO_ST_ABSEvidence before this studyC_ST_ABSThe acute respiratory distress syndrome (ARDS), a clinical syndrome of diffuse pulmonary oedema and inflammation, currently lacks effective therapies and is associated with high mortality and morbidity. The degrees of lung epithelial injury and of alveolar fluid clearance (AFC) impairment, as evaluated by plasma levels of soluble receptor for glycation end-products (RAGE), are major prognostic factors in ARDS and potential therapeutic targets for ongoing research. For example, targeting RAGE with recombinant sRAGE or an anti-RAGE monoclonal antibody has proven beneficial in a translational mouse model of acid-induced ARDS.\n\nAdded value of this studyIn a piglet model of acid-induced ARDS, treatment with RAGE antagonist peptide or recombinant sRAGE restored AFC and attenuated the features of lung injury, thereby confirming, in the closest evolutionary model species to humans, previous evidence from rodent models that modulation of RAGE may be a therapeutic option for ARDS. Although this is an important step towards future clinical translation, future studies should assess the best methods to modulate RAGE and further confirm the safety of manipulating this pathway in patients with ARDS.

physiology↗