0000000000717634
AUTHOR
Pierre-simon Bellaye
showing 21 related works from this author
Optimising experimental research in respiratory diseases: an ERS statement
2018
Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numb…
Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages
2020
free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupl…
GARP: A Key Target to Evaluate Tumor Immunosuppressive Microenvironment
2021
Simple Summary Tumors are not only composed of cancer cells but also of various infiltrating cells constituting the tumor microenvironment (TME); all these cells produce growth factors which contribute to tumor progression and invasiveness. Among them, transforming growth factor-β1 (TGF-β1) has been shown to be a potent immunosuppressive cytokine favoring cell proliferation and invasion and to be associated with resistance to anticancer treatments. Glycoprotein-A repetition predominant (GARP) plays a critical role in the activation of TGF-β1 and has been shown to be expressed at the membrane of cancer cells and also of regulatory T cells and platelets in the TME. An increased GARP expressio…
The small heat-shock protein α B-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis
2014
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is stron…
Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties
2021
International audience; Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based o…
The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT
2021
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients’ outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative…
Site-specific near-infrared fluorescent labelling of proteins on cysteine residues with meso -chloro-substituted heptamethine cyanine dyes
2018
International audience; Near-infrared (NIR) fluorescence imaging is a promising new medical imaging modality. Associated with a targeting molecule, NIR fluorophores can accumulate selectively in tissues of interest and become valuable tools for the diagnosis and therapy of various pathologies. To facilitate the design of targeted NIR imaging agents, it is important to identify simple and affordable fluorescent probes, allowing rapid labelling of biovectors such as proteins, ideally in a site-specific manner. Here, we demonstrate that heptamethine cyanine based fluorophores, such as IR-783, that contain a chloro-cyclohexyl moiety within their polymethine chain can react selectively, at neutr…
Procollagen C-Proteinase Enhancer 1 (PCPE-1) is a marker of myocardial fibrosis and impaired cardiac function in a murine model of pressure overload
2021
Abstract(1)AimsProcollagen C-proteinase enhancer 1 (PCPE-1) is an extracellular matrix protein and a major regulator of fibrillar collagen biosynthesis. Previous work has shown that its abundance is often increased in the context of tissue repair and fibrosis. The present study was designed to evaluate its potential as a biomarker of myocardial interstitial fibrosis (MIF), a well-established pathogenic pathway leading to heart failure.(2)Methods and ResultsCardiac fibrosis was induced in rats using an optimized model of chronic pressure overload triggered by angiotensin II and Nω-nitro-L-arginine methyl ester (L-NAME). All treated animals suffered from heart hypertrophy and the increase in …
Heat shock protein: a hot topic in idiopathic pulmonary fibrosis
2017
HSP90 inhibition could be an exciting new treatment strategy for IPF http://ow.ly/HfKY306uvxw
Modular Assembly of Multimodal Imaging Agents through an Inverse Electron Demand Diels–Alder Reaction
2019
International audience; The combination of two imaging probes on a same biomolecule gives access to targeted bimodal imaging agents that can provide more accurate diagnosis, complementary information, or that may be used in different applications, such as PET imaging and fluorescence imagingassisted surgery. In this study, we demonstrate that dichlorotetrazine, a small, commercially available compound, can be used as a modular platform to easily assemble various imaging probes. Doubly-labeled tetrazines can then be conjugated to a protein through a biorthogonal IEDDA reaction. A series of difunctionalized tetrazine compounds containing various chelating agents and fluorescent dyes was synth…
Role of the small heat shock protein alphaB-crystallin in pulmonary fibrosis and its implication in the signaling pathway of the Transforming Growth …
2013
Idiopathic pulmonary fibrosis (IPF) has no effective current treatment. It is characterized by a sub-pleural onset and the presence of myofibroblasts, responsible for the excessive extracellular matrix synthesis. Transforming Growth Factor (TGF)-β1 is considered as the major profibrotic cytokine. Its signaling pathway occurs through the Smads proteins, including Smad4. TGF-β1 allows the differentiation of lung fibroblasts and epithelial and mesothelial cells into myofibroblasts. AB-crystallin is a small heat shock protein overexpressed in liver, renal and vascular fibrosis and can be induced by TGF-β1. In this study, we assessed the role of αB-crystallin in pleural and pulmonary fibrosis. W…
Nanofitins targeting heat shock protein 110: an innovative immunotherapeutic modality in cancer.
2021
The presence of an inactivating heat shock protein 110 (HSP110) mutation in colorectal cancers has been correlated with an excellent prognosis and with the ability of HSP110 to favor the formation of tolerogenic (M2-like) macrophages. These clinical and experimental results suggest a potentially powerful new strategy against colorectal cancer: the inhibition of HSP110. In this work, as an alternative to neutralizing antibodies, Nanofitins (scaffold ~7 kDa proteins) targeting HSP110 were isolated from the screening of a synthetic Nanofitin library, and their capacity to bind (immunoprecipitation, biolayer interferometry) and to inhibit HSP110 was analyzed in vitro and in vivo. Three Nanofiti…
Positron Emission Tomography Imaging of Neurotensin Receptor-Positive Tumors with 68 Ga-Labeled Antagonists: The Chelate Makes the Difference Again
2021
Neurotensin receptor 1 (NTS1) is involved in the development and progression of numerous cancers, which makes it an interesting target for the development of diagnostic and therapeutic agents. A small molecule NTS1 antagonist, named [177Lu]Lu-IPN01087, is currently evaluated in phase I/II clinical trials for the targeted therapy of neurotensin receptor-positive cancers. In this study, we synthesized seven compounds based on the structure of NTS1 antagonists, bearing different chelating agents, and radiolabeled them with gallium-68 for PET imaging. These compounds were evaluated in vitro and in vivo in mice bearing a HT-29 xenograft. The compound [68Ga]Ga-bisNODAGA-16 showed a promising biod…
Cytotoxic glycosides from the roots of Weigela x “Bristol Ruby”
2019
International audience; Seven oleanane-type glycosides were extracted and isolated by various chromatographic methods from the roots of Weigela x "Bristol Ruby" (1-7), six previously undescribed (1-6) and a known one (7). Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESIMS). Selected triterpenoid glycosides (1-3, 6, 7) displayed a good cytotoxic activity against a mouse colon cancer cell line CT26.
Small heat shock proteins and the cytoskeleton: an essential interplay for cell integrity?
2012
Abstract The cytoskeleton is a highly complex network of three major intracellular filaments, microfilaments (MFs), microtubules (MTs) and intermediate filaments (IFs). This network plays a key role in the control of cell shape, division, functions and interactions in animal organs and tissues. Dysregulation of the network can contribute to numerous human diseases. Although small HSPs (sHSPs) and in particular HSP27 (HSPB1) or αB-crystallin (HSPB5) display a wide range of cellular properties, they are mostly known for their ability to protect cells under stress conditions. Mutations in some sHSPs have been found to affect their ability to interact with cytoskeleton proteins, leading to IF a…
Heat shock proteins in fibrosis and wound healing: Good or evil?
2014
Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP…
Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation
2013
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation. Transition of epithelial/mesothelial cells into myofibroblasts [epithelial-to-mesenchymal transition (EMT)] occurs under the influence of transforming growth factor (TGF)-β1, with Snail being a major transcription factor. We study here the role of the heat-shock protein HSP27 in fibrogenesis and EMT. In vitro, we have up- and down-modulated HSP27 expression in mesothelial and epithelial cell lines and studied the expression of different EMT markers induced by TGF-β1. In vivo, we inhibited HSP27 with the antisense oligonucleotide OGX-427 (in phase II clinical trials as anticancer agent)…
Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the …
2021
A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [111In] indium and studied in vivo. The developed monomolecular multimodal imaging probe (MOMIP) is water-soluble and chemically and photochemically stable, emits in the near infrared (NIR) region (734 nm in aqueous media), and displays a goo…
Extracellular Heat Shock Proteins as Therapeutic Targets and Biomarkers in Fibrosing Interstitial Lung Diseases.
2021
Interstitial lung diseases (ILDs) include a large number of diseases and causes with variable outcomes often associated with progressive fibrosis. Although each of the individual fibrosing ILDs are rare, collectively, they affect a considerable number of patients, representing a significant burden of disease. Idiopathic pulmonary fibrosis (IPF) is the typical chronic fibrosing ILD associated with progressive decline in lung. Other fibrosing ILDs are often associated with connective tissues diseases, including rheumatoid arthritis-ILD (RA-ILD) and systemic sclerosis-associated ILD (SSc-ILD), or environmental/drug exposure. Given the vast number of progressive fibrosing ILDs and the dispariti…
Dual Cherenkov Radiation-Induced Near-Infrared Luminescence Imaging and Photodynamic Therapy toward Tumor Resection
2020
International audience; Cherenkov radiation (CR), the blue light seen in nuclear reactors, is emitted by some radiopharmaceuticals. This study showed that (1) a portion of CR could be transferred in the region of the optical spectrum, where biological tissues are most transparent: as a result, upon radiance amplification in the near-infrared window, the detection of light could occur twice deeper in tissues than during classical Cherenkov luminescence imaging and (2) Cherenkov-photodynamic therapy (CR-PDT) on cells could be achieved under conditions mimicking unlimited depth using the CR-embarked light source, which is unlike standard PDT, where light penetration depth is limited in biologi…
Le FGF-9 inhibe la fibrose pleurale viro-induite chez la souris
2015
La fibrose pulmonaire idiopathique (FPI) est une pathologie mortelle, predominante en zone sous-pleurale. Elle serait en partie due a une reactivation des voies impliquees dans le developpement pulmonaire. Le Fibroblast Growth Factor-9 (FGF-9) est reexprime par les cellules mesotheliales lors de la FPI. Nous avons determine l’effet de la surexpression de FGF-9 par les cellules mesotheliales chez la souris. Des souris C56/Bl6 ont recu une injection intrapleurale unique de serum physiologique (groupe Phy) ou un adenovirus recombine exprimant le FGF-9 humain (groupe AdFGF-9) ou un adenovirus controle (groupe Adcont), a la concentration de 1 × 108 pfu/mL. Les souris ont ete sacrifiees a j3, j5,…