Publications by authors named "C Basset"

81 Publications

Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

EMBO Mol Med 2021 May 25:e13502. Epub 2021 May 25.

Centre de Recherches en Cancérologie de Toulouse, Inserm, CNRS, Université de Toulouse, Toulouse, France.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP , with a selective decrease of C36:2 PI-3,4,5-P . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution.
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http://dx.doi.org/10.15252/emmm.202013502DOI Listing
May 2021

Dual RNAseq highlights the kinetics of skin microbiome and fish host responsiveness to bacterial infection.

Anim Microbiome 2021 May 7;3(1):35. Epub 2021 May 7.

Ifremer, IRD, Institut Louis-Malardé, Univ Polynésie Française, EIO, F-98719 Taravao, Tahiti, Polynésie Française.

Background: Tenacibaculum maritimum is a fish pathogen known for causing serious damage to a broad range of wild and farmed marine fish populations worldwide. The recently sequenced genome of T. maritimum strain NCIMB 2154 provided unprecedented information on the possible molecular mechanisms involved in the virulence of this species. However, little is known about the dynamic of infection in vivo, and information is lacking on both the intrinsic host response (gene expression) and its associated microbiota. Here, we applied complementary omic approaches, including dual RNAseq and 16S rRNA gene metabarcoding sequencing using Nanopore and short-read Illumina technologies to unravel the host-pathogen interplay in an experimental infection system using the tropical fish Platax orbicularis as model.

Results: We showed that the infection of the host is characterised by an enhancement of functions associated with antibiotic and glucans catabolism functions but a reduction of sulfate assimilation process in T. maritimum. The fish host concurrently displays a large panel of immune effectors, notably involving innate response and triggering acute inflammatory response. In addition, our results suggest that fish activate an adaptive immune response visible through the stimulation of T-helper cells, Th17, with congruent reduction of Th2 and T-regulatory cells. Fish were, however, largely sensitive to infection, and less than 25% survived after 96 hpi. These surviving fish showed no evidence of stress (cortisol levels) or significant difference in microbiome diversity compared with controls at the same sampling time. The presence of T. maritimum in resistant fish skin and the total absence of any skin lesions suggest that these fish did not escape contact with the pathogen, but rather that some mechanisms prevented pathogens entry. In resistant individuals, we detected up-regulation of specific immune-related genes differentiating resistant individuals from controls at 96 hpi, which suggests a possible genomic basis of resistance, although no genetic variation in coding regions was found.

Conclusion: Here we focus in detail on the interplay between common fish pathogens and host immune response during experimental infection. We further highlight key actors of defence response, pathogenicity and possible genomic bases of fish resistance to T. maritimum.
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http://dx.doi.org/10.1186/s42523-021-00097-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106148PMC
May 2021

Atrial natriuretic peptide differentiates between primary submandibular gland squamous cell carcinoma and oral squamous cell carcinoma: preliminary data.

J Biol Regul Homeost Agents 2021 Mar-Apr;35(2):729-733

Department of Biomedicine, Neuroscience and Advanced Diagnostic, Bi.N.D, School of Medicine, Institute of Anatomy and Histology, University of Palermo, Palermo, Italy.

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http://dx.doi.org/10.23812/21-12-LDOI Listing
May 2021

Dynamic Energy Budget model suggests feeding constraints and physiological stress in black-lip pearl oysters, 5 years post mass-mortality event.

Mar Pollut Bull 2021 Jun 13;167:112329. Epub 2021 Apr 13.

IFREMER, IRD, Institut Louis-Malardé, Univ Polynésie française, EIO, F-98719 Taravao, Tahiti, French Polynesia.

Mass-mortality events of marine species can disturb the structure of communities. While identifying the causes of mass-mortality events is crucial for implementing recovery strategies, monitoring is challenging in remote locations. Black-lip pearl oysters (Pinctada margaritifera) are farmed for producing black pearls within remote atolls of French Polynesia. Previous mass-mortality events have resulted in the collapse of oysters and other species; however, the causes and conditions that favour recovery are unclear. We investigated the potential for oyster population recovery 5 years after a mortality event at Takaroa Atoll (Tuamotu Archipelago). Temperature, food availability (total chlorophyll-a), growth and reproduction were monitored. Growth was also simulated using a Dynamic Energy Budget model. Despite favourable conditions, reduced growth and reproduction signalled an energetic deficit. The model overpredicted growth, and supported the hypotheses that individuals are unable to profit from the phytoplankton available and maintenance costs are high in Takaroa, ultimately explaining their poor physiological condition.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112329DOI Listing
June 2021

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

CNRS, Aix-Marseille University, Centrale Marseille, iSm2, 13013 Marseille, France.

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.
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http://dx.doi.org/10.3390/ijms22063253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005207PMC
March 2021