Impact of Sympathetic Autonomic Innervation of The

il y a 2 semaines

Rennes, France Institut Nutrition, Métabolismes et Cancer (INSERM, Univ Rennes, INRAe) Temps plein

**Impact of sympathetic autonomic innervation of the tumor microenvironment on the progression of human hepatocellular carcinoma.**:

- Réf **ABG-122255**
- Sujet de Thèse- 04/04/2024- Contrat doctoral- Institut Nutrition, Métabolismes et Cancer (INSERM, Univ Rennes, INRAe)- Lieu de travail- RENNES - Bretagne - France- Intitulé du sujet- Impact of sympathetic autonomic innervation of the tumor microenvironment on the progression of human hepatocellular carcinoma.- Champs scientifiques- Santé, médecine humaine, vétérinaire
- Biotechnologie
- Mots clés- cancer, microenvironnement, inflammation, fibrose, catécholamines, immunité, pathologie moléculaire, bio-informatique, intelligence artificielle**Description du sujet**:
Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide. It has been classified by the French National Cancer Institute (INCa) as a poor-prognosis cancer, with a 5-year survival rate of less than 33%. The chronic fibroinflammatory liver disease background leads to increased innate immune reactivity and extracellular matrix remodeling.1 This microenvironment sets the stage for the emergence of cancer stem/progenitor cells.

HCCs are generally highly cellular tumors, with a soft consistency on macroscopic examination and little intratumor fibrosis. However, within certain HCCs, fibro-inflammatory foci may be distinguished on microscopic examination. These foci are composed of extracellular matrix, cancer-associated fibroblasts, immune cells and growth factors and have been called _"Fibrous Nests."_2-3 HCCs containing fibrous nests are enriched in cancer stem/progenitor cells, WNT/TGFB signals;2-3 and their proteomic signatures;4-5 indicate that they belong to the most aggressive class of HCCs, known as ECM/STEM.6-7

Intra-tumor fibrosis in HCCs may be linked to an immunosuppressive environment and to a presence of sympathetic nerve endings at the tumor invasion front. In this microenvironment, cancer-associated fibroblasts, neo-formed sympathetic nerve endings and the extracellular matrix could exert mechanical forces activating pro-tumor signals leading to the amplification of cancer stem/progenitor cell populations and tumor invasion.

Our project aims to assess the impact of intra-tumor fibrosis and its sympathetic innervation on HCC progression. The hallmarks of this three-year PhD project include prognostic evaluation of fibrosis and sympathetic innervation in 200 HCC cases (project approved by the INSERM Ethics Committee), analysis of the mechanical forces therein, affected signaling networks, and in vitro modeling of mechanical forces under defined adrenergic environments and extracellular matrix compositions.

**References**:

- JHEP Reports (2023), 6 :100936
- Oncotarget (2016), 7:39026
- Int J Biochem Cell Biol (2016), 81(Pt A):195
- Hepatology (2023), 78: 741
- Hepatology (2023), 78:691
- Hepatology (2017), 66:1502
- World journal of Gastroenterology (2018), 24:4536

**Prise de fonction**:

- 01/10/2024**Nature du financement**:

- Contrat doctoral**Précisions sur le financement**:

- Acquis (2024 - 2027)**Présentation établissement et labo d'accueil**:

- Institut Nutrition, Métabolismes et Cancer (INSERM, Univ Rennes, INRAe)- After constructing a transcriptomic meta-database (GSE237977) and analyzing 1133 HCCs, we revealed a distribution of HCC heterogeneity in 2 dimensions: 1st dimension: proliferation/differentiation ratios, fibrosis, and stem cells; 2nd dimension: preservation of metabolic pathways. Four subclasses, PERIPORTAL, PERIVENOUS, EXTRACELLULAR MATRIX (ECM), and STEM, form a continuum of increasing malignancy,1, 2 with specific metabolic characteristics related to their chemoresistance.3 HCCs are generally highly cellular tumors, with a soft consistency on macroscopic examination and little intratumor fibrosis.4 However, on microscopic examination, in 30% of HCCs, intratumor foci of fibrosis are observed, i.e., extracellular matrix (ECM) deposits, that we termed _"Fibrous Nests,"_5_ _with enrichment in cancer stem/progenitor cells, WNT/TGFB signals and cancer-associated fibroblasts.5-7 The proteomic signature8 of these HCCs suggests that they belong to the most aggressive class of HCCs, known as ECM/STEM and that _Fibrous Nests_ are cancer stem cell niches.1, 9 This fibroinflammatory desmoplastic stroma could promote tumor progression through mechano-transduction and an immunosuppressive microenvironment.10 These encouraging results7, 8 were obtained from 20 HCCs and their matching non-tumor livers, and proteomics data were integrated with The Cancer Genome Atlas (TCGA, n= 370) and our previously described (GSE237977, n= 1133) HCC transcriptomic dataset. To translate these findings to the clinical setting, direct quantification of intratumor fibrosis and validation of key protein markers in a large HCC collection will be necessary.**References**

[1] Hepatology 2017, 66:1502-18.

[2] Hepatology 2017, 66:1377-80.

[3] Cancer research 2019,

  • Upscaling The Impact of Heterogeneity On Subsurface

    il y a 1 mois

    Rennes, France Geosciences Rennes (UMR6118) Temps plein

    **Upscaling the impact of heterogeneity on subsurface heat transport processes: towards the catchment/regional scale modelling**: - Réf - **ABG-111294** - Sujet de Thèse- 20/02/2023- Financement de l'Union européenne- Geosciences Rennes (UMR6118)- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Upscaling the impact of heterogeneity on...

  • Theory of The Complex Luminescence Properties of

    il y a 4 semaines

    Rennes, France Université de Rennes Institut des Sciences Chimiques de Rennes Temps plein

    **Theory of the complex luminescence properties of actinides**: - Réf **ABG-122986** - Sujet de Thèse- 17/04/2024- Contrat doctoral- Université de Rennes / Institut des Sciences Chimiques de Rennes- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Theory of the complex luminescence properties of actinides- Champs scientifiques-...

  • Head of The Biology Department

    il y a 2 semaines

    Rennes, France Bioprojet Biotech Temps plein

    Bioprojet Biotech, pharmaceutical research and development center of the Bioprojet laboratory, is recruiting for its site based in Rennes (35) its: Head of the Biology Department - M/F Within the research center which hosts 45 scientists, the biology department develops new research targets by cloning, evaluates chemically synthesized molecules in vitro on...

  • Phd Position at Ietr

    il y a 20 heures

    Rennes, France INSTITUT NATIONAL DES SCIENCES APPLIQUEES Temps plein

    **PhD Position at IETR - Ecodesign of Embedded Systems applied to Smart Vision**: - Réf **ABG-123956** - Sujet de Thèse- 17/05/2024- Contrat doctoral- INSTITUT NATIONAL DES SCIENCES APPLIQUEES- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- PhD Position at IETR - Ecodesign of Embedded Systems applied to Smart Vision- Champs...

  • Phd Position at Ietr

    il y a 20 heures

    Rennes, France INSA RENNES Temps plein

    **About us**: INSA Rennes, a founding member of the INSA Group, is the largest public engineering school in Brittany. It welcomes 2,200 students and apprentices and graduates more than 340 engineers, 60 masters and 40 PhDs per year. Composed of 10 teaching departments, including 7 specialties and an apprenticeship program, and supervised by 6 research...

  • Chair “chaining-interoperability of Digital

    il y a 1 mois

    Rennes, France Springer Nature Temps plein

    **Chair “Chaining-Interoperability of Digital Environmental & Health Data” leading to a prof. position**: - Employer- French National Institute for Health Research (INSERM)- Location- Rennes (Arrondissement), Ille-et-Vilaine (FR)- Salary- According to experience- Closing date- 31 Mar 2024- Discipline Computing, Environmental Science Job Type ...

  • Researcher in the field of Power Electronics – Magnetic components

    il y a 1 mois

    Rennes, France Mitsubishi Electric R&D Centre Europe - France Temps plein

    Context and description:MITSUBISHI ELECTRIC is one of the leading manufacturers of power electronics related products from components such as semiconductor power devices to systems such as HVDC systems. As MITSUBISHI ELECTRIC Group’s subsidiary, MITSUBISHI ELECTRIC R&D CENTRE EUROPE includes a research division specialised in Power Electronics, in...

  • Researcher in the field of Power Electronics – Magnetic components

    il y a 1 semaine

    Rennes, France Mitsubishi Electric R&D Centre Europe - France Temps plein

    Context and description:MITSUBISHI ELECTRIC is one of the leading manufacturers of power electronics related products from components such as semiconductor power devices to systems such as HVDC systems. As MITSUBISHI ELECTRIC Group’s subsidiary, MITSUBISHI ELECTRIC R&D CENTRE EUROPE includes a research division specialised in Power Electronics, in...

  • Researcher in the field of Power Electronics – Magnetic components

    il y a 1 semaine

    Rennes, Ille-et-Vilaine, France Mitsubishi Electric R&D Centre Europe - France Temps plein

    Context and description:MITSUBISHI ELECTRIC is one of the leading manufacturers of power electronics related products from components such as semiconductor power devices to systems such as HVDC systems. As MITSUBISHI ELECTRIC Group’s subsidiary, MITSUBISHI ELECTRIC R&D CENTRE EUROPE includes a research division specialised in Power Electronics, in...

  • Digital Marketing Manager

    il y a 4 jours

    Rennes, France Rennes School of Business Temps plein

    **Rennes School of Business** est une école internationale de management située à Rennes et à Paris. Notre mission est de préparer, par l’enseignement et la recherche, des leaders responsables et innovants à agir efficacement dans un environnement globalisé. Rennes SB se distingue par un corps professoral unique avec près de 90% de professeurs...

  • Development of Fibre Optic Sensors for Distributed

    il y a 4 semaines

    Rennes, France Geosciences Rennes (UMR6118) Temps plein

    **Development of fibre optic sensors for distributed measurement of underground flows with high spatial resolution**: - Réf **ABG-121486** - Sujet de Thèse- 20/03/2024- Contrat doctoral- Geosciences Rennes (UMR6118)- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Development of fibre optic sensors for distributed measurement of...

  • Security Evaluation of Ai-based Hardware

    il y a 1 mois

    Rennes, France Université de Rennes - IETR Temps plein

    **Security Evaluation of AI-Based Hardware Accelerator Units**: - Réf **ABG-120503** - Sujet de Thèse- 20/02/2024- Sans financement dédié- Université de Rennes - IETR- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Security Evaluation of AI-Based Hardware Accelerator Units- Champs scientifiques- Electronique - Numérique - Science de...

  • Doctorant (F/H) Shape Analysis of

    il y a 1 mois

    Rennes, France Inria Temps plein

    **Type de contrat **:CDD **Niveau de diplôme exigé **:Bac + 5 ou équivalent **Fonction **:Doctorant **A propos du centre ou de la direction fonctionnelle**: Le centre Inria de l'Université de Rennes est un des neuf centres d’Inria et compte plus d'une trentaine d’équipes de recherche. Le centre Inria est un acteur majeur et reconnu dans le...

  • Phd Positions in Rennes

    il y a 4 semaines

    Rennes, France Institute of Genetics and Development of Rennes (IGDR) Temps plein

    The IGDr (Institute of Genetics & Development of Rennes) is seeking 4 to 8 motivated PhD students, starting October, 2024. PhD students will conduct their research within one of the 15 teams of the IGDR. Cutting-edge training will be offered on topics encompassing the two main research axes of the IGDR: “Genetics, Genomics and Cancer” and “Cell...

  • Implementation in Realistic Ocean Numerical Code of

    il y a 1 mois

    Rennes, France Inria Temps plein

    **Type de contrat **:CDD **Niveau de diplôme exigé **:Thèse ou équivalent **Fonction **:Ingénieur scientifique contractuel **A propos du centre ou de la direction fonctionnelle**: Le centre Inria de l'Université de Rennes est l'un des huit centres d’Inria et compte plus d'une trentaine d’équipes de recherche. Le centre Inria est un acteur...

  • PhD Position F/M Multimodal Segmentation of Chronic Stroke Lesions

    il y a 1 mois

    Rennes, France INRIA Temps plein

    Contexte et atouts du poste Co-director : Elise Bannier, IR UR, Empenn Co-director : Elisa Fromont, PR UR, Lacodam Co-supervisor : Francesca Galassi, MCF UR, Empenn Co-supervisor : Stéphanie Leplaideur, Medical Doctor, Centre de KERPAPE The selected PhD candidate will have the opportunity to join the research lab Empenn at Inria-Irisa, located...

  • PhD Position F/M Reliability and Security of Large Foundation Models

    il y a 1 mois

    Rennes, France INRIA Temps plein

    PhD Position F/M Reliability and Security of Large Foundation Models Le descriptif de l’offre ci-dessous est en Anglais Type de contrat : CDD Niveau de diplôme exigé : Bac + 5 ou équivalent Fonction : Doctorant A propos du centre ou de la direction fonctionnelle The Inria Rennes - Bretagne Atlantique Centre is one of...

  • Doctorant F/H Shape analysis of microstructure-augmented whiter matter fascicles

    il y a 1 mois

    Rennes, France INRIA Temps plein

    Contexte et atouts du poste Magnetic resonance imaging (MRI) and in particular diffusion MRI (dMRI) provide detailed information about the macroscopic organisation of brain white matter (WM) fiber bundles (see Figure), with a method called fiber tractography. Complementary to the geometry of fibers, dMRI is also sensitive to the microscopic tissue...

  • Development of a Hybrid Machine Learning Model for

    il y a 1 jour

    Rennes, France LTSI - UMR INSERM 1099 Temps plein

    **Development of a hybrid machine learning model for predicting response to cardiac resynchronization therapy**: - Réf **ABG-123925** - Sujet de Thèse- 16/05/2024- Financement public/privé- LTSI - UMR INSERM 1099- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Development of a hybrid machine learning model for predicting response to...

  • Model-based DevOps: From Theory to Practice

    il y a 1 mois

    Rennes, France IRISA Temps plein

    **Model-Based DevOps: From Theory to Practice**: - Réf - **ABG-112242** - Sujet de Thèse- 20/03/2023- Contrat doctoral- IRISA- Lieu de travail- Rennes - Bretagne - France- Intitulé du sujet- Model-Based DevOps: From Theory to Practice- Champs scientifiques- Informatique - Mots clés- DevOps, Digital Twins, Self Adaptive Systems, Model Driven Engineering,...