Development of a Neuronal Microscope
- Conditions
- Hepatic Carcinoma
- Interventions
- Genetic: genetic model
- Registration Number
- NCT06311396
- Brief Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. The prognosis of HCC remains poor, with a 5-year survival rate of 18%. Risk factors for HCC include viral infection, autoimmune hepatitis, chronic alcohol use or metabolic fatty liver disease, obesity, and diabetes mellitus.
- Detailed Description
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. The prognosis of HCC remains poor, with a 5-year survival rate of 18%. Risk factors for HCC include viral infection, autoimmune hepatitis, chronic alcohol use or metabolic fatty liver disease, obesity, and diabetes mellitus. Furthermore, alterations and chronic inflammation of the microenvironment can facilitate the transformation of normal liver stem cells into precancerous tumor stem cells. All these underlying pathogenic stimuli can induce a spectrum of genetic and epigenetic modifications, which are involved in the cell cycle, cell growth and regulation of adhesion. Therefore, heterogeneity and tumor priming potential arise from a combination of both endogenous and exogenous factors. However, current in vitro models, based on conventional hepatoma and hepatocarcinoma cell lines, fail to recapitulate key characteristics of tumor tissue such as three-dimensional tissue architecture, cellular heterogeneity, and cell-cell interactions. Organoids, which are 3D cellular structures generated from induced pluripotent stem cells and adult tissue-resident stem cells, have recently been exploited to overcome the limitations of 2D cell culture systems, emerging as powerful tools for studying human diseases. Therefore, organoid structures stably preserve the genetic information of autologous tissue by mimicking the pathological state of the tissue itself.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 30
Patients aged >18 years:
- undergoing surgical cholecystectomy, liver resection for hepatocellular carcinoma (both intra-tumoral and extra-tumoral tissues) or whole liver explants;
- who have given consent to participate in the study.
• positivity for chronic viral hepatitis (HCV-RNA and HBsAg).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neuronal micRoscopy for cEll behaVioural Examination and mAnipuLation genetic model validate the ability of a neuronal microscope to decipher the biomechanism at the origin of liver cancer, especially addressing the problem of biological heterogeneity
- Primary Outcome Measures
Name Time Method Omics studies and functional morphological studies January 2021 - January 2025 * Knowledge of the behavioral and morphological differences between physiological and tumor hepatocytes;
* Knowledge of the molecular mechanisms underlying cellular level observations exploiting "omics" scale assessments and CRISPR-Cas9 genetic engineeringIsolation of epithelial cells January 2021 - January 2025 Isolation of epithelial cells to ultimately generate models of major hepatocellular carcinoma cell populations in three-dimensional culture environment, called liver organoids, and molecular characterization of the generated models.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica
🇮🇹Milan, Milano, Italy