Development of a Neuronal Microscope

Development of a Neuronal Microscope for Cell Characterization and Manipulation (Neuronal micRoscopy for cEll Behavioral Examination and mAnipuLation)

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Carcinoma
• Intervention / Treatment: Genetic: genetic model

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Milan, Milano, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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.

Exclusion Criteria:

• positivity for chronic viral hepatitis (HCV-RNA and HBsAg).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neuronal micRoscopy for cEll behaVioural Examination and mAnipuLation; validate the ability of a neuronal microscope to decipher the biomechanism at the origin of liver cancer, especially addressing the problem of biological heterogeneity	Genetic: genetic model; Create a complete molecular-level description of the heterogeneous population of cells that are capable of giving rise to tumor transformation in the liver.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Isolation of epithelial cells	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.	January 2021 - January 2025
Omics studies and functional morphological studies	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 engineering	January 2021 - January 2025

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): January 1, 2025

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Investigative Techniques; Models, Theoretical; Models, Biological; Models, Genetic
• Other Study ID Numbers: REVEAL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No