Development of a Neuronal Microscope

Hepatic Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06311396
• Other study ID #: REVEAL
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: January 1, 2025

Study information

• Verified date: March 2024
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Luca Vittorio Carlo Valenti
• Phone: 02 5503 6595
• Email: luca.valenti[@]policlinico.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatic Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica	Milan	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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