Organoidmodeller av hepatocellulært karsinom
Organoidmodeller av hepatocellulært karsinom for å teste behandlingseffektivitet, utforske korrelasjoner med tumormikro-miljø og tarm-lever-tumoraks.
A promising tool to elucidate the molecular characteristics of HCC are patient-derived organoids (PDOs), three-dimensional cultures of cells that self-organise according to tissue-specific patterns and can be used to test the susceptibility of a specific tumour to anticancer agents. In this study, PDOs for HCC will be developed that closely resemble the tumour microenvironment in vivo and mimic the crosstalk of the gut-liver axis to establish a correlation with patient prognosis and test the efficacy of available systemic therapies.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
The objectives of the project will be 1) to develop HCC PDOs from tumour and non-tumour patient liver tissue obtained from surgical specimens or liver biopsies; 2) to evaluate genomic and transcriptomic changes resulting from the integration of HCC PDOs with patient-derived gut microbiota and host immune cells, and to assess the correlation with patient prognosis; 3) to exploit HCC PDOs to test the efficacy of systemic therapies (ICI and TKIs) and to understand possible modifying cofactors.
Researchers with laboratory experience have been recruited who will focus on the construction of PDOs and the analysis of immune-inflammatory pathways. State-of-the-art technologies will be used, in particular next-generation sequencing, flow cytometry, high-throughput genomic and transcriptomic analysis, ultrafiltration, drug screening, multiplex immunoassays and enzyme immunoassays. The project aims to study the mechanisms involved in the modulation of therapeutic efficacy in patients with HCC. Therefore, the experimental model could be a valuable support to be integrated into real clinical practice to maximise therapeutic efficacy through a fully customised strategy.
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Francesca Romana Ponziani, PI
- Telefonnummer: 3471227242
- E-post: francescaromana.ponziani@policlinicogemelli.it
Studer Kontakt Backup
- Navn: Elisabetta Creta, SC
- Telefonnummer: 3480778584
- E-post: elisabetta.creta@policlinicogemelli.it
Studiesteder
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Roma, Italia, 00168
- Rekruttering
- Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8
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Ta kontakt med:
- Francesca Romana Ponziani
- Telefonnummer: +393471227242
- E-post: francescaromana.ponziani@policlinicogemelli.it
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Hovedetterforsker:
- Francesca Romana Ponziani
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Capacity to express informed consent;
- Age ≥18 years;
- Suspected radiological diagnosis of HCC or diagnosis of HCC with indications for surgical resection.
Exclusion Criteria:
- Age < 18 years;
- Contraindications to liver biopsy (ascites, platelets<50,000, INR>1.7);
- Contraindications to HCC resection surgery;
- Active viral infection;
- Refusal to sign informed consent to participate in the study.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: HCC organoid models development
The aim of the present project is to develop a HCC organoid model that closely resembles the in vivo immunological microenvironment, including the contribution of the gut-liver axis. These reconstituted HCC models will then allow us to test tumor sensitiv |
Enrolled patients will undergo liver biopsy with sampling of tumor tissue and adjacent nontumor liver parenchyma. Alternatively, patients who are candidates for surgical resection of HCC will be enrolled. The tumor tissue obtained will be used partly for histological confirmation of HCC and then included in kerosene, partly used for organoid construction, and the nontumor tissue will be used solely for organoids. Genomic and transcriptomic changes resulting from the integration of PDO of HCC with the gut microbiota and host immune cells derived from the patient will be evaluated. In addition, PDOs from HCC will be tested for the efficacy of systemic therapies (ICI and TKI) and understand possible modifying co-factors. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Organoid model development
Tidsramme: 2-18 months
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The primary endpoint of this study is to assess the correlation between the genomic and histological characteristics of patient-derived organoids (PDOs) from hepatocellular carcinoma (HCC) surgical biopsies and clinical outcomes, specifically disease-free survival (DFS) and overall survival (OS). |
2-18 months
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Francesca Romana Ponziani, PI, Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 6845
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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