肝細胞癌のオルガノイドモデル
治療の有効性を検査するための肝細胞癌のオルガノイドモデル、腫瘍微小環境および腸肝臓の軸軸との相関を調査します。
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Francesca Romana Ponziani, PI
- 電話番号：3471227242
- メール：francescaromana.ponziani@policlinicogemelli.it
研究連絡先のバックアップ
- 名前：Elisabetta Creta, SC
- 電話番号：3480778584
- メール：elisabetta.creta@policlinicogemelli.it
研究場所
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Roma、イタリア、00168
- 募集
- Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8
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コンタクト：
- Francesca Romana Ponziani
- 電話番号：+393471227242
- メール：francescaromana.ponziani@policlinicogemelli.it
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主任研究者：
- Francesca Romana Ponziani
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Organoid model development
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Francesca Romana Ponziani, PI、Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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