Organoids, Intrahepatic Cholangiocarcinoma
Conditions
Keywords
Organoid
Brief summary
The clinical incidence of intrahepatic cholangiocarcinoma (ICC) is high and insidious, and the prognosis of advanced patients is poor. The clinical manifestations of traditional chemotherapy GC and emerging targeted therapy are different in most patients, and there is still no effective scheme to evaluate the differences in individual patient reactivity. Patient-derived tumor organoids (PDO) are 3D-cultured tissues based on tumor cell dryness that reproduce a variety of biological characteristics of parental tumors in vitro and have similar drug responsiveness to tumors in vivo. This project plans to use clinical cases and optimized organoid culture system to first construct relevant organoids from unresectable ICC patient puncture samples. Secondly, based on the organoid model of intrahepatic cholangiocarcinoma, the clinical efficacy of GC regimen was predicted, and in vitro and in vivo drug screening was conducted to explore the guidance of patient-derived tumor organoids for clinical treatment. Then, multi-omics data of organoids and in vitro and in vivo drug efficacy evaluation model were used to explore the drug resistance genes of intrahepatic cholangiocarcinoma, providing the basis for personalized drug screening and efficacy evaluation of intrahepatic cholangiocarcinoma.
Interventions
DEVICEgemcitabine + cisplatin
Gemcitabine intravenous drip, day 1, 8； Cisplatin intravenous drip, day 1； 3 weeks is a cycle, and 6 cycles are used continuously.
Sponsors
Chengjun Sui,MD
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
\- Histologically confirmed intrahepatic cholangiocarcinoma They are between 18 and 80 years old Written informed and signed consent form Biopsy sample of the intrahepatic bile duct
Exclusion criteria
\- Under 18, over 80 Informed consent cannot be given Biopsy samples were not available
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Consistency of organoids and clinical patient responses to drugs | 3 years | A total of 20 unresectable ICC patients were selected and biopsies were performed before treatment to construct organoid models. All patients were treated with GC chemotherapy. Drug responses of organoids and clinical patients were compared to determine the feasibility of in vitro organoid culture as a drug screening platform. The samples of 3 patients who were sensitive to GC and 3 patients who were resistant to GC were sequenced to search for drug-resistant genes, and the differential drug-resistant genes were studied in vitro. |
| Construction of drug resistance prediction model | 3 years | A total of 20 patients with advanced unresectable ICC were selected to verify whether they participated in drug resistance by combining 1-2 drug resistance genes previously screened and the currently recognized platinum-based drug resistance genes. The results were compared with those of organoid models to build an organoid-based drug resistance prediction model. |
Contacts
Primary Contactzhitao dong, dr.
Backup Contactkunpeng fang, dr.
Outcome results
None listed