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Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.
Ding, Dong-Yang; Gan, Xiao-Jie; Zhang, Jia-Ning; Hou, Guo-Jun; Tao, Qi-Fei; Sun, Da-Peng; Li, Wen; Yang, Yuan; Ding, Wen-Bin; Yu, Jian; Liu, Lei; Yang, Fu; Zhou, Wei-Ping; Yuan, Sheng-Xian.
  • Ding DY; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Gan XJ; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Zhang JN; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Hou GJ; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Tao QF; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Sun DP; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Li W; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Yang Y; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Ding WB; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Yu J; Department of General Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China.
  • Liu L; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China. Dr_ray@foxmail.com.
  • Yang F; The Department of Medical Genetics, Naval Medical University, 200438, Shanghai, China. yangfusq1997@smmu.edu.cn.
  • Zhou WP; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China. ehphwp@126.com.
  • Yuan SX; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 200438, Shanghai, China. yuanshengx@126.com.
Br J Cancer ; 128(5): 907-917, 2023 03.
Article en En | MEDLINE | ID: mdl-36526676
ABSTRACT

BACKGROUND:

At present, the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) is gemcitabine combined with cisplatin, but a considerable portion of ICC patients exhibit resistance to gemcitabine. Therefore, finding sensitisers for gemcitabine chemotherapy in ICC patients and predicting molecular markers for chemotherapy efficacy have become urgent needs.

METHODS:

In this study, PDX models were established to conduct gemcitabine susceptibility tests. The selected PDX tissues of the chemotherapy-sensitive group and drug-resistant group were subjected to transcriptome sequencing and protein chip technology to identify the key genes. Sixty-one ICC patients treated with gemcitabine chemotherapy were recruited for clinical follow-up validation.

RESULTS:

We found that thrombospondin-1 (TSP1) can predict gemcitabine chemosensitivity in ICC patients. The expression level of TSP1 could reflect the sensitivity of ICC patients to gemcitabine chemotherapy. Functional experiments further confirmed that TSP1 can increase the efficacy of gemcitabine chemotherapy for ICC. A mechanism study showed that TSP1 may affect the intake of oleic acid by binding to the CD36 receptor.

CONCLUSIONS:

In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Colangiocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Colangiocarcinoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article