laparoscopic-anatomical-liver-segment-vii-resection-with-liver

Laparoscopic Anatomical Liver Segment VII Resection with Liver Parenchymal Transection Following a Priority Approach

Laparoscopic liver resection procedures have rapidly developed, including surgical techniques ranging from early local resection of the liver margin and ...

The second affiliated hospital of Guangzhou university of Chinese Medicine

The long non-coding RNA FOXD2-AS1 is highly expressed in non-small cell lung cancer and promotes malignant progression. However, the role of FOXD2-AS1 in esophageal squamous cell carcinoma (ESCC) is still unclear.

Upregulation of the long noncoding RNA FOXD2-AS1 predicts poor prognosis in esophageal squamous cell carcinoma.

Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtype-specific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.

A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets.

Loss of terminal differentiation markers and gain of stem cell-like properties are a major hallmark of cancer malignant progression. Identification of novel biomarkers representing tumor developmental progeny and predictive of patients' prognosis would greatly benefit clinical cancer management.

Identification of prognostic claudins signature in hepatocellular carcinoma from a hepatocyte differentiation model.

Tumor lineage plasticity is emerging as a critical mechanism of therapeutic resistance and tumor relapse. Highly plastic tumor cells can undergo phenotypic switching to a drug-tolerant state to avoid drug toxicity. Here, we investigate the transmembrane tight junction protein Claudin6 (CLDN6) as a therapeutic target related to lineage plasticity for hepatocellular carcinoma (HCC).  was highly expressed in embryonic stem cells but markedly decreased in normal tissues. Reactivation of CLDN6 was frequently observed in HCC tumor tissues as well as in premalignant lesions. Functional assays indicated that CLDN6 is not only a tumor-associated antigen but also conferred strong oncogenic effects in HCC. Overexpression of CLDN6 induced phenotypic shift of HCC cells from hepatic lineage to biliary lineage, which was more refractory to sorafenib treatment. The enhanced tumor lineage plasticity and cellular identity change were potentially induced by the CLDN6/TJP2 (tight junction protein 2)/YAP1 (Yes-associated protein 1) interacting axis and further activation of the Hippo signaling pathway. A de novo anti-CLDN6 monoclonal antibody conjugated with cytotoxic agent (Mertansine) DM1 (CLDN6-DM1) was developed. Preclinical data on both HCC cell lines and primary tumors showed the potent antitumor efficiency of CLDN6-DM1 as a single agent or in combination with sorafenib in HCC treatment.

Targeting tumor lineage plasticity in hepatocellular carcinoma using an anti-CLDN6 antibody-drug conjugate.

Laparoscopic hepatectomy is a proven safe and technically feasible approach for liver tumor resection, but laparoscopic anatomical SVIII resection (LASVIIIR) remains rarely reported due to poor accessibility, difficult exposure, and the deep-lying Glissonean pedicle. This study examined the safety, feasibility, and perioperative outcomes of LASVIIIR  a middle hepatic fissure approach at our institution.

Article	Year
Upregulation of the long noncoding RNA FOXD2-AS1 predicts poor prognosis in esophageal squamous cell carcinoma. Cancer biomarkers : section A of Disease markers\| PubMed ID: 29286915	2018
A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 32123069	2020
Identification of prognostic claudins signature in hepatocellular carcinoma from a hepatocyte differentiation model. Hepatology international\| PubMed ID: 32304089	2020
Targeting tumor lineage plasticity in hepatocellular carcinoma using an anti-CLDN6 antibody-drug conjugate. Science translational medicine\| PubMed ID: 33536280	2021
Laparoscopic anatomical SVIII resection middle hepatic fissure approach: Caudal or cranio side. World journal of gastrointestinal surgery\| PubMed ID: 39734445	2024

Jiaqiang Mo

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