fluorescent-laparoscopic-central-hepatectomy-for-liver-cancer-using

Fluorescent Laparoscopic Central Hepatectomy for Liver Cancer Using Indocyanine Green Negative Staining

Laparoscopic hepatectomy is an important treatment method for liver cancer. In the past, the resection boundary was usually determined by intraoperative ...

Sun Yat-sen University

The deregulation of microRNAs (miRNAs) plays an important role in human hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in hepatocellular carcinoma (HCC) cells. First, we examined the different miRNA expression profiles in HCC cells and HCC cell-derived exosomes. Next, coculture experiments indicated that HCC cell-derived exosomes promoted the cell growth, migration, and invasion of HCC cells and had the ability to shuttle miRNAs to recipient cells. Further, our data showed that Vps4A, a key regulator of exosome biogenesis, was frequently down-regulated in HCC tissues. The reduction of Vps4A in HCC tissues was associated with tumor progression and metastasis. In vitro studies revealed that Vps4A repressed the growth, colony formation, migration, and invasion of HCC cells. We further investigated the role and involvement of Vps4A in suppressing the bioactivity of exosomes and characterized its ability to weaken the cell response to exosomes. By small RNA sequencing, we demonstrated that Vps4A facilitated the secretion of oncogenic miRNAs in exosomes as well as accumulation and uptake of tumor suppressor miRNAs in cells. A subset of Vps4A-associated miRNAs was identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the phosphatidylinositol-3-kinase/Akt signaling pathway was the most likely candidate pathway for modulation by these miRNAs. Indeed, we proved that the phosphatidylinositol-3-kinase/Akt pathway was inactivated by Vps4A overexpression.

Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells.

Follicular dendritic cell sarcoma (FDCS) is a rare tumor associated with paraneoplastic pemphigus. It is Blame drenchs auxiliary cell tumor which is derived from the peripheral lymphoid tissues. Throughout the world, several patients of paraneoplastic pemphigus associated follicular dendritic cell sarcoma were reported in the literature, but mostly originated from the neck lymph nodes, and extranodal origin of follicular dendritic sarcoma was rarely reported. Also, so far we have found that the malignant degree of all patients diagnosed with malignant tumors have been reported were low and after combined treatment of surgery, radiotherapy and chemotherapy, most of the prognosis was good. However, here we present a patient of paraneoplastic pemphigus associated with follicular dendritic cell sarcoma origined from outside of the lymph nodes and had high tumor malignant degree for its unclear cell boundaries, obvious atypia and mitoses and the patient's state became progressively deteriorate after operation.

Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma: report of a case and review of literature.

Besides surgical treatment, systematic chemotherapy plays a crucial role in HCC treatment, especially for patients with advanced HCC. However, none of the single-drug-treatment strategies have shown significant survival benefit due to a high incidence rate of chemoresistance. This study was designed to observe the effect of small interfering of RNA (SiRNA) targeting multidrug resistance-related protein 1-4 (MRP1, MRP2, MRP3, and MRP4) in modulating drug resistance of HepG2/ADM and SMMC7721/ADM cells.

Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy.

Duodenum-preserving total pancreatic head resection (DPPHRt) is an accepted alternative surgical procedure for benign or low-grade malignant tumors of the pancreatic head by preserving the duodenum with its intact blood supply from the pancreatic duodenal arterial arcade. This study describes our experience in laparoscopic DPPHRt (LDPPHRt). To our knowledge, this is the first description of this novel minimally invasive operation.

Laparoscopic duodenum-preserving total pancreatic head resection: a novel surgical approach for benign or low-grade malignant tumors.

We previously reported that Vps4A acted as a tumor suppressor by influencing the microRNA profiles of exosomes and their parental cells in hepatocellular carcinoma (HCC). However, the underlying mechanism and if Vps4A contributes to sorting proteins into exosomes are not well known. Here, we performed mass spectrometry analysis of the immunoprecipitated Vps4A complex and confirmed that Vps4A was associated with β-catenin and CHMP4B. Through this interaction, Vps4A promoted the plasma membrane (PM) localization and exosome release of β-catenin. Silencing Vps4A or CHMP4B decreased the PM localization and exosome sorting of β-catenin. Vps4A overexpression decreased β-catenin signaling pathway and inhibited epithelial-mesenchymal transition (EMT) and motility of HCC cells. And, silencing Vps4A or CHMP4B promoted EMT in HCC. Furthermore, the expression of Vps4A was significantly related to that of several EMT markers in HCC tissues and the level of exosomal β-catenin in patients with metastatic HCC was significantly lower compared to that of control patients. In conclusion, through the interaction with CHMP4B and β-catenin, Vps4A regulates the PM localization and exosome sorting of β-catenin, consequently decreases β-catenin signaling, and thereby inhibits EMT and metastasis in HCC.

Vps4A mediates the localization and exosome release of β-catenin to inhibit epithelial-mesenchymal transition in hepatocellular carcinoma.

CircRNAs involved in the development of many diseases have been recently identified. However, the possible role of circRNAs in human hepatocellular carcinoma (HCC) remains to be investigated.

The role of circular RNA hsa_circ_0085616 in proliferation and migration of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown.

Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce rapid hypertrophy of the liver remnant. However, with a background of liver cirrhosis or other chronic liver diseases, patients with a huge hepatocellular carcinoma (HCC) may sometimes face insufficiency of hepatocellular regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Herein, we report a 56-year-old male with a vast HCC (13.3 × 8.5 × 13 cm) whose ratio of the future liver remnant (FLR)/standard liver volume (SLV) was 28.7% when the disease was first diagnosed. Inadequate hypertrophy of FLR was shown in postoperative volumetric assessment a month after stage I ALPPS. After multidisciplinary team discussion (MDT), the patient was decided to follow three courses of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). The last HAIC was performed together with transhepatic arterial embolization (TAE). Finally, ratio of the FLR/SLV increased from 28.7% to 40% during three-month intervals, meeting the requirements of the surgery. Stage II ALPPS, right trisectionectomy, was then successfully performed. There was no recurrence at half years of follow-up. In our case, HAIC seems to be more potent than transcatheter arterial chemoembolization (TACE) in maintaining the hyperplasia of the liver remnant, reducing tumor load, and preventing tumor progression in patients with a large HCC during ALPPS procedure. HAIC, following the first step of ALPPS, a pioneering treatment modality aiming for inadequate hypertrophy of FLR induced by ALPPS, could be an alternative procedure for patients with a vast HCC in clinical practice.

Case Report: Hepatic Artery Infusion Chemotherapy After Stage I ALPPS in a Patient With Huge HCC.

p62 is a multi-domain protein and participates in a variety of cellular biological activities. p62 is also related to tumor malignancy. However, the underlying molecular mechanism of p62 regulating the progression of hepatocellular carcinoma (HCC) remains unclear.

Article	Year
Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells. Hepatology (Baltimore, Md.)\| PubMed ID: 25503676	2015
Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma: report of a case and review of literature. International journal of clinical and experimental pathology\| PubMed ID: 26722384	2015
Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy. American journal of translational research\| PubMed ID: 27398162	2016
Laparoscopic duodenum-preserving total pancreatic head resection: a novel surgical approach for benign or low-grade malignant tumors. Surgical endoscopy\| PubMed ID: 30456509	2019
Vps4A mediates the localization and exosome release of β-catenin to inhibit epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer letters\| PubMed ID: 31059752	2019
The role of circular RNA hsa_circ_0085616 in proliferation and migration of hepatocellular carcinoma cells. Cancer management and research\| PubMed ID: 31496798	2019
Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma. Cell communication and signaling : CCS\| PubMed ID: 32183816	2020
Case Report: Hepatic Artery Infusion Chemotherapy After Stage I ALPPS in a Patient With Huge HCC. Frontiers in surgery\| PubMed ID: 34901139	2021
p62 Promotes Malignancy of Hepatocellular Carcinoma by Regulating the Secretion of Exosomes and the Localization of β-Catenin. Frontiers in bioscience (Landmark edition)\| PubMed ID: 35345321	2022

Jinxing Wei

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