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1.
Hepatobiliary Pancreat Dis Int ; 21(2): 106-112, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34583911

ABSTRACT

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/surgery , Humans , Immunosuppressive Agents/adverse effects , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Liver Transplantation/methods , Multicenter Studies as Topic , Neoplasm Recurrence, Local/drug therapy , Prospective Studies , Quality of Life , Sirolimus/adverse effects , Treatment Outcome
2.
Biosci Biotechnol Biochem ; 83(6): 1035-1044, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30973065

ABSTRACT

Pituitary adenomas (PA) are commonly occurring benign neoplasms. Identification of molecular pathway resulting in pituitary tumorigenesis remains challenges in endocrine oncology. The present study was conducted with aim of investigating the role of microRNA-543 (miR-543) in PA development. Up-regulated miR-543 and downregulated Smad7 were observed in PA tissues. Afterwards, the specific mechanism of miR-543 and Smad7 in PA were determined with the use of ectopic expression, depletion and reporter assay experiments. Smad7 was confirmed as a target gene of miR-543. HP75 cells treated with overexpressed miR-543 exhibited increased cell proliferation, migration and invasion, while decreased cell apoptosis as well as expression of Cleaved caspase-3 and Cleaved caspase-8 were observed. Suppression of miR-543 contributed to an opposite trend to the above findings. Based on the findings, the inhibition of miR-543 was found to play a tumor suppressive role in PA through the down-regulation of Wnt/ß-catenin pathway by negatively regulating Smad7.


Subject(s)
Adenoma/metabolism , Adenoma/pathology , Apoptosis/genetics , MicroRNAs/physiology , Neoplasm Invasiveness/genetics , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Smad7 Protein/metabolism , Wnt Signaling Pathway , beta Catenin/metabolism , Adult , Caspase 3/metabolism , Caspase 8/metabolism , Cell Line , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation , Female , Humans , Male , Middle Aged , Up-Regulation
3.
J BUON ; 23(6): 1717-1724, 2018.
Article in English | MEDLINE | ID: mdl-30610799

ABSTRACT

PURPOSE: UNC119 was reported to be significantly up-regulated in hepatic cancer cells. However, the clinical significance of target UNC119 to reduce UNC119 expression and mechanisms in hepatocellular carcinoma (HCC) are not well understood. Our purpose was to study how UNC119 is expressed in HCC and its connection with HCC progression. METHODS: UNC119 expression was assessed with quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical analyses in HCC cell lines and in tissues. The biological function of UNC119 for proliferation, growth and cell cycle of tumor cells were also analyzed both in vitro and in vivo. RESULTS: UNC119 expression was up-regulated both in HCC cell lines as well as in tissues through comparison with normal liver cells and tissues. Higher concentration level of UNC119 not only promoted proliferation, but also enhanced migration and invasion of HCC cells. UNC119 promoted the progression of cell cycle and significantly promoted HCC cells growth through Wnt/ß-catenin signal pathway and enhanced tumor migration and invasion via TGF-ß/epithelial-mesenchymal transition (EMT) pathway. Antibody for UNC119 (Anti-UNC119) efficiently inhibited HCC cells proliferation, migration and invasion by blocking Wnt/ß-catenin and TGF-ß/EMT signal pathway, respectively. Anti-UNC119 was not only beneficial for tumor remission, but also contributed to long-term survival of HCC-bearing mice. CONCLUSION: UNC119 is significantly up-regulated and promoted cell growth and migration in hepatic cancer cells and tissues via Wnt/ß-catenin signal pathway and TGF-ß/EMT signal pathway, respectively. Anti-UNC119 treatment inhibited cell proliferation, growth, migration and invasion through inhibition of Wnt/ß-catenin and GF-ß/EMT signal pathway, respectively.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carcinoma, Hepatocellular/pathology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Transforming Growth Factor beta1/metabolism , Wnt Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Apoptosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Movement , Cell Proliferation , Female , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Transforming Growth Factor beta1/genetics , Tumor Cells, Cultured , Wnt Proteins/genetics , Xenograft Model Antitumor Assays , beta Catenin
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