Project description:Using RNA-seq analysis, we have described in ovo liver cancer models providing the information that could help in preclinical research of new therapies for liver cancer.
Project description:Polydopamine (PDA) is a polymer obtained from the self-polymerization of dopamine monomers; during the synthesis process, spherical nanoparticles are formed (PDA NPs), presenting several interesting properties such as high drug encapsulation capacity, easy and versatile surface modification, ability to convert near-infrared radiation (NIR) into heat, and strong antioxidant properties. In this work, PDA NPs have been proposed as an anti-cancer tool through the combination of NIR-mediated hyperthermia loading with a chemotherapeutic agent, sorafenib (SRF), specifically effective on liver cancer. Cell membranes isolated from hepatocarcinoma cancer cells (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), in order to achieve homotypic targeting. The selective targeting capacity, photothermal, and chemotherapeutic activity of CM-SRF-PDA NPs have been evaluated on cell cultures in static and dynamic conditions, besides on 3D culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex-ovo on a HepG2 spheroids-grafted chorioallantoic membrane model of quail embryos. This comprehensive investigation, supported by proteomic analysis, strongly suggest the developed nanoplatform for further pre-clinical investigations in the treatment of liver cancer.
Project description:Hippo pathway is evolutionarily well conserved. All core components of the pathway identified to date have one or more mammalian orthologs, including MST1/2 (Hippo), SAV1 (Salvador, also known as WW45), LATS1/2 (Warts), MOB1 (Mats), YAP1 and its paralog WWTR1 (also known as TAZ) (Yorkie), and TEAD1/2/3/4 (Scalloped). Ectopic over-expression of YAP1 in mouse liver led to develop hepatocellular carcinoma (HCC). HCC is the third most common cause of cancer-related death in the world, and accounts for an estimated 600,000 deaths annually. Lack of molecular classification and clinical heterogeneity of this malignant disease hampered the development of standardized treatment. To investigate roles of Hippo pathway in liver carcinogenesis, we generated liver-specific Mst1/2 -/- and Sav1 -/- mouse models and collected gene expression data from them. Our study provided new understanding on molecular characteristics of HCC. Sav1 and Mst1/2 Knockout models
Project description:Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.
Project description:A large panel of 81 liver cancer cell models, designated as LIver cancer MOdel REpository (LIMORE) was constructed. These cell lines include 31 public cell lines and 50 new cell models establishend from Chinese liver cancer patients. Whole genome sequencing (WGS), exome sequencing (WES) and RNA sequencing (RNAseq) were performed to obtain the genetic information for these cell lines. These cell lines and associated data provide new models and also a rich resource for liver cancer.
Project description:The therapeutic regimens of adjuvant and neoadjuvant chemotherapy for colorectal cancer (CRC) remain largely relied on clinical experience, and thus preclinical models are needed to guide individualized medicine. The investigators are going to establish 3D bioprinted CRC models and organoids from surgically resected tumor tissues of CRC patients with or without liver metastases. In vitro 3D models and organoids will be treated with the same chemotherapy drugs with the corresponding patients from whom the models are derived. The sensitivity of chemotherapy drugs will be tested in these two types of in vitro models, and the actual response to chemotherapy in patients will be evaluated. The predictive ability of 3D models for chemotherapy sensitivity in CRC patients will be compared with that of the organoids. This observational study will validate the potential value of 3D bioprinted tumor models in predicting the response to chemotherapy in CRC.