Dataset Information

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

ABSTRACT: Compared to various traditional 2D approaches, the scaffold-based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal-like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells and human umbilical vein endothelial cells cocultured in poly(lactic-co-glycolic acid)-based porous microspheres (PLGA PMs) is reported. In contrast to the conventional 2D culture, the cells within the PLGA PMs exhibit significantly higher half-maximal inhibitory concentration values against anticancer drugs, including doxorubicin and cisplatin. Furthermore, the feasibility of coculturing other cell types, such as fibroblasts (L929) and HepG2 cells, is investigated. Together, the findings emphasize the significance of engineered 3D hepatic tumor microtissue models using PLGA PM-based multicellular aggregates for drug screening applications.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7610277 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Wang Ying Y Kankala Ranjith Kumar RK Zhang Jianting J Hao Liuzhi L Zhu Kai K Wang Shibin S Zhang Yu Shrike YS Chen Aizheng A

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200921 21

Compared to various traditional 2D approaches, the scaffold-based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal-like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells a ...[more]

PMID: 33173735

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Project description:BACKGROUND: Head and neck cancer (HNC) belongs to a group of heterogeneous disease with distinct patterns of behavior and presentation. TNFRSF10B, a tumor suppressor gene mapped on chromosome 8. Mutation in candidate gene is responsible for the loss of chromosome p arm which is frequently observed in head and neck tumors. TNFRSF10B inhibits tumor formation through apoptosis but deregulation encourages metastasis, migration and invasion of tumor cell tissues. RESULTS: Structural modeling was performed by employing MODELLER (9v10). A suitable template [2ZB9] was retrieved from protein databank with query coverage and sequence identity of 84% and 30% respectively. Predicted Model evaluation form Rampage revealed 93.2% residues in favoured region, 5.7% in allowed region while only 1 residue is in outlier region. ERRAT and ProSA demonstrated 51.85% overall quality with a -1.08 Z-score of predicted model. Molecular Evolutionary Genetics Analysis (MEGA 5) tool was executed to infer an evolutionary history of TNFRSF10B candidate gene. Orthologs and paralogs [TNFRSF10A & TNFRSF10D] protein sequences of TNFRSF10B gene were retrieved for developed ancestral relationship. Topology of tree presenting TNFRSF10A gene considered as outgroup. Human and gorilla shared more than 90% similarities with conserved amino acid sequence. Virtual screening approach was appliedfor identification of novel inhibitors. Library (Mcule) was screened for novel inhibitors and utilized the scrutinized lead compounds for protein ligand docking. Screened lead compounds were further investigated for molecular docking studies. STRING server was employed to explore protein-protein interactions of TNFRSF10B target protein. TNFSF10 protein showed highest 0.999 confidence score and selected protein-protein docking by utilizing GRAMM-X server. In-silico docking results revealed I-58, S-90 and A-62 as most active interacting residues of TNFRSF10B receptor protein with R-130, S-156 and R-130 of TNFSF10B ligand protein. CONCLUSION: Current research may provide a backbone for understanding structural and functional insights of TNFRSF10B protein. The designed novel inhibitors and predicted interactions might serve to inhibit the disease. Effective in-vitro potent ligands are required which will be helpful in future to design a drug to against Head and neck cancer disease. There is an urgent need for affective drug designing of head and neck cancer and computational tools for examining candidate genes more efficiently and accurately are required.

Dataset Information

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Publications

Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening.

Similar Datasets

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