Project description:Experiment was to determine the effects of G9a inhibition using chemical inhibitor UNC0638 on murine lung adenocarcinoma cell lines
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
Project description:We used whole genome microarray expression profiling as a discovery platform to identify genes through 7 pairs lung adenocarcinoma tissues and normal tissues
Project description:FVB, Balb/c, and C57BL/6 mice received the tobacco carcinogens urethane (Sigma Aldrich, U2500) intraperitoneally (1g/Kg in 100 μl phosphate-buffered saline) or diethylnitrosamine (200 mg/kg) (Sigma Aldrich, N0756). Carcinogen induced lung adenocarcinoma murine cell lines generation| Ten months post first carcinogen (urethane, DEN) exposure mice were sacrificed, lung tumours were dissected from surrounding healthy lung parenchyma under sterile conditions, were halved, one half was processed for histology and the other half was chopped into 1 mm pieces and seeded to cell culture dishes. Cells were cultured under standard conditions outlined below. When adenocarcinoma was diagnosed for a given tumour, its corresponding culture was passaged in vitro over a period of 18 months and 60 passages, whichever occurred first. After gene expression and mutational signature extraction, the signature were compared with human lung adenocarcinoma RNAseq results.
Project description:The World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC), adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns Pure invasive adenocarcinomas are often devoid of bronchioloalveolar morphology. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in non-mucinous BAC is significantly lower than that of pure invasive tumors and in tumors with greater than 0.6 cm of fibrosis or linear invasion (J Thorac Oncol 6:244-285) To identify human tumor cell signatures associated with lung adenocarcinoma subtype and invasion, we performed microarray gene expression profiling of microdissected tumor cells noninvasive AC and AC-Mixed invasive tumors. 17 cases of noninvasive AC tumors and 23 cases of AC-mixed subtype invasive lung adenocarcinomas resected from 2002 to 2006 were examined (Columbia Lung Adenocarcinoma dataset)
Project description:To identify proteomic of lung adenocarcinoma, we collected five pairs of lung adenocarcinoma and normal lung tissues from the clinic for analysis