Project description:This is a comparative microarray analysis of 36-65 hybridomas switching at normal low frequencies in vitro vs. selected variants spontaneously switching at 100 fold higher frequencies in vitro. This analysis reveals differential gene expression of 2091 unique probe sets, 1637 of them corresponded to known genes (647 of which were up-regulated and 990 down-regulated in the variants spontaneously switching at higher frequencies), including genes known to be involved in regular class switching (such as Cd40, Lig4, H2afx,Ung, Xrcc4, Tcfe2a, Id2, Apex1, Bcl6 and Prdm1) as well as genes involved in processes known to be necessary for regular class switch recombination (CSR), such as transcription, response to DNA damage and DNA repair, DNA binding, chromatin modifications, etc. Two subclones of each hybridoma switching at low (L) and high (H) frequencies were analyzed.
Project description:This is a comparative microarray analysis of 36-65 hybridomas switching at normal low frequencies in vitro vs. selected variants spontaneously switching at 100 fold higher frequencies in vitro. This analysis reveals differential gene expression of 2091 unique probe sets, 1637 of them corresponded to known genes (647 of which were up-regulated and 990 down-regulated in the variants spontaneously switching at higher frequencies), including genes known to be involved in regular class switching (such as Cd40, Lig4, H2afx,Ung, Xrcc4, Tcfe2a, Id2, Apex1, Bcl6 and Prdm1) as well as genes involved in processes known to be necessary for regular class switch recombination (CSR), such as transcription, response to DNA damage and DNA repair, DNA binding, chromatin modifications, etc.
Project description:To more closely reproduce key cellular and stromal features of the desmoplastic reaction of cholangiocarcinoma in vitro, we developed a novel 3-dimensional culture modeling of cancer and stromal cells as a strategy for targeted therapies Cellular, molecular, and functional characterization of different cancer-associated fibroblastic (CAF) and cholangiocarcinoma cell strains isolated from orthotopic tumors arising from bile duct inoculation of spontaneously-transformed rat cholangiocytes (BDEsp cells) in Fischer 344 young adult male rats.
Project description:Expression data from 4T1 subclones derived from mammary fat pad tumors (MFP), axillary lymph node tumors (AxLN), and axillary lymph node-derived lung metastases (AxLN-LuM). In parallel, expression data, in the same subclones, of tail vein-derived (TV) lung metastases. The mechanism of how lymph node metastases seed distant metastases is unknown. We used the 4T1 breast cancer cell line, which is an immune competent model of triple negative breast cancer and spontaneously metastasizes in balb/c mice. 4T1-GFP/fLuc cells were injected into MFP to form tumors and 4T1-mCherry/rLuc cells were injected into axillary lymph nodes to form tumors and then allowed to metastasize to lung. TV cells were allowed to metastasize in the lung. Cells were harvested at different time intervals after the injection. Tumors were extracted, dissociated, and then expanded in vitro to obtain MFP, AxLN, AxLN-LuM and TV-LuM subclones isolated after different time lags with respect to the injection.
Project description:Molecular Characterization of Spontaneously Transformed Epithelial Murine Colon Cell Lines as a Model of Human Colorectal Neoplasia (CGH)
Project description:Molecular Characterization of Spontaneously Transformed Epithelial Murine Colon Cell Lines as a Model of Human Colorectal Neoplasia (expression)
Project description:YTN2 and YTN16 cell lines are subclones established from chemically induced gastric cancer (Yamamoto M et al. Cancer Science 2018). When inoculated to normal C57BL/6 mice, YTN2 spontaneously regresses , while YTN16 grows progressively. To compare expression profiles of these cell lines, we examined microarray analysis.
Project description:Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes. Tumors arising from bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to tumors arising from the inoculation of high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats.
Project description:Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma. We assess transcriptomic and epigenomic changes to resolve the multifactorial nature of therapy resistance and relate it to the parallel occurrence of different mechanisms: (1) preexisting epigenetic profiles of subclones associated with survival advantages, (2) converging phenotypic adaptation of genetically distinct subclones, and (3) subclone-specific interactions of myeloma and bone marrow microenvironment cells. Our study showcases how an integrative multiomics analysis can be applied to track and characterize distinct multidrug-resistant subclones over time for the identification of molecular targets against them.