Project description:For identification of candidate genes that is specifically expressed in Ewing family tumor (EFT) cells, we performed DNA microarray-based global expression profiling using Affymetrix Human Genome U133 Plus 2.0 Array and analyxed expression profiles from EFT cell lines (7 lines), neuroblastoma (NB) cell lines (3 lines), a Rhabdomyosarcoma (RMS) cell line, and a human immortalized mesenchymal progenitor cells UET-13 cells. Experiment Overall Design: Expression profiles of pediatric solid tumor cell lines were analyzed and compared using Affymetrix HG-U133 Plus 2.0 (GPL570).
Project description:Characterizing the complex composition of solid tumors is fundamental for understanding tumor initiation, progression and metastasis. While patient-derived samples provide valuable insight, they are heterogeneous on multiple molecular levels, and often originate from advanced tumor stages. Here, we use single-cell transcriptome and epitope profiling together with pathway and lineage analyses to study tumorigenesis from a developmental perspective in a mouse model of salivary gland squamous cell carcinoma. We provide a comprehensive cell atlas and characterise tumor-specific cells. We find that these cells are connected along a reproducible developmental trajectory: initiated in basal cells exhibiting an epithelial-to-mesenchymal transition signature, tumorigenesis proceeds through Wnt-differential cancer stem cell-like subpopulations before differentiating into luminal-like cells. Our work provides unbiased insights into tumor-specific cellular identities in a whole tissue environment and emphasizes the power of using defined genetic model systems.
Project description:We have studied the anti-cancer activities of antofine N-oxide isolated and purified from the medicinal plant Cynanchum vincetoxicum. The compound displays a strong cytotoxic effect on several solid tumor cell lines (glioblastoma, breast carcinoma and lung carcinoma) and on T-cell leukemia. It induces cytostasis in the solid tumor cell lines whereas it causes apoptotic cell death in the leukemia cell line. The cytotoxic effect is much weaker in non-cancer control cells. A microarray analysis of the gene expression after a short treatment showed a set of differentially expressed genes in the two types of cancer cells (apoptosis versus cytostasis). Interestingly, a number of genes of the TNF-alpha signaling pathway are up-regulated in the three solid tumor cell lines, including TNF-alpha which is among the most significantly up-regulated genes. The increased TNF-alpha, TNFAIP3 and BIRC3 mRNA levels were further confirmed after different treatment durations by real-time quantitative PCR (qPCR). Our results suggest that inhibition of cell proliferation in solid tumor cells essentially occurs through TNF-alpha signaling whereas no conclusion could be drawn concerning the pathways leading to apoptotic cell death in leukemia cells due to the reduced number of differentially expressed genes.ヤ
Project description:Current knowledge in three-dimensional (3D) chromatin regulation in normal and disease states was mostly accumulated through Hi-C profiling in in vitro cell culture system. The limitations include failing to recapitulate disease-specific physiological properties and often lacking clinically relevant disease microenvironment. In this study, we conduct tissue-specific Hi-C profiling in a pilot cohort of 12 breast tissues comprising of two normal tissues (NTs) and ten ER+ breast tumor tissues (TTs) including five primary tumors (PTs), and five tamoxifen-treated recurrent tumors (RTs). We find largely preserved compartments, highly heterogeneous topological associated domains (TADs) and intensively variable chromatin loops among breast tumors, demonstrating 3D chromatin-regulated breast tumor heterogeneity. Further cross-examination identifies RT-specific looping-mediated biological pathways and suggests CA2, an enhancer-promoter looping (EPL)-mediated target gene within the bicarbonate transport metabolism pathway, might play a role in driving the tamoxifen resistance. Remarkably, the inhibition of CA2 not only impedes tumor growth both in vitro and in vivo, but also reverses chromatin looping. Our study thus yields significant mechanistic insights into the role and clinical relevance of 3D chromatin architecture in breast cancer endocrine resistance.