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:CD47 is a “don’t eat me” signal that is frequently overexpressed in tumors to evade phagocytosis by tumor associated macrophages (TAM). Investigational agents targeting CD47, such as magrolimab, aim to induce phagocytosis of tumor cells by TAMs. Previously, two functionally defined key TAM subsets have been identified: complement C1q C chain positive (C1QC) TAMs, which display pro-phagocytic activity, and secreted phosphoprotein 1 positive (SPP1) TAMs that express pro-angiogenic markers. Here we characterize CD47 expression and its relationship with tumor macrophages in solid tumor samples.
Project description:Hi-C sequencing is a DNA-based next-generation sequencing method that preserves the 3D genome conformation and has shown promise in detecting genomic rearrangements in translational research studies. To evaluate Hi-C as a potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia and sarcoma specimens. Archived viable and non-viable frozen leukemic cells and formalin-fixed paraffin-embedded (FFPE) tumor specimens were analyzed. Pediatric acute myeloid leukemia (AML) and alveolar rhabdomyosarcoma (A-RMS) specimens with known genomic rearrangements were subjected to Hi-C to assess analytical concordance. Subsequently, a discovery cohort consisting of AML and acute lymphoblastic leukemia (ALL) cases without known genomic rearrangements based on prior clinical diagnostic testing was evaluated to determine whether Hi-C could detect rearrangements. Using a standard sequencing depth of 50 million raw read-pairs per sample, or approximately 5X raw genomic coverage, we observed 100% concordance between Hi-C and previous clinical cytogenetic and molecular testing. In the discovery cohort, a clinically relevant gene fusion was detected in 45% of leukemia cases (5/11). This study provides an institutional proof of principle evaluation of Hi-C sequencing to medical diagnostic testing as it identified several clinically relevant rearrangements, including those that were missed by current clinical testing workflows.