Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Keywords: myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, malignant fibrous histiocytoma
Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Experiment Overall Design: Gene expression of 105 soft tissue tumor samples consisting of synovial sarcoma (n=16), myxoid liposarcoma (n=19), lipoma (n=3), well-differentiated liposarcoma (n=3), dedifferentiated liposarcoma (n=15), myxofibrosarcoma (n=15), leiomyosarcoma (n=6), malignant peripheral nerve sheath tumor (n=3), fibrosarcoma (n=4) and malignant fibrous histiocytoma (n=21) were analyzed using an Affymetrix HG-U133A array.
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma. Murine soft tissue sarcomas (n = 17) were compared to normal muscle (n = 4). Tumors were isolated surgically from soft tissue sarcomas generated by conditional Kras and p53 alleles. Tumors were induced using an adenovirus expressing Cre recombinase. Normal muscle samples were isolated from mice of the same genotype without tumor induction.
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma like tumors from BrafCa, p53Fl/Fl mouse model of soft tissue sarcoma
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.
Project description:We are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy. In this study, we studied six MFH tumours, and identified a number of signaling pathways that were consistently activated in the SP population compared to the non-SP population.
Project description:We are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy.
Project description:To investigate the altered patways among sarcomas and MSCs, gene expression profiles were comared among rat osteosarcoma and malignant histiocytoma (MFH) to mesenchymal stem cells (MSCs) from syngeneic origin. Several altered pathways have identified including down-regulation of Wnt, Cell adhesion, ECM interaction and up-regulation of Hedgehog, cell cycling pathways in rat sarcomas compared to MSCs. Gene expression array analysis was perfromed for the samples of rat osteosarcoma COS1NR and malignant fibrous histiocytoma MFH1NR cell lines, bothe established from chemically induced tumors in F344 rats by 4-HAQO, and rat mesenchymal stem cells freshly isolated from femur bone marrow of F344 rats.
Project description:Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers. We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition. Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types. These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.
Project description:This study was performed to identify gene expression differences in not otherwise specified soft tissue sarcomas (NOS, malignant fibrous histiocytomas) and correlate them to histological findings and the clinical course. RNA was isolated and differential gene expression was analysed by the microarray technique. We used microarrays to detail the global gene expression differences between primary soft tissue sarcoma samples, harvested intraoperatively. Keywords: response to chemotherapeutic agent