No description available.

<p dir="ltr">Angiosarcoma (AS) is a rare, understudied cancer that arises from endothelial cells with an extremely poor prognosis. More research is necessary to understand AS pathogenesis, which will lead to the development of novel therapies to improve patient survival. Evidence from our lab highlights the importance of miRNAs in disease progression by demonstrating that endothelial cell-specific loss of mature miRNAs drives AS in mice. Furthermore, individual miRNAs have been characterized as tumor suppressors in AS. Taken together, this underscores the role of miRNAs in AS pathogenesis and suggests that they are an underexplored therapeutic strategy that could be efficacious in treating this cancer. Due to the evidence that miRNA loss is a driver of AS, we hypothesized that global miRNA enhancement would reduce cancer phenotypes. We interrogated this question through the use of a small molecule enhancer of RNAi, enoxacin. We found that enoxacin robustly reduced cancer phenotypes, particularly in AS models driven by miRNA loss, and that enoxacin increased the expression of mature tumor-suppressing miRNAs. We then thoroughly characterized miR-497 in angiosarcoma, demonstrating that miR-497 overexpression ablated tumor formation in mice through the regulation of a network of target genes. Furthermore, we identified <i>Vat1</i> as a novel target gene of miR-497, and found that genetic and pharmacologic inhibition of <i>Vat1</i> reduced cell migration in AS. Overall, this work further highlights the important roles miRNAs play in AS pathogenesis, and points toward miRNAs as an exciting therapy that should be explored further.</p>

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Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22739号 / 医博第4657号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 佐藤 俊哉, 教授 椛島 健治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Malignant vascular tumors of the head and neck are rare neoplasms with variable clinical presentation, wide age distribution, and variable clinical courses. The heterogeneous presentation of angiosarcomas and epithelioid hemangioendothelioma often leads to misdiagnosis and unsuitable treatment. While risk factors for angiosarcomas are previous radiation, chronic lymphedema, and exposure to arsenic, thorium oxide, or vinyl chloride, there are only limited and retrospective data available on prognostic factors in EHE. In both angiosarcomas and EHE, surgery is the mainstay of treatment. There is limited evidence regarding the role of radiotherapy in EHE, although EHE is considered relatively radiosensitive. In angiosarcomas, adjuvant radiotherapy is recommended according to retrospective case series. A standard medical therapy for metastasized malignant vascular tumors is lacking. Chemotherapy, which is effective in angiosarcoma, is mostly ineffective in EHE. Targeted therapy, antiangiogenetic drugs and immunotherapy have been studied as new treatment options. The goal of this review is to summarize the current data regarding malignant vascular tumors along with their diagnosis and management.