Annexin A1 (AnxA1) is a candidate regulator of the epithelial-to mesenchymal (EMT)-like phenotypic switch, a pivotal event in breast cancer progression. We show here that AnxA1 expression is associated with a highly invasive basal-like breast cancer subtype both in a panel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdown in invasive basal-like breast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancing TGFβ/Smad signaling and actin reorganization, which facilitates an EMT-like switch, thereby allowing efficient cell migration and invasion of metastatic breast cancer cells.
Mutations in SOX18, VEGFC and Vascular Endothelial Growth Factor 3 underlie the hereditary lymphatic disorders hypotrichosis-lymphedema-telangiectasia (HLT), Milroy-like lymphedema and Milroy disease, respectively. Genes responsible for hereditary lymphedema are key regulators of lymphatic vascular development in the embryo. To identify novel modulators of lymphangiogenesis, we used a mouse model of HLT (Ragged Opossum) and performed gene expression profiling of aberrant dermal lymphatic vessels. Expression studies and functional analysis in zebrafish and mice revealed one candidate, ArfGAP with RhoGAP domain, Ankyrin repeat and PH domain 3 (ARAP3), which is down-regulated in HLT mouse lymphatic vessels and necessary for lymphatic vascular development in mice and zebrafish. We position this known regulator of cell behaviour during migration as a mediator of the cellular response to Vegfc signalling in lymphatic endothelial cells in vitro and in vivo. Our data refine common mechanisms that are likely to contribute during both development and the pathogenesis of lymphatic vascular disorders.
The Republic of Suriname (South America) is located on the Guiana Shield, one of the regions with the highest biodiversity and the largest expanse of undisturbed tropical rain forest in the world. The population of almost 570,000 consists of a unique blend of ethnic groups and cultures from all continents. These include Indigenous Amerindians, the original inhabitants; Maroons, the descendants of runaway slaves who had been shipped from Africa between the seventeenth and the nineteenth century; Creoles, a generic term referring to mixed blacks and whites; the descendants from indentured workers from China, India, and Java (Indonesia) who arrived between the second half of the nineteenth and the irst half of the twentieth century; as well as immigrants from various Middle Eastern, European, Caribbean, and South American countries. All these groups have made their own speciic contribution to Suriname's traditional medicine, which has resulted in a myriad of remedies against many disorders, mainly employing a variety of plants. This chapter presents a brief history of Suriname, addresses the ethnopharmacological practices of Maroons and Creoles as well as Hindustanis and Javanese, and concludes with a few remarks on the previsions provided by the country's rich plant-based traditional medicine.
Substances from terrestrial plants and marine organisms have since long been recognized as important sources of bioactive substances. This has led to the development of a large variety of drugs to treat human diseases such as, among others, a number of antihypertensive, hypoglycemic, cardiovascular, antibiotic, and antineoplastic agents. More recently, the amazing biodiversity represented by the myriad of insect species has been realized to produce an equally exceptional source of bioactive chemicals with therapeutic potential. Many of these compounds serve as highly effective defensive and predatory chemicals and have enabled insects to survive for hundreds of millions of years and to diversify to the countless different species known today. As some of these chemicals possess meaningful pharmacological properties, they represent interesting candidates for new drug discovery and development programs. A few examples are substances with microcidal, cytotoxic, cytolytic, apoptotic, anti-angiogenic, or anticoagulant qualities. This paper addresses the significance of bioactive compounds from insects as lead compounds for producing new therapeutics.
This thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis. I have clearly stated the contribution of others to my thesis as a whole, including statistical assistance, survey design, data analysis, significant technical procedures, professional editorial advice, and any other original research work used or reported in my thesis. The content of my thesis is the result of work I have carried out since the commencement of my research higher degree candidature and does not include a substantial part of work that has been submitted to qualify for the award of any other degree or diploma in any university or other tertiary institution. I have clearly stated which parts of my thesis, if any, have been submitted to qualify for another award. I acknowledge that an electronic copy of my thesis must be lodged with the University Library and, subject to the General Award Rules of The University of Queensland, immediately made available for research and study in accordance with the Copyright Act 1968.
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