The study of the processes relating glycobiology and cancer will have increased interest in coming years. To contribute to this trend the outcome of this work will be useful for investigations in glycobiology, using experimental methods exhibiting controlled carbohydrate composition, organization, and orientation, drawn from materials science and physics and that can be used in bioengineering and other technical areas in biology. In this work, the focus has been on physical studies of some members of the family of glycosaminoglycans and their role in cancer metastasis. The project studies the static adhesion of cancer cells to substrates functionalized with cell surface glycocalyx molecules and, in particular, in the interaction of heparan sulfate, keratan sulfate and chondroitin sulfates with the cells. Surface characterization techniques are used to analyze the structure of the polymeric brushes deposited on the substrates. The hypothesis that the adhesion of whole cancer cells to glysocaminoglycan substrates is a function of polysaccharide charge per dimer and chain length was proposed and tested.Part of the work has been dedicated to study the changes in the adhesion of tumor cells inthe presence of heparanase, an enzyme expressed in the tumor cell surface.The essential achievements of the project have been: a) Design of a new a method for the deposition and patterning of glycans to glass or silicon surfaces functionalized with a silane agent, exposing an amino terminated monolayer as functional substrate. b) Development of a new method for the calculation of the density of the deposited molecules. c) Physical characterization of the surfaces using a combination of surface science techniques, including ellipsometry and atomic force microscopy. These surfaces should be useful for developing additional experiments that may be helpful in understanding the adhesive properties of the cells. d) Comparative analysis of the behavior of cancer cells to the functionalized surfaces, specifically the study of the static adhesion of the cells, in the presence or absence of the surface protein heparanase or its inhibitors. e) Confirmation of the hypothesis that attachment of whole cancer cells, in vitro, depends linearly on the charge per dimer of polysaccharide.

Thesis (M.S.)--Mississippi State University. Department of Agricultural and Biological Engineering. / Title from title screen. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 108-124). Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 108-124). Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 149-163). Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 149-163). Also available in print.

published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Chondroitin sulphate proteoglycans (CSPGs) from the glial scar inhibit axonal regeneration following spinal cord injury. CSPG expression can be induced by transforming growth factor β (TGFβ), which suggests that inhibition of TGFβ may reduce CSPG levels. Astrocytes were treated with cyclic AMP (cAMP), which reduced TGFβ signaling protein Smad2 in astrocytes. However, cAMP-treated astrocytes showed strong neurocan expression following TGFβ treatment, which suggests that TGFβ may mediate CSPG expression through non-Smad pathways. Smad2 or Smad4 were knocked down in astrocytes using siRNA and TGFβ-induced neurocan, brevican and aggrecan expression were still observed, indicating that Smad signaling is not required for CSPG expression. Administration of a PI3K/Akt inhibitor produced significant reductions in neurocan, brevican and aggrecan expression in astrocytes, which suggests that PI3K/Akt pathway mediates CSPG expression. Erk1/2 inhibitor treatment did not reduce CSPG expression significantly. Targeting non-Smad signaling pathways may therefore be effective strategies to reduce CSPG expression following injury.

Offprints of the author's articles inserted / Bibliography: leaves 230-265 / List of the author's publications: leaves 266-263 [i.e. 267] / 263 [i.e. 268] leaves : ill. (1 col.) ; 31 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Dental Science, 1984

Dissertation Thesis (Ph.D.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 202 pages. Includes vita. Includes bibliographical references.