Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 111-127). Also available on the Internet.

Thesis (M.D.)--University of Hong Kong, 1995. / "September 1994." Includes bibliographical references.

Thesis (doctoral)--Uppsala University, 1981. / At head of title: From the Department of Oncology, Division of Gynecologic Oncology, University Hospital, Uppsala, Sweden. Bibliography: p. 29-34.

Diss. med. dent. Zürich. / Literaturverz.

Diss. med. dent. Zürich. / Literaturverz.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.D.)--University of Hong Kong, 1995. / "September 1994". Includes bibliographical references. Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Emerging from potentially malignant disorders that in most cases will never become cancerous, head and neck squamous cell carcinoma (HNSCC) is a cancer that is extremely difficult to diagnose early. This late stage diagnosis has allowed limited improvements in overall survival (OS) as patients are prone to local recurrence, secondary primary tumors, and distant metastasis. As a result, it has become vitally important to assess the prognostic value of biological marker screening to provide an avenue for early diagnosis and identification of local recurrence or residual secondary tumor sites. Many characteristic markers such as EGFR, p16, p53 and VEGF that are constitutively mutated in HNSCC have been identified. However, the dysregulation of VEGF marks a landmark mutation that accelerates the diseases progression and spread. An angiogenic protein normally expressed in response to hypoxic conditions, VEGF allows the creation of new vasculature to remove catabolites and bestows resistance to normal cellular apoptotic signals; pathways often employed by chemotherapeutics. Therefore, early identification of VEGF poses a unique opportunity to employ aggressive therapeutic regimens in combination with precision surgical resection to eliminate the cancer before neovascualture invasion has occurred and the tumor has expanded significantly. For this reason, this review will examine the current literature available on VEGFs role in HNSCC, its value as a prognostic marker.

Bisphosphonates (BPs) have been used clinically as anti-resorptive/cancer agents with confounded clinical outcomes and uncertain/conflicting biological understanding. This study was designed to evaluate the impact of clinically used anti-resorption drug alendronate (ALN) on cancer-bone metastasis and bone biology using novel 3D cancer-bone interaction model systems. To test the effects of ALN on the cancer-bone metastasis/interactions and bone biology we have utilized a novel 3D Co-cultures of live mouse neonatal calvarial bone organs with oral squamous cancer cells in a roller tube model systems (Curtin et al, 2012) in the absence and presence of ALN. These model systems under bone resorption and formation conditions were evaluated by chemical, biochemical, and histological analyses of the used media and calvarial bones. At the end of 8 days, the calvarial bones co-cultured with oral cancer cell lines in the absence and presence of ALN were processed for histological observations, TRAP and ALP enzyme activities, and neutral red staining. These studies were complemented by the effects of ALN on oral cancer cells under 2D classic cell culture conditions. In 3D-bone organ cultures under resorption conditions, oral cancer cells induce differentiation of osteoclasts and bone resorption and inclusion of ALN inhibited cancer-induced bone resorption. However, in both bone resorption and formation models the oral cancer cells colonized the bone and while treatment with ALN inhibits bone resorption, no effect on bone colonization was evident. Contrary to those under 2D cell culture conditions exposure to ALN of confluent and non-confluent oral cancer cells in the absence of live bone impacted oral cancer cells significantly in a dose dependent manner. Our studies using live bone organ cultures with oral cancer cells under specific dissociated bone remodeling stages, viz., resorption or formation only, revealed major and significant biological events which led to the conclusions that: (a) In the absence of bone in 2D cultures oral cancers are sensitive to ALN treatment whereas in the 3D live bone microenvironment tumors are resistant to ALN drug therapy, and (b) oral cancer-bone metastasis is independent of bone remodeling stage.