No description available.

No description available.

No description available.

No description available.

There is no abstract available for this dissertation. / Department of Educational Studies

Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references. / viii, 12 leaves, bound ill. 29 cm

Thesis (MSc.(Pharmacology)--Faculty of Health Sciences)-University of Pretoria, 2008. / Includes bibliographical references.

The synthesis and extensive spectroscopical characterization of novel phthalocyanines are reported. The new compounds were characterized by elemental analysis, FT-IR, ¹HNMR, mass spectrometry and UV–Vis spectroscopy. The new phthalocyanines showed remarkable photophysicochemical behaviour. The novel phthalocyanines were then conjugated to nanoparticles, silver and ZnO. The coupling of the novel Pcs to nanoparticles was through covalent bonding and ligand exchange. These conjugates were supported onto electrospun polystyrene fibers and chitosan microbeads for use as photocatalysts. The efficiency of the immobilized Pcs and Pc-nanoparticles was assessed by the phototrasfromation of organic pollutants, methyl orange and Rhodamine 6G as model dyes. Upon conjugating phthalocyanines to nanoparticles, there was a great increase in the rate of photodegradation of the model dyes. The photodynamic activity of the novel phthalocyanines upon conjugating to nanoparticles and selected targeting agents is also reported. The targeting agents employed in this study are folic acid and polylysine. Conjugating the phthalocyanines to folic acid or polylysine improved the solubility of the phthalocyanines in aqueous media. The potency of the conjugates was investigated on breast (MCF-7), prostate and melanoma cancer cell lines. The phthalocyanines showed no toxicity in the absence of light. However, upon illumination, a concentration dependent cellular decrease was observed.

Breast cancer is the most frequently diagnosed cancer in women worldwide.A treatment regime, both effective and safe and can only be achieved once more effective chemotherapeutic agents are discovered or identified. These “drugs” must selectively induce cell death such as apoptosis or necroptosis in the cancer cells. Apoptotic cell death allows a cell to “commit suicide” in genetically- controlled or programmed mechanism(s). The microenvironment of the tumour is important since a nurturing malignant environment is required for tumour maintenance, progression and ultimately the development of metastasis. Due to the correlation of the tumour microenvironment to aggressive tumour progression, emphasis should be placed on the constituents of the tumour’s microenvironment. In recent years, the understanding of intracellular pathways in cancer cells has increased rapidly, contributing to the development of drugs with more specific targets such as growth factors, signalling molecules, cell adhesion proteins, proteases, cell-cycle proteins, modulators of apoptosis and molecules that promote angiogenesis and metastasis. The main aim of this study was thus to identify a few potential or active compounds from a library of synthetically-derived compounds as possible alternative breast cancer treatment candidates.

Introduction The prognosis in oesophago-gastric cancer is poor with less than 15% patients surviving beyond 5 years after diagnosis. The addition of neoadjuvant therapy has been shown to increase survival in patients suitable for curative surgery. However, the additional gains are modest and the majority of patients do not respond sufficiently from therapy to gain any benefit. There is an urgent need to identify markers that can predict response to neoadjuvant therapy in order provide safer, more effective, individualised treatment regimes. Methods A prospective, multi-centre, collaborative study was undertaken in patients with oesophago-gastric cancer undergoing neoadjuvant therapy and potentially curative surgery. Levels of circulating biomarkers M2-Pyruvate kinase, alkaline phosphatase, CA19-9, CEA and CA 72-4 were measured in patients before and after administering the first cycle of chemotherapy. Binary logistic regression analysis was performed to assess the ability of biomarkers to predict histological response to therapy. Results 165 patients were recruited to the main study. 105 patients had complete histopathological data for analysis. There were 27 responders and 78 non-responders to neoadjuvant therapy. There were no differences in pre-therapy demographic, pathological or treatment factors between the two groups. Responders had less post-operative lymphovascular invasion (P= 0.004) and higher R0 resection rates (P=0.03). Pre-therapy M2-Pyruvate kinase levels were lower in responders compared to non-responders (P=0.037) and levels were able to predict response with each unit increase in the biomarker level being associated with a 4.1% decrease in the likelihood of response (P=0.027). M2-PK levels were not associated with any pre-operative demographic, clinical or pathological factors. Conclusions Pre-therapy dimeric M2-PK levels can predict response to neoadjuvant therapy in patients with oesophago-gastric cancer. The test could be of clinical value for 1 in every 8 patients undergoing the test.