Oxygen supports the life of all aerobic organisms and virtually every cell type is capable of sensing decreased tissue oxygenation, known as hypoxia. Hypoxic microenvironments have been detected within developing solid tumors as a result of insufficient host vascular delivery of oxygen and nutrients. Consequently, the formation of solid tumors requires the coordination of angiogenesis: the recruitment of blood vessels for the purpose of tumor vascularization. Furthermore, clinical and experimental evidence have demonstrated that hypoxic cells in solid tumors can limit the efficacy of standard anticancer therapeutics including radiotherapy and chemotherapy. Low oxygenation can also accelerate malignant progression and metastasis resulting in poorer prognosis irrespective of the chosen treatment regiment. It is the focus of our research to improve our understanding of the molecular events that support the development of tumor cell resistance to hypoxia as a tool for the discovery of effective therapeutics that can specifically and effectively target hypoxic tumors. Understanding exactly how tumor cells adapt to transient hypoxia could lead to the identification of novel therapeutic targets that in combination therapy with current anticancer treatments could help reduce the incidence of morbidity and mortality from cancer.

A decision whether to receive chemotherapy for stage IV non-small cell lung cancer (NSCLC) is one in which the benefits and risks of the treatment and the personal values of the patient must be considered. Objectives of the study were to develop and conduct a preliminary evaluation of a decision aid for patients making the decision about chemotherapy for stage IV NSCLC. In particular, this study: (1) evaluated the effect of the decision aid on the patient's comprehension of the treatment alternatives, benefits and risks; (2) evaluated the effect of the decision aid on the decisional conflict experienced by the patient; and (3) evaluated the decision aid's acceptability to patients and practitioners. The decision aid was developed by Valerie Fiset, Dr Annette O'Connor, Dr Bill Evans, Dr Jo Logan and Cathy DeGrasse. It includes information describing advanced lung cancer, its effects and what people may do to cope with those effects. As well, the decision aid describes supportive care, radiation therapy, and chemotherapy, discussing in detail the benefits and risks of chemotherapy. The last part of the decision aid is an exercise in values clarification, which helps the patient to think about what is most important to them in making the decision about chemotherapy. (Abstract shortened by UMI.)

Kaposi's sarcoma (KS) is a multifocal proliferative disorder that is commonly associated with individuals who suffer some degree of reduction in immune competence. Therapy for this disorder varies and is determined by the seriousness of KS disease in the patient as well as the patient's ability to tolerate the different treatments. A better understanding of how KS arises would allow investigators to tailor therapies that would be more specific to KS and less detrimental to the individual. In this work, cell lines were established from skin biopsies taken from KS lesions of individuals with AIDS. The KS1 cell line presented as a combination of adherent and non-adherent cells that proliferated aggressively without senescence. The KS4 cell line presented as the typical spindle cell population that proliferated aggressively, but eventually senesced. Both cell lines were positive for the presence of Factor VIII-related antigen (FVIII) and the production of IL-6 and basic Fibroblastic Growth Factor (bFGF). When the association with Human Herpesvirus 8 (HHV8) was assessed, the virus proved undetectable in both cell lines. The response of the KS cell lines to Doxorubicin, Etoposide, and ALX40-4C was assessed. (Abstract shortened by UMI.)

Our laboratory has been interested in factors in the tumour microenvironment that may contribute to mutagenesis, and thus lead to tumour progression. The well documented relationship between chronic inflammatory states and cancer implicates inflammatory cells, such as macrophages and neutrophils, and their products as having a role in carcinogenesis. Using the MN-11 system, an in vitro/in vivo murine tumour model developed in our laboratory, the mutagenicity of neutrophils and one of their products, reactive nitrogen species, was studied. To further investigate the mechanism of the observed mutagenicity of nitric oxide donors on MN-11 cells, cellular glutathione levels of cells treated with glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) were manipulated. Reactive nitrogen species, such as nitric oxide, are part of the microbicidal armament of neutrophils. Neutrophils have been implicated as a possible link between chronic inflammation and cancer, and are the most abundant inflammatory cell type observed in MN-11 tumours. Thus, the role that neutrophils have in causing mutations was investigated. (Abstract shortened by UMI.)

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