"July, 2003" / "Amendments of the thesis" and "abbreviations (additional)" inside back cover. / Includes bibliographical references (leaves 195-231) / x, 231, [20] leaves : ill., plates ; 30 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 Paediatrics, 2003

Thesis (Ph.D.)--University of Toledo, 2006. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Major advisor: Brian G. Rowan. Includes abstract. Document formatted into pages: iv, 204 p. Title from title page of PDF document. Title at ETD Web site: Molecular mechanisms of protein kinase a signaling pathway on estrogen receptor action in breast cancer . Bibliography: pages 59-65, 100-104, 137-150, 167-202.

<p><strong>Background                      </strong></p><p>There are different types of treatments for breast cancer, and these may be of surgical and non-surgical art. These treatments produce different side effects that can cause both physical and mental harm to the woman. The breast cancer can change the women's body image and relationships to their families. The women manage their lives in different ways depending on which culture they belong to. <strong></strong></p><p><strong>Aim                                    </strong></p><p>The aim of the study was to elucidate women’s experience of her body and the altered body in relation to breast cancer treatment.</p><p><strong>Method                              </strong></p><p>The method used was a literature review based on scientifically articles to overview the field of breast cancer. For the systematic and unsystematic search nine articles were found and used to present the results. <strong></strong></p><p><strong>Results                               </strong></p><p>The result was based on analyzes of the nine articles and three main themes revealed: To take control, To change and To meet the cultural ideal. <strong></strong></p><p><strong>Conclusion                         </strong></p><p>Women with breast cancer often experience hair loss as the most difficult part of the treatment. It’s therefore important that the women is prepared to what is going to happen for being able to handle the new situation. By preparing in different ways women handle their situation easier. It’s important for the women to feel normal and maintain their identity and role in the family. </p>

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 115-122.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 70-81.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 128-138.

Background                      There are different types of treatments for breast cancer, and these may be of surgical and non-surgical art. These treatments produce different side effects that can cause both physical and mental harm to the woman. The breast cancer can change the women's body image and relationships to their families. The women manage their lives in different ways depending on which culture they belong to. Aim                                    The aim of the study was to elucidate women’s experience of her body and the altered body in relation to breast cancer treatment. Method                              The method used was a literature review based on scientifically articles to overview the field of breast cancer. For the systematic and unsystematic search nine articles were found and used to present the results. Results                               The result was based on analyzes of the nine articles and three main themes revealed: To take control, To change and To meet the cultural ideal. Conclusion                         Women with breast cancer often experience hair loss as the most difficult part of the treatment. It’s therefore important that the women is prepared to what is going to happen for being able to handle the new situation. By preparing in different ways women handle their situation easier. It’s important for the women to feel normal and maintain their identity and role in the family.

Syftet med studien var att beskriva hälsorelaterad livskvalitet, ångest/depression och vårdtillfredsställelse hos kvinnor med bröstcancer tidigt i sjukdomsförloppet samt att undersöka om det fanns ett samband mellan dessa aspekter. Vidare studerades förklarande bakgrundsfaktorer; demografiska, socioekonomiska och medicinska faktorer samt psykosocialt stöd. Denna tvärsnittsstudie genomfördes som en enkätstudie kompletterat med medicinska data från Regionalt register för bröstcancer i Uppsala/Örebroregionen. Totalt 1574 förfrågningar om deltagande gick ut, varav 69 % valde att delta i studien. Niohundratrettiotvå kvinnor ingick i de slutliga analyserna (59 %). Kvinnorna besvarade en enkät med instrument som mäter hälsorelaterad livskvalitet, ångest/depression och vårdtillfredsställelse samt frågor kring demografiska och socioekonomiska aspekter, psykosocialt stöd och komorbiditet. Data analyserades med uni-, bi- och multivariata analyser. Resultaten visade att bröstcancerpatienterna upplevde problem med global hälsostatus, roll-, emotionell, social och sexuell funktion och olika symptom samt att en relativt liten andel hade ångest och depression. Det fanns en hög grad av tillfredsställelse med vården, vilket var relaterad till en lägre grad av ångest och depression samt en bättre hälsorelaterad livskvalitet. Skillnader i hälsorelaterad livskvalitet och ångest/depression kunde förklaras av ålder, cytostatikabehandling, komorbiditet, psykosocialt stöd samt sjukskrivning/sjukbidrag, medan enbart en liten andel av variansen i vårdtillfredsställelse kunde förklaras av bakgrundsfaktorer. / The aim of the study was to explore health-related quality of life, anxiety/depression, and patient satisfaction among women with breast cancer early on in the course of the disease, and to investigate correlations between these aspects. Furthermore, the influence of background factors was examined; demographic, socioeconomic, and medical factors, and psychosocial support. This cross-sectional study was carried out as a questionnarie study supplemented with medical data from the Regional Breast Cancer Register of the Uppsala/Örebro Region. A total of 1574 inquiries of engaging in the study were sent out, whereof 69 % accepted. In the final analysis 932 women were included (59 %). Participants completed a questionnaire including instruments measuring health-related quality of life, anxiety/depression, and patient satisfaction, as well as questions regarding demographic and socioeconomic aspects, psychosocial support, and comorbidity. Univariate, bivariate, and multivariate methods were used for data analysis. The results showed that the women experienced problems related to global health status, role, emotional, social, and sexual function, and diverse symptoms, and a relatively small part were defined as clinical cases of anxiety and depression. There was a high degree of patient satisfaction, which in turn was related to less anxiety and depression and a better health-related quality of life. Age, treatment with chemotherapy, comorbidity, psychosocial support, and sick leave/temporary disability pension were shown to influence health-related quality of life and anxiety/depression, whereas only a small part of the variance in patient satisfaction could be explained by background factors.

Despite the common usage of high-dose vitamin C among breast cancer patients, the published medical literature is not in agreement as to how mega-dose vitamin C may interact with conventional therapy to affect clinical outcomes. The purpose of this study was to investigate the interaction of mega-dose vitamin C with radiation therapy and with doxorubicin in the treatment of breast cancer. Cultures of EMT6 mouse mammary tumor cells were treated concurrently with varying dose of vitamin C and either radiation or doxorubicin. A clonogenic assay was then performed to determine the surviving fraction of the cells. The surviving fractions of cells in cultures receiving different doses of vitamin C were compared among themselves as well as with controls and dose response curves were generated. Results show that ascorbic acid administered in concentrations of 1 mM or 10 mM 4 hours before x-irradiation protected the cells from radiation-induced cytotoxicity. The dose-modifying factors for 1 mM and 10 mM ascorbic acid as compared to controls were 1.23 and 1.37 respectively. These results support the hypothesis that mega dose vitamin C, when taken concurrently with radiation therapy, protects cancer cells from the cytotoxic effects of ionizing radiation. No evidence was found to suggest that mega-dose vitamin C alters the antineoplastic effects of doxorubicin.

The therapeutic potential of a novel multi-targeted small-interfering RNA (siRNA) was investigated in human breast cancer cells. Previous studies had identified an siRNA that specifically and potently inhibited expression of thymidylate synthase (TS) by directly targeting human TS mRNA. TS is a folate-dependent enzyme that catalyzes the key reaction involved in synthesizing nucleotide precursors for DNA biosynthesis, and as such, it plays a critical role in maintaining cell growth. The goal of this thesis was to design and develop a novel siRNA molecule that targeted TS mRNA as well as a cellular mRNA that encodes a different cellular protein involved in cancer cell growth and proliferation, such as a member of the ErbB family. Gene sequence analysis was performed and identified an overlapping sequence between TS and ErbB2 mRNAs. An siRNA duplex was then designed to simultaneously target human TS and ErbB2 mRNA. Transfection of the multi-targeted siRNA (TS1M17) revealed that both ErbB2 and TS proteins were significantly suppressed in a time and dose-dependent manner in ErbB2-overexpressing human breast cancer SKBR3 cells. The corresponding mRNA levels, as determined by RT-PCR, were also decreased. Protein levels of other ErbB family members, including ErbB1 and ErbB3, remained unchanged with siRNA treatment. An ErbB2-specific siRNA (B2450) inhibited ErbB2, but had no effect on TS expression demonstrating the specificity of the multi-targeted siRNA against both TS and ErbB2. Mismatched (TS1-Mismatch) and control (GL2) siRNAs had no inhibitory effects on expression of the two target proteins. Suppression of activated ErbB2, as determined by expression of phosphorylated ErbB2 protein, was observed with transfection of TS1M17 siRNA. In addition, the expression of downstream signaling proteins, such as phosphorylated mitogen activated protein kinase (p-MAPK), p27Kip1, p21Cip1, cyclin D1, and survivin were significantly changed. In contrast, control siRNAs did not exert any inhibitory effects on downstream signaling. Taken together, these findings suggest that TS1M17 siRNA inhibits signaling of the ErbB2 pathway. The effect of TS1M17 siRNA on cytotoxicity was analyzed by WST-1 assay. Upon transfection into SKBR3 cells, the TS1M17 siRNA significantly suppressed cell proliferation with an IC50 value of 0.65 nM, which is 154-fold more potent than ErbB2- and TS-specific siRNAs. This study suggests that targeting expression of ErbB2 and TS, two key proteins involved in distinct and critical pathways for cancer growth and proliferation, with a single siRNA molecule may provide a novel approach for cancer chemotherapy.