The present thesis consists of three thematic parts in relation to breast cancer: (a) practice of breast self - examination (BSE), (b) screening mammography attendance and (c) adjustment to breast cancer surgery / mastectomy. The aims of the respective studies are (a) to examine attitudes, beliefs and practices regarding BSE in younger (30 years old or under) and older women (over 30 years old), (b) to explore attitudes and beliefs regarding mammography and identify factors associated with screening mammography attendance and (c) to explore factors associated with adjustment to breast cancer surgery. The above aims are explored in two different cultural contexts, by comparing samples from Scotland and Greece. Samples consisted (a) of 205 younger and 258 older women, university staff and students in Scotland and 85 younger women, university students in Greece, (b) 283 women who attended and 72 women who did not attend the National Breast Screening in Scotland, and 72 women undergoing mammography in Greece and (c) 19 women in Scotland and 27 women in Greece, who have undergone surgery for breast cancer. All participants were assessed on a variety of measures. These included demographics, health history, health beliefs and health - related personality variables. Results indicated that: 1. BSE was predicted by different variables across age and cultural groups. 2. In particular, practice of BSE in younger women was predicted by knowledge about breast cancer, perceived barriers, health motivation and cues for action, whereas practice in older women was predicted by knowledge about BSE, perceived barriers and cues for action. 3. BSE rates in both countries were higher than previously reported but did not differ between women in Scotland and Greece. However, the two groups differed in knowledge and attitudes, regarding BSE, and in personality. Women in Scotland appeared more knowledgeable regarding BSE, felt less susceptible to breast cancer and were less active in coping with health issues than women in Greece. Women in Greece valued their health more and scored higher in chance health locus of control beliefs than women in Scotland. 4. The best predictor of breast screening mammography attendance in Scotland was knowledge about mammography. Attenders appeared to have more knowledge about breast cancer and about mammography and to focus more on emotional coping, in order to deal with health stresses. 5. The two cultural groups differed in health-related decision making and health - related coping styles. Attenders in Scotland were more knowledgeable about risk factors related to breast cancer and about mammograms and perceived significantly more pain/discomfort associated with the procedure, than attenders in Greece. Attenders in Greece resorted more to acceptance and denial and were more likely to seek emotional support, in order to cope with health stressors than attenders in Scotland. 6. Health beliefs of breast cancer patients, in relation to their condition, and their style of coping with threatening information, concerning their breast problem, are highlighted as important factors to their adjustment in both cultures. However, adjustment to breast cancer surgery appears culture-specific, as different factors seem to determine it in different cultural contexts. 7. Patients in Scotland and Greece did not differ in their overall adjustment. However, Greek patients were significantly less well adjusted sexually postoperatively than patients in Scotland. Findings are discussed in relation to theoretical and practical implications.

This thesis describes the design of a virotherapy strategy capable of destroying both breast cancer vasculature and tumour cells, using an oncolytic adenovirus expressing angiogenesis-regulating proteins. Five oncolytic adenoviruses were compared to identify the best virotherapy agent for breast cancer, including measurement of cytotoxicity in vitro, and replication, intra-tumoural spread and anticancer efficacy in vivo. The viruses tested were Ad-dl922-947 (targets G1-S checkpoint defects); Ad-Onyx-015 and Ad-Onyx-017 (target p53/mRNA nuclear export defects); Ad-vKH1 (targets Wnt pathway defects) and AdEHE2F (targets estrogen receptor/G1-S checkpoint/hypoxia signalling defects). AdEHE2F demonstrated optimal oncolytic activity and selectivity against breast cancer, accordingly this virus was engineered to express potent regulatory angiogenic proteins, namely soluble Flt1 and soluble Delta like-4 (Dll4). sFlt1 is the soluble extra-cellular domain of VEGFR1 and binds to and sequesters VEGF-A, thereby preventing VEGFR2 stimulation which is crucial to trigger angiogenesis. sDll4 is the soluble extracellular domain of Dll4 and has been previously shown to block Dll4/Notch signalling. Dll4/Notch signalling increases a chaotic and non-functional angiogenesis which ultimately delays tumour growth. Importantly, VEGF and Dll4 are the only angiogenesis genes reported to be haploinsufficient in vascular development and both have been shown to have a good anti-tumour effect. sFlt1 and sDll4 genes were substituted for the viral genes E3 6.7K/gp19K of AdEHE2F, thereby using endogenous adenoviral machinery to drive production. The activities of AdEHE2F viruses expressing either sFlt1 or sDll4 were compared in vitro and in vivo. sFlt1 (expressed from AdEHE2F) inhibited endothelial cell proliferation and sprouting whereas sDll4 increased proliferation and branching in vitro. In vivo AdEHE2F expressing sFlt1 or sDll4 both showed superior anticancer activity compared to parental AdEHE2F, indicating at least additive efficacy between virotherapy and regulatory angiogenic approaches.

The thesis The analysis of genetic factors of breast cancer by NGS deals with the current serious problematics of breast cancer from the perspective of genetic predisposition. Breast cancer is one of the most common tumors in women. Every year more than 7000 women are diagnosed with this disease and the mortality rate in the Czech Republic is nearly 2000 cases. Of the total number of patients diagnosed with breast cancer, approximately ten percent of patients have congenital mutations in one of the predisposing genes that cause a significantly increased risk of developing a cancer. More than half of these mutations occur in germline mutations of the BRCA1 or BRCA2 genes, others include a number of other genes, eg tp53, CDH1, PTEN, STK11, ATM, PALB2, CHEK2.Early diagnosis and identification of persons with increased risk of developing breast cancer is of key importance for their inclusion in preventive programs. Therefore, the thesis aims to testing genes that can cause a breast cancer. In the thesis, 219 known and candidate predisposition genes were analyzed in a group of 263 non-selected breast cancer patients using a targeted panel NGS, the Illumina platform. Selected identified suspect variants were further confirmed by Sanger sequencing. The aim of this work was also a mutational analysis of...

Single nucleotide polymorphisms present in the second intron of the fibroblast growth factor receptor 2 (FGFR2) gene have been linked with increased risk of breast cancer in several genome wide association studies. The potential effect of those SNPs appeared to be mediated through the differential binding of cis-regulatory elements, such as transcription factors, since all the SNPs in linkage disequilibrium were located in a regulatory DNA region. Preliminary studies have shown that a Runx2 binding site is functional only in the minor, disease associated allele of rs2981578, resulting in increased expression of FGFR2 in cancers from patients homozygous for that allele. Moreover, the increased risk conferred by the minor FGFR2 allele is associated most strongly in oestrogen receptor alpha positive (ERα) breast tumours, suggesting a potential interaction between ERα and FGFR signalling. Here, we have developed a human cell line model system to study the effect of those SNPs on cell behaviour. In an ERα positive breast cancer cell line, rs2981578 was edited using Zinc Finger Nucleases. Unexpectedly, the acquisition of the single risk allele in MCF7 cells failed to affect proliferation or cell cycle progression. Binding of Runx2 to the risk allele was not observed. However FOXA1 binding, an important ERα partner, appeared decreased at the rs2981578 locus in the risk allele cells. Additionally, differences in allele specific expression (ASE) of FGFR2 were not observed in a panel of 72 ERα positive breast cancer samples. Thus, the apparent increased risk of developing ERα positive breast cancer is not caused by rs2981578 alone. Rather, the observed increased risk of developing breast cancer might be the result of a coordinated effect of multiple SNPs forming a risk haplotype in the second intron of FGFR2.

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references (leaves: 49-50)

Cancer is one of the greatest causes of death in modern societies, affecting over 350,000 new cases every year in the UK. Although there are currently more than 100 different cancer types, breast and prostate cancer remain the most common types for women and men respectively. A number of different cancer types follow, with bladder cancer being the ninth most significant type, accounting for 3% of the total new cases. The currently employed techniques aim to diagnose the cancer at an early stage, where the symptoms are easier to be treated and the disease more likely to be cured. A further issue is that many cancers diagnosed will not affect a patient in their lifetime. The current gold standard for cancer diagnosis, biopsy followed by histopathology, is an invasive, restrictive technique and the screening tests suffer from low specificity, the need for a novel diagnostic concept is vital. Furthermore, the current clinical approach does not identify those patients most at risk of advancing disease. A promising approach consists of molecular vibrational spectroscopy techniques, which are based on the interactions of light with matter. One of these is Raman spectroscopy, a technique with wide applications in research and industry, which has the advantage of being non-invasive and chemically highly specific. In this thesis we explore the potential of a group of minimally invasive diagnostic techniques, based on Raman scattering, for prostate, breast and bladder cancer. In the case of the two most prevalent types of cancer, prostate and breast cancer, deep Raman spectroscopy has been employed to study the origin of Raman scattering (Chapters 5 and 6) in animal tissue and tissue phantoms, containing highly scattering materials resembling suspicious features found in tissues (calcifications). The spatial distribution of the Raman signal through the sample volume has been studied in relation to the optical properties and the composition of the sample, showing that a couple of transmission measurements would potentially cover the measuring volume of prostate of typical dimensions. Deep Raman measurements were also extended to animal and human tissue samples, in order to investigate the feasibility of collecting Raman scattering from human prostate tissue and its major tissue components (Chapter 6). Further improvements on these measurements were attempted by introducing the ‘’photon diode’’ element (Chapter 7) in order to achieve signal enhancement, which proved to be in the range of ×1-2.4, depending on the optical properties of the tissue and the depth of the probing element. The same ‘’photon diode’’ concept was utilised to attempt depth prediction of a calcification feature in sample volume (Chapter 8). Regarding bladder cancer, the minimally invasive approach adopted was Raman spectroscopy on urine samples, rather than deep Raman spectroscopy. Raman microscopy was employed in order to discriminate pathological features of bladder cancer between healthy and malignant urine samples. For that reason, the potential differences in urea’s distribution and interactions in urine from healthy and patients with bladder cancer were studied, resulting in promising diagnostic values (73% sensitivity, 80% specificity). The results presented in this thesis are expected to lead to a better understanding of the Raman scattering signals collection through biological tissues and help in this way the future design of Raman instruments aiming to target disease specific signals. This study shows promise for future application of Raman spectroscopy and paves the way towards the future integration of Raman spectroscopy in a non-invasive cancer diagnosis.

This diploma thesis deals with various ways of treatment of selected oncological diseases and the effectiveness of treatment methods and evaluation of the influence of various factors influencing the survival of patients. The activity of individual healing processes is evaluated by survival analysis. The subjects of the study are patients with breast, lung and prostate cancer. The survival analysis considers the sex of the patient, the age and stage of his illness, and other factors to avoid distorted results. The aim of the work is to find out the effects of selected therapeutic procedures on patients' health and to identify factors that have a significant impact on the survival of patients. The data for the diploma thesis was provided by the Institute of Health Information and Statistics of the Czech Republic, the Statistical Office, the National Cancer Register (NOR), the US SEER database and the German Breast Cancer Study.

Chemotherapy is one of the common treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). MDR is caused by the activity of diverse ATP binding cassette (ABC) transporters that pump drugs out of the cells. There are several drugs which have been used in treatment of cancer. One of them is doxorubicin that intercalates and inhibits DNA replication. However, doxorubicin has been found to cause development of MDR in tumors. It has been reported that there is a correlation between multidrug resistance and invasiveness of cancer cells. Vimentin is a type III intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and also poor prognosis of cancer. There are several studies that have shown the connection between expression level of vimentin and invasiveness. In this study, MCF-7 cell line (MCF-7/S), which is a model cell line for human mammary carcinoma, and doxorubicin resistant MCF-7 cell line (MCF-7/Dox) were used. The resistant cell line was previously obtained by stepwise selection in our laboratory. The main purpose of this study was to investigate changes of metastatic behaviour in MCF-7/Dox cell line, after transient silencing of vimentin gene by siRNA. In conclusion, down-regulation of vimentin gene expression in MCF-7/Dox cell lines was expected to change the characteristics in migration and invasiveness shown by migration and invasion assays.

This study aimed at revealing and differentiating the emotions of shame and guilt felt by the adolescents with maternal cancer. In order to reveal and differentiate these emotions, a sentence completion task and interviews were used. The study was conducted on 10 adolescents in age range of 16-20. With each participant, four private sessions were made. In the first session, the participant&rsquo / s knowledge of his/her mother&rsquo / s condition was evaluated through the Sentence Completion Test. In the second session, Pandora&rsquo / s Box, a film by Yesim Ustaoglu was watched with the participant to understand if the film evoked the targeted emotions and the second format of Sentence Completion Test was given. In the third session, 20 minute interviews were conducted with the participant, privately. These interviews were called &ldquo / interventions&rdquo / because they aimed to intervene to the process of feeling guilty and ashamed and replace them with a positive self-conscious emotion, pride. The fourth and final session was conducted after one week and aimed to check if the anticipated affect of film and interventions lasted. Only 3 participants out of 10 returned for the fourth session, so the fourth session was left out of the analysis. Two main analyses were conducted in the current study. The frequencies of shame and guilt were examined in the Sentence Completion Test analysis and the interviews were analysed qualitatively. The outcome resulted that in both Sentence Completion Test and interview analysis, the adolescents with maternal cancer revealed emotions of shame and guilt. Furthermore, in the Sentence Completion Test analysis, it was tested whether the frequency of emotions of shame and guilt increased or decreased by the intervention of the film and interviews and the outcome yielded that neither the film Pandora&rsquo / s Box nor the interventions made any significant effect. The results were evaluated and the implications were discussed. Finally, limitations of the study and recommendations for future research were explained. Keywords: Cancer, breast cancer, adolescents, self-conscious emotions, Cinematherapy, Interventions Technique, Qualitative Study.

This study aimed at revealing and differentiating the emotions of shame and guilt felt by the adolescents with maternal cancer. In order to reveal and differentiate these emotions, a sentence completion task and interviews were used. The study was conducted on 10 adolescents in age range of 16-20. With each participant, four private sessions were made. In the first session, the participant&rsquo / s knowledge of his/her mother&rsquo / s condition was evaluated through the Sentence Completion Test. In the second session, Pandora&rsquo / s Box, a film by Yesim Ustaoglu was watched with the participant to understand if the film evoked the targeted emotions and the second format of Sentence Completion Test was given. In the third session, 20 minute interviews were conducted with the participant, privately. These interviews were called &ldquo / interventions&rdquo / because they aimed to intervene to the process of feeling guilty and ashamed and replace them with a positive self-conscious emotion pride. The fourth and final session was conducted after one week and aimed to check if the anticipated affect of film and interventions lasted. Only 3 participants out of 10 returned for the fourth session, so the fourth session was left out of the analysis. Two main analyses were conducted in the current study. The frequencies of shame and guilt were examined in the Sentence Completion Test analysis and the interviews were analysed qualitatively. The outcome resulted that in both Sentence Completion Test and interview analysis, the adolescents with maternal cancer revealed emotions of shame and guilt. Furthermore, in the Sentence Completion Test analysis, it was tested whether the frequency of emotions of shame and guilt increased or decreased by the intervention of the film and interviews and the outcome yielded that neither the film Pandora&rsquo / s Box nor the interventions made any significant effect. The results were evaluated and the implications were discussed. Finally, limitations of the study and recommendations for future research were explained.