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The role of glycosaminoglycans in the adhesion of tumour cells to endotheliumPrice, Elizabeth Anne January 1995 (has links)
No description available.
Genome wide copy number and gene expression profiling using archived tissue for molecular marker studies in breast cancerIddawela, Mahesh Yasantha Bandara January 2011 (has links)
No description available.
Targeting aerobic glycolysis in breast and ovarian cancerXintaropoulou, Chrysi January 2017 (has links)
Cancer cells, unlike normal tissue, frequently rely on glycolysis for the production of energy and the metabolic intermediates required for their growth regardless of cellular oxygenation levels. This metabolic reconfiguration, termed the Warburg effect, provides a potential strategy to preferentially target tumours from a therapeutic perspective. The present study sought to investigate the glycolytic phenotype of breast and ovarian cancer, and assess the possibility of exploiting several glycolytic targets therapeutically. Initially the growth dependency of breast and ovarian cancer cells on the availability of glucose was established. An array of 10 compounds reported to inhibit key enzymes of the glycolytic pathway were investigated and compared against an extended panel of breast and ovarian cancer cell line models. All inhibitors investigated, targeted against multiple points of the pathway, were shown to block the glycolytic pathway as demonstrated by glucose accumulation in the culture media combined with decreased lactate secretion, and attenuated breast and ovarian cancer cell proliferation in a concentration dependent manner. Furthermore their mechanism of action was investigated by flow cytometric analysis and their antiproliferative effect was associated with induction of apoptosis and G0/G1 cell cycle arrest. The glycolytic inhibitors were further assessed in combination strategies with established chemotherapeutic and targeted agents and several synergistic interactions, characterised by low combination index values, were revealed. Among them, 3PO (a novel PFKFB3 inhibitor) enhanced the effect of cisplatin in both platinum sensitive and platinum resistant ovarian cancer cells suggesting a strategy for treatment of platinum resistant disease. Furthermore robust synergy was identified between IOM-1190 (a novel GLUT1 inhibitor) and metformin, an antidiabetic inhibitor of oxidative phosphorylation, resulting in strong inhibition of breast cancer cell growth. This combination is proposed for the treatment of highly aggressive triple negative breast tumours. An additional objective of this research was to investigate the effect of the oxygen level on sensitivity to glycolysis inhibition. Breast cancer cells were found to be more sensitive to glycolysis inhibition in high oxygen conditions. This enhanced resistance at low oxygen levels was associated with upregulation of the targeted glycolytic enzymes as demonstrated at both the mRNA (by gene expression microarray profiling, Illumina BeadArrays) and protein level (by Western blotting). Manipulation of LDHA (Lactate Dehydrogenase A) by siRNA knockdown provided further evidence that downregulation of this target was sufficient to significantly suppress breast cancer cell proliferation. Finally, the expression of selected glycolytic targets was examined in a clinical tissue microarray set of a large cohort of ovarian tumours using quantitative immunofluorescence technology, AQUA. The role of the glycolytic phenotype in ovarian cancer was suggested and interesting associations between the glycolytic profile and clear cell and endometrioid ovarian cancers revealed. Increased PKM2 (Pyruvate kinase isozyme M2) and LDHA expression were demonstrated in clear cell tumours and also low expression of these enzymes was significantly correlated with improved survival of endometrioid ovarian cancer patients. Taken together the findings of this study support the glycolytic pathway as a legitimate target for further investigation in breast and ovarian cancer treatment.
Combining regulatory angiogenic gene therapy and virotherapy for the treatment of breast cancerBazan Peregrino, Miriam January 2007 (has links)
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.
Investigating the functional significance of an FGFR2 intronic SNP in breast cancerRobbez-Masson, Luisa January 2013 (has links)
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.
Advanced Raman techniques for real time cancer diagnosticsVardaki, Martha January 2016 (has links)
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.
Porovnání účinnosti vybraných metod léčení rakoviny prostaty a prsu pomocí analýzy přežití / Comparing the effectiveness of selected methods of cancer treatment. Prostate cancer, breast cancer and lung cancer via survival analysisŠimonková, Karolína January 2017 (has links)
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.
Metastatic Behaviour Of Doxorubicin Resistant Mcf-7 Breast Cancer Cells After Vimentin SilencingTezcan, Okan 01 January 2013 (has links) (PDF)
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.
The Differentiation Of Emotions Of Shame And Guilt In Adolescents With Maternal Breast CancerKacmaz, Belgu Lale 01 September 2011 (has links) (PDF)
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.
The Differentiation Of Emotions Of Shame And Guilt In Adolescents With Maternal Breast CancerKacmaz, Lale Belgu 01 September 2011 (has links) (PDF)
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.
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