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1
Tran, Vanessa Hoang Medical Sciences Faculty of Medicine UNSW. "Breath biomarkers associated with lung cancer." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43717.
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Lung cancer (LC) is often diagnosed at advanced stage and as a result, survival rates are low. Recent studies describe exhaled breath and exhaled breath condensate (EBC) as a potential non-invasive method of sampling the airways for assessing inflammation of the respiratory system, and possibly for the early detection of LC. It was hypothesised that higher concentrations of markers and protein will be present in the EBC of LC patients compared to those of normal controls and healthy smokers, and may aid in assessing lung status. Methods: The gaseous phase of breath was investigated for volatile organic compound (VOC) patterns using an electronic nose (eNose) system, in addition to off-line measurements of carbon monoxide (CO) and nitric oxide (NO) levels. The aqueous phase, EBC, was collected during tidal breathing through a glass collection device cooled to 4??C by ice. Nitrite/nitrate (NOx) and pH levels were determined by a fluorescent modification of the Griess method, and silicon chip sensor pH meter, respectively. Protein levels in EBC were examined with a bicinchoninic acid (BCA) assay, silver staining and PAGE techniques, while the levels of tumour markers, CYFRA 21-1 and CEA, were quantified by enzyme-linked immunosorbent assays (ELISA). Results: The eNose machine was not able to produce characteristic VOC profiles from exhaled breath unique to each study group, while no significant difference was observed for mean NOx concentrations in the LC group when compared to other subjects (p=0.8824). Higher protein levels were found in the EBC of LC patient compared to normal controls (p=0.0204), with subsequent measurements of elevated CEA levels observed in the LC group when compared to non-smokers and smokers (p=0.023). Conclusion: This study showed that protein can be detected in the exhaled breath condensate of patients, with a significantly elevated amount in the samples from newly diagnosed LC patients. The mechanism for these differences remains to be determined but may be related to inflammatory changes within the airway, such as vascular protein leakage and release of mediators. Future work may aim to identify the upregulated proteins, and focus on proteomics and tissue microarrays to explore candidate proteins.
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Thekedar, Bhushan. "Investigations on the use of breath gas analysis with Proton Transfer Reaction Mass Spectrometry (PTR-MS) for a non-invasive method of early lung cancer detection." kostenfrei, 2009. https://mediatum2.ub.tum.de/node?id=821780.
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Grabner, Enrico. "Untersuchung von Promotormethylierungen des p16-Gens im Atemkondensat von Patienten mit Bronchialkarzinom und Vergleich mit Tumorpräparaten." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-158654.
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Angesichts der nach wie vor hohen Mortalität und Morbidität des Bronchialkarzinoms ist die Entwicklung geeigneter Methoden zur früheren Diagnostik eine wichtige Notwendigkeit, um die geringe durchschnittliche 5-Jahres-Überlebensrate von 15% – 18% zu steigern.
Unter diesem Gesichtspunkt wurde in der vorliegenden Arbeit das Atemkondensat von Patienten mit Bronchialkarzinom als nicht-invasiv und kostengünstig zu gewinnendes Medium auf das Vorliegen eines potentiellen Screeningmarkers – dem methylierten Tumorsuppressor-Gen p16 – untersucht.
Dazu wurde ein Versuchsablauf entwickelt, bei dem trotz des geringen DNA-Gehaltes im Atemkondensat p16-Methylierungen nachgewiesen werden konnten. Die letztendlich etablierte Methode war eine methylierungsspezifische nested-PCR mit anschließendem Restriktionsverdau durch das Restriktionsenzym BstUI. Des Weiteren erfolgte die Untersuchung von in Paraffin eingebetteten Tumorpräparaten der Patienten.
In der anschließenden statistischen Auswertung wurde der Einfluss von verschiedenen Faktoren wie COPD-Grad, Tumorlage, Tumorart, Nikotinabusus und stattgehabte Chemo- oder Strahlentherapie auf den Methylierungsstatus des p16-Gens analysiert.
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Soerjomataram, Isabelle. "Multiple primary cancers in patients with breast ans skin cancer." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10779.
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Habes, Chahrazed. "Stimulation du signal calcique et de la migration des cellules cancéreuses mammaires par le peptide LL-37 : un mécanisme d’attachement membranaire impliquant les glycosaminoglycanes et les syndécanes." Thesis, Tours, 2019. http://www.theses.fr/2019TOUR3807.
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Le peptide LL-37, peptide antimicrobien de l’immunité innée, est associé au développement tumoral. Sur des lignées cancéreuses mammaires. Il augmente le calcium intracellulaire et la migration. via l’activation de la voie PI3K/AKT et de canaux calciques. L’énantiomère (D)-LL-37 induit des effets similaires, excluant une interaction classique ligand-récepteur. Avec sa structure en hélice α amphipathique et sa charge nette +6, l’hypothèse était que le peptide utilise les charges négatives de glycanes sulfatés ou sialylés pour sa fixation membranaire avant d’induire ses activités. Des lectines végétales reconnaissant des structures glycaniques sialylées ou sulfatées inhibent la migration et le signal calcique induits par LL-37 mais l’implication de sialyltransférases n’a pas été démontrée. Des glycoaminoglycanes (GAGs) tels que les chondroïtine et héparine sulfatées, utilisés en tant que compétiteurs, ou une digestion enzymatique des GAGs (Chondroïtinase et héparinase) conduisent à une inhibition de 50 à 100% des activités migratoire et calcique induites par LL-37. L’inhibition de synthèse des GAGs par le Methylumbelliferyl β-D-xyloside ainsi qu’une diminution de la sulfatation par le chlorate de sodium confirment l’implication de ces glycanes sulfatés. Dans la perceptive d’identifier la ou les protéines glycosylées membranaires susceptibles de transduire les effets de LL-37, nous avons utilisé une approche ciblée en invalidant par siRNA la synthèse des protéines arborant des GAGs. Le syndécane 4 est impliqué dans les activités de LL-37. En conclusion, ces résultats soulignent l’implication de GAGs sulfatés portés par le syndécane 4 pour orienter la fixation de LL-37 à la membrane des cellules cancéreuses et médier ses activités pro-tumoralesInitially characterized by its antimicrobial activities, LL-37 has also been shown to significantly contribute to tumor development. On breast cancer cell lines, LL-37 increases intracellular calcium and their migration via the activation of PI3K/AKT signaling. Its all-D enantiomer (D)-LL-37 induces similar effects, which excludes an protein-protein interaction of LL-37 in a classic ligand-receptor manner. Its structure of an amphipathic a-helix with a net charge of +6 gave rise to the hypothesis that the peptide uses the negative charges of sulfoglycans or sialic acids to facilitate its attachment to the cell membrane and to induce its activities. Whereas several lectins, specifically attaching to sialylated or sulfated structures, blocked the activities of LL-37 on both calcium increase and cell migration, the suppression of several sialyltransferases had no effect. However, the competitive use of glycoaminoglycans (GAG) and chrondroitin and sulfated heparin, or treatment of the cell surface with chondroitinase and heparinase resulted in an activity loss of 50-100%. Similar results were obtained by confirmed by blocking the synthesis of GAGs with Methylumbelliferyl β-D-xyloside, and by suppression of glycan sulfurylation by sodium chlorate. Using a candidate approach by suppressing proteoglycan synthesis by RNA interference, syndecan 4 was shown to be involved in the activities of LL-37. This leads to the conclusion that sulfated GAGs linked to syndecans 4 guides the association of LL-37 to the membrane of cancer cells, thus being a mediator of its activities
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Irobi, Edward Okezie. "Time to Diagnosis of Second Primary Cancers among Patients with Breast Cancer." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2661.
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Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan-Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, 95% CI [1.03 - 2.11], White = 1.511, 95% CI [1.18 - 1.94], and American Indian/Hawaiian = 1.424, 95% CI [1.12 -1.81] showing positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.
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Vehmanen, Paula. "Breast cancer-predisposing genes in Finnish breast and ovarian cancer families." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/vehmanen/.
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Clark, Jacqueline. "Living with Breast Cancer: Emotion-Work Strategies in Breast Cancer Support Groups." NCSU, 2007. http://www.lib.ncsu.edu/theses/available/etd-03122007-104945/.
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Research on stress and coping has attempted to explain how people deal with difficult life events, such as the diagnosis of a potentially life-threatening disease. Little attention, however, has been given to how people work together to cope with and manage the emotions evoked by such events. The present study looks at women who joined four breast cancer support groups to help them cope with the emotional fallout of the disease. Data from participant observation in these four groups, in addition to 35 in-depth interviews, are used to develop an analysis of how the women learned to cope collectively with their disease. Seven emotion-work strategies are identified and discussed, including: (a) seeking information; (b) concealing illness; (c) engaging in sexualized joking; (d) practicing compensatory femininity; (e) creating and sharing medicalized stories; (f) taking on the identity of breast cancer survivor; and (g) redefining illness as a blessing. The analysis shows how these strategies were influenced by the class-based resources the women brought with them to the groups. It also illustrates how these strategies (and thus the women?s coping efforts) were influenced and constrained by the mainstream breast cancer culture.
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Pelon, Floriane. "Fibroblastic heterogeneity and metastatic spread in breast cancers Fibroblast heterogeneity drives metastatic spread in breast cancer through distinct mechanisms." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2392&f=17330.
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Les cancers du sein, premiers cancers féminins et causes aujourd’hui encore de nombreux décès, sont classés en 3 sous-types moléculaires : luminaux –les plus répandus, HER2 et triple-négatifs (TN) –les plus agressifs. Lors du diagnostic, l’envahissement des ganglions lymphatiques axillaires par les cellules tumorales est établi. Il s’agit, en plus de la classification moléculaire, d’un marqueur pronostique utilisé en clinique pour stratifier les patientes, car il informe sur le risque de développement ultérieur de métastases, cause majeure des décès à l’heure actuelle. Les tumeurs solides, et notamment les cancers du sein, sont des écosystèmes complexes comprenant de nombreux types cellulaires qui interagissent avec les cellules cancéreuses. Parmi eux, les fibroblastes associés au cancer (CAF) sont les plus abondants et participent activement à de nombreux aspects de la tumorigenèse dont la croissance, l’invasion, l’angiogenèse, l’immunosuppression. Cependant, ils constituent une population hétérogène et à ce jour, très peu d’études ont analysé cette hétérogénéité tout en la liant aux diverses fonctions décrites des CAF. Dans ce projet, nous nous sommes intéressés au rôle de cette hétérogénéité fibroblastique dans la dissémination métastatique des cancers du sein. En combinant l’étude de plusieurs marqueurs de CAF, nous avons montré que les ganglions lymphatiques envahis par les cellules tumorales sont constitués de 4 sous-populations de CAF (CAF-S1, S2, S3 et S4), similaires à celles identifiées dans les tumeurs primaires appariées. De façon intéressante, ce sont les deux sous-types de CAF myofibroblastiques (αSMA+), CAF-S1 et particulièrement CAF-S4, qui s’accumulent préférentiellement dans les ganglions métastatiques. Ils présentent les mêmes signatures transcriptomiques entre les deux localisations tissulaires (ganglions envahis et tumeurs primaires correspondantes). Or, ces deux populations CAF-S1 et CAF-S4 augmentent le phénotype invasif des cellules tumorales, en régulant des fonctions complémentaires. D’un côté, les CAF-S1 sont hautement motiles, et stimulent la prolifération, la migration, l’invasion et l’initiation d’une transition épithélio-mésenchymateuse des cellules de cancer du sein. De l’autre, les CAF-S4 sont très contractiles, capables de remodeler la matrice extracellulaire et promeuvent ainsi l’invasion et la motilité des cellules tumorales dans des systèmes en 3 dimensions. Des expériences fonctionnelles suggèrent que l’action des CAF-S1 implique CXCL12 et TGFβ tandis que celle des CAF-S4 dépend de la voie NOTCH. En accord avec ces résultats, l’accumulation des CAF et leur identité dans les ganglions envahis constituent deux nouveaux facteurs pronostics dans les cancers du sein, indépendants du sous-type de cancers du sein et de l’envahissement ganglionnaire. En effet, un fort contenu en CAF-S4 y est associé avec un développement ultérieur de métastases à longue distance. Ainsi, analyser le contenu fibroblastique des ganglions axillaires au diagnostic pourrait constituer une information nouvelle et utile à la prise en charge des patientesBreast cancers are the most common cancers in women and despite great improvements in treatments, they are still responsible for many deaths worldwide. They are classified into 3 main molecular subtypes: Luminal cancers are the most frequent ones, while HER2 and TN are the most aggressive. At diagnostic, lymph node involvement is also assessed as it constitutes, in addition to molecular classification, a strong prognostic marker. Indeed, it informs on the risk to develop further distant metastases, which is the main cause of death by cancer. Solid tumors, including breast cancers, are complex ecologies comprising numerous different cell types that interact with cancer cells. Among them, cancer-associated-fibroblasts (CAF) are the most abundant and actively participate in many tumor hallmarks such as tumor growth, invasion, immunosuppression and angiogenesis. However, they do not constitute a homogeneous population but so far, only few studies have characterized this heterogeneity and linked it to CAF previously described functions. In this project, we focused on the potential involvement of CAF heterogeneity in breast cancer metastatic spread. Combining the analysis of several CAF markers, we showed that invaded LN comprise 4 CAF subsets (CAF-S1, S2, S3 and S4), similar to those found in primary tumors. Interestingly, the two myofibroblastic subsets (αSMA+) CAF-S1 and especially CAF-S4 preferentially accumulate in metastatic LN and present the same transcriptomic profiles in both tumors and LN. Importantly, both CAF-S1 and CAF-S4 display pro-invasive properties, by acting at different levels on tumor cells. On the one hand, highly motile CAF-S1 stimulate breast cancer cell proliferation, migration and EMT initiation. On the other hand, CAF-S4 exhibit an important contractility and by remodeling the matrix they are able to promote tumor cell invasion in 3D. Functional studies highlight a CXCL12/TGFβ involvement in CAF-S1 functions while CAF-S4 pro-invasive phenotype appears to be Notch-dependent. In agreement with these data, we found that CAF accumulation and subset enrichment in involved LN were two new prognostic factors, independent of breast cancer molecular subtypes and LN status at diagnosis. Indeed, stromal rich LN with a predominance of CAF-S4 are associated with long distance metastases development and poor overall survival. Thus, we propose that analyzing LN fibroblastic content at diagnosis could constitute new and useful information to breast cancer patients’ care
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Cheok, Frida. "Participation in mammographic screenings in South Australia /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phc51843.pdf.
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Villman, Kenneth. "Chemosensitivity in Breast Cancer." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : [Univ.-bibl. [distributör]], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7459.
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Haen, Roel. "Breast cancer related lymphedema." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:c4a83ffc-790f-46ec-bde2-3ac639dd7c89.
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Improvements in the treatment of breast cancer have resulted in better survival rates and less breast cancer related morbidity. Nevertheless, a significant group of patients still experience a diminished quality of life as a result of lymphedema. In the early, often reversible, stage of lymphedema patients can experience subjective changes in the affected area. However, with the traditionally available tools the lymphedema often remains clinically undetectable and patients are denied essential care that can prevent worsening. Furthermore, most lymphedema assessment tools fail to support a clear unambiguous definition of lymphedema. This underlines the need for a sensitive objective measurement method that can assess lymphedema in a subclinical stage. In this study we demonstrated that measuring tissue dielectric constant (TDC) using the MoistureMeter-D is an effective method to detect tissue water changes and could potentially provide a cost-effective adequate tool to measure the early onset of breast cancer related lymphedema (BCRL). Secondarily, we established the correlation between the novel TDC method and the frequently used arm volume measurements and self-assessment questionnaires. A group of 20 female patients with clinically BCRL were included. TDC measurements in both arms and all quadrant of both breast were recorded along with volumetric measurements of both arms. All patients were asked to complete a self-report questionnaire. The novel TDC method detected significantly higher tissue water levels in the affected arm and breast compared to the control side. The TDC ratio between control and affected side showed significant correlation with self-reported pain and discomfort in both arm and breast. In the arm, the TDC method also showed correlation with the volume measurement method. The TDC value of the arm was correlated to age, but not to BMI. This study demonstrates that measuring TDC using the MMD is an effective method for quantifying lymphedema in arm and breast and is an important tool in detecting early TWC changes.
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Bakir, Ayse. "Aluminium and breast cancer." Thesis, University of Reading, 2017. http://centaur.reading.ac.uk/72586/.
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Al-based antiperspirant salts have been implicated as a causative factor in the development of breast cancer due to their proximity of application to the upper outer quadrant of the breast where the majority of breast cancers originate. Since mortality results from metastasis of breast cancer, this thesis has investigated the effects of Al chloride and Al chlorohydrate at 10-4M and 10-5M concentrations on the migratory and invasive abilities of four human breast cell lines. 10-5M was chosen as the concentration of Al previously measured in human nipple aspirate fluids. Effects on migration and invasion of MCF-7, MDA-MB-231, MCF-12A and HMF-3A human breast cells were explored using time-lapse microscopy, wound-healing assays and xCELLigence technology. Molecular pathways involving MMP-9, MMP-2, MMP-14, TIMP-1, TIMP-2, TIMP-3, ferritin and NDRG-1 were studied using RT-PCR, western immunoblotting and gelatin zymography. Prior exposure to Al increased the motility of MCF-7 cells after 32 weeks, of MDA-MB-231 cells after 25 weeks of prior exposure and of MCF-12A cells after 11 weeks. At a molecular level, Al chloride and Al chlorohydrate at 10 -5 M and 10 -4 M concentrations affected MMP-9 and MMP-14 mRNA and protein levels in MCF-7, MDA-MB-231 and MCF-12A cells. Although Al did not alter the motility of HMF-3A cells, changes in MMP-9, MMP-2 and MMP-14 mRNA expression and MMP-14 protein levels were found. Levels of the MMP inhibitors, TIMP 1, 2, and 3 were altered in MDA- MB-231 cells. Changes were observed in TIMP-3 levels in MCF-12A cells and TIMP-2 expression in HMF-3A cells. In considering the effects of Al on iron homeostasis, Al chloride was found to enhance ferritin levels in MCF-7 cells after 27weeks and in MCF-12A cells after 1week. Al chlorohydrate increased ferritin levels in MDAMB-231 cells after 21weeks. NDRG-1 mRNA and protein levels in MCF-7, MDA-MB-231 and MCF-12A cells were also affected but only NDRG-1 mRNA was altered in HMF-3A cells. Overall, it can be concluded that Al salts increase migration and invasion of human breast epithelial cells irrespective of whether they are transformed (MCF-7, MDA-MB-231cells) or not (MCF-12A cells), and irrespective of whether the cancer cells are oestrogen responsive (MCF-7 cells) or not (MDA-MB-231 cells). The changes observed in the levels of MMP-2, MMP-9 and MMP-14 and their inhibitors are indicative of a potential molecular pathway. The results demonstrate that exposure to Al chloride can increase ferritin levels, implicating alteration to iron homeostasis which is a known factor in the development of breast cancer. The results also showed that NDRG-1 expression, whose increase may depend on cell stress as for nickel, may not cause alterations observed in migration and invasion. In the light of these findings, it can be concluded that Al has mechanistic potential to cause metastatic tumour spread, which is the major reason for breast cancer mortality.
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Zeidan, Bashar. "Breast cancer biomarker discovery." Thesis, University of Southampton, 2013. https://eprints.soton.ac.uk/360029/.
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Several environmental and genetic factors are involved in breast cancer development and prognosis. It is clear that mortality rate of breast and other cancers increase with advanced clinical and pathological stage. Early detection thus holds the best cure and identification of prospective markers for breast cancer early detection, as well as understanding the mechanisms of its tumourigenesis and metastatic spread are prerequisites for more effective disease management. This report describes our investigations in breast cancer biomarkers discovery. Here, serum samples from healthy volunteers and patients with breast tumours were analysed and compared to reveal diagnostic and prognostic breast cancer biomarkers. Biobanks hold a large number of samples that could provide statistically powerful cohorts with a wealth of lengthy follow up data; useful for pre disease / treatment biomarker discovery. However, ambiguous handling standards and source variability have limited their analysis. Conducting a two centre study, we illustrated that archival serum samples can be reliably analysed with high reproducibility. This highlights the utility of such samples for validation of markers discovered in recent studies. In addition, these samples could select for "real world" biologically stable marker entities. This work suggested that this is a potentially useful proteomic arena; however the corner stone for any future archival discovery projects remains dependent on multi centre immunovalidation. Breast cancer biomarkers including ER/PR and HER2 status; have led to targeted patient stratification and therapy. A more complex molecular sub classification could explain the different outcome within the disease sub groups. However, clinically reliable early detection and markers remain missing . Here, we investigated differentially expressed serum markers between non metastatic breast cancer, benign breast disease and healthy volunteers. Three validated candidate biomarkers (ANX A3, Apo Cl and a 6.4kDa biomarker) differentiating the three groups. Such breast cancer markers can be used as adjuncts to mammography. Further validation of these markers is ongoing and will be followed by elucidation of potential related molecular pathways. Finally, using a novel proteomic profiling platform, we identified and validated three prediction markers of post treatment outcome in early onset breast cancer. Here, ANX A2, Apo Cl and NOS2 were confirmed as serum prognosticators, and further validation and elucidation of their biological role in the disease holds promise for improved and personalised treatment regimes.
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Irwin, Gareth William. "BRCAness in breast cancer." Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706986.
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Background - Breast cancer can be defined various techniques such as immunohistochemistry, gene expression profiles and the presence of genetic mutations. One of these subgroups possesses a sensitivity to DNA-damaging chemotherapy, the BRCAness phenotype. It remains difficult to define this subgroup prior to treatment. This project aims to define BRCAness in breast cancer by assessing BRCAness using three methods: microarray profiling, immunohistochemistry and genetic mutations. Results - A 44 gene signature to predict DNA Damage Repair Deficient Breast cancers was developed from a training cohort of FFPE derived breast tumours enriched for BRCA1/2 mutant cancers. This signature was retrospectively applied to a cohort of sporadic breast cancers and subsequently validated as predictive for improved outcome in a cohort of early-stage breast cancers treated with anthracycline-based chemotherapy, a group that exhibits BRCAness. BRCA1 expression was measured by immunohistochemistry, however, this approach failed to predict benefit from chemotherapy in this study. Finally, a mutation, identified in SF3B1, plays a significant role in the DNA damage response and that absence or mutation of SF3B1 leads to sensitivity to DNA damage and this may be a predictor of BRCAness. Conclusion - In summary, we have shown that BRCAness is best defined by gene array profiling. We have shown that BRCA1 immunohistochemistry is of limited use for predicting patient outcomes in breast cancer. Finally, we identified of specific mutations within SF3B1 that induce sensitivity to DNA damage based chemotherapy.
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Jiao, Xiang. "Somatic Mutations in Breast Cancer Genomes : Discovery and Validation of Breast Cancer Genes." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-182319.
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Breast cancer is the most common cancer in women worldwide. However, the genetic alterations that lead to breast cancer are not fully understood. This thesis aims to identify novel genes of potential mechanistic, diagnostic or therapeutic interest in breast cancers by mutational analysis and whole-genome sequencing. In paper I, sequencing of 36 previously identified candidate genes in 96 breast tumors with patient-matched normal DNA determined the somatic mutation prevalence of these candidate genes and identified additional mutations in Notch, NF-κB, PI3K, and Hedgehog pathways as well as in processes mediating DNA methylation, RNA processing and calcium signaling. In paper II, comparison of massively parallel mate-pair sequencing results of a human genome before and after phi29-mediated multiple displacement amplification (MDA) revealed that MDA introduces structural alteration artifacts, with an emphasis on false positive inversions, and impairs the sensitivity to detect true inversions. Therefore, MDA has limited value in sample preparation for whole-genome sequencing for structural alteration detection. In paper III, massively parallel paired-end sequencing identified gene rearrangements in 15 hormone receptor negative breast cancers. Forty validated rearrangements were predicted to directly affect 30 genes, involved in epigenetic regulation, cell mitosis, signalling transduction and glycolytic flux. RNA interference-based assays revealed the potential roles in cell growth of some affected genes, among which DDX10 was implicated to be involved in apoptosis. In paper IV, a method for statistical evaluation of putative translocations detected by massively parallel paired-end sequencing was proposed. In an application of this method to analyse translocations detected by cancer genome deep paired-end sequencing, 76 putative translocations were classified into four categories, with the majority likely to be caused by mismapping due to repetitive regions. Taken together, this thesis provides insights into genes and pathways mutated in sporadic breast cancer genomes, which broaden our understanding of the genetic basis of breast cancer and may ultimately facilitate the diagnosis and treatment of this disease.
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Chen, Hsiu-Hsi. "Mathematical models for progression of breast cancer and evaluation of breast cancer screening." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388263.
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Sterrenberg, Jason Neville. "Molecular chaperone expression and function in breast cancer and breast cancer stem cells." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1016238.
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The Cancer Stem Cell (CSC) theory suggests that cancers arise from and are maintained by a subpopulation of cancer cells with stem cell properties. Molecular chaperones are key components of cellular regulation. The overexpression of chaperones has become synonymous with cancer cells with chaperones being recognized as bona fide anti-cancer drug targets. Although chaperone activity has been characterized in cancer cells, very little is known about the cellular functions of chaperones in cancer stem cells. We set out to compare the expression of selected molecular chaperones in non-stem cancer cell and cancer stem cell enriched populations isolated from breast cancer lines, in order to identify chaperones differentially expressed between the two populations for further biological characterization. In order to isolate breast cancer stem cells from the MCF-7 and MDA-MB-231 breast cancer cell lines, three cancer stem cell isolation and identification techniques were utilized based on (1) cell surface marker expression (CD44+/CD24- and CD44+/CD24-/EpCAM+ phenotypes), (2) aldehyde dehydrogenase enzyme activity (ALDHHi) and (3) ability to grow in anchorage-independent conditions. The MDA-MB-231 and MCF-7 breast cancer cell lines displayed CD44+/CD24- cell populations with the MCF-7 cell line additionally displaying a large CD44+/CD24-/EpCAM+ population. Although both cell lines showed similar ALDHHi populations, they differed substantially with respect to anchorage-independent growth. MCF-7 cells were able to form anchorage-independent colonies while the MDA-MB-231 cell line was not. Anchorage-independent MCF-7 cells showed enrichment in CD44+/CD24- and CD44+/CD24-/EpCAM+ cells compared to adherent MCF-7 cells, and were selected for gene expression studies. Gene expression studies identified 22 genes as being down-regulated at the mRNA level in the anchorage-independent MCF-7 cells, while only 2 genes (BAG1 and DNAJC12) were up-regulated. The down-regulation of selected chaperones in anchorage independent MCF-7 cells was confirmed at the protein level for selected chaperones, including DNAJB6, a type II DNAJ protein shown to be involved in the regulation of Wnt signaling. In order to characterize the effect of DNAJB6 expression on BCSCs we developed a pCMV mammalian expression plasmid for both DNAJB6 isoforms (DNAJB6L and DNAJB6S). We successfully constructed mutants of the conserved histidine-proline-aspartic acid (HPD) motif of the J domain of DNAJB6S and DNAJB6L. These constructs will allow the analysis of the role of DNAJB6 in cancer stem cell function. To the best of our knowledge, this is the first report to focus on the comparative expression of molecular chaperones in normal and cancer stem cell enriched breast cancer populations.
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Douglass, Christine. "Collaborative visual ethnography and breast cancer." Thesis, University of Westminster, 2015. https://westminsterresearch.westminster.ac.uk/item/9qx13/collaborative-visual-ethnography-and-breast-cancer.
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The aim of this cross-disciplinary, practice-based PhD was to develop, justify and implement an ethical, collaborative visual research methodology to explore and make visible individual experiences of breast cancer. Nine women, from different ethnic backgrounds, diagnosed with breast cancer nine-36 months before commencement of the study were given video cameras and invited to film their lives. They filmed for an average of nine months and three weeks. The practice component of this research comprised nine individual films. Together with a ten-minute single screen compilation, projected diary extracts and notes from the participants, they formed a gallery exhibition, What if? The work has progressed existing debates and practices in shared visual ethnography and cross-disciplinary visual research. It provides an original contribution to knowledge through the development of a methodology that has: challenged the reliance on the interview and prior identification of themes as research interventions; offered new insights into reflexive theorising and positioning of investigators in research relationships; countered homogenising, reductive narrative frameworks; and contested fixed models of consent. It also adds to the literature and practices exploring alternative platforms for exhibiting polyphonic, durational visual ethnographic material and to discussions on filmmaking as a therapeutic intervention. In investigations into the lives of others diagnosed with illness, the irreducibility of experience, the multiple truths that co-exist, and the impossibility of investigators becoming similarly situated, demand a respectful, unexploitative, collaborative research methodology. This research proposed an approach that meets these aims.
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Dasch, Kimberly B. "Affective differentiation in breast cancer patients." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 70 p, 2009. http://proquest.umi.com/pqdweb?did=1885670961&sid=7&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Walker, Meagan. "Assessment of Cancer-Related Fatigue in Breast Cancer Survivors." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7348.
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Cancer-related fatigue (CRF) is a persistent and debilitating problem for many breast cancer survivors. Although many CRF measurement tools are available, no consensus exists on the most appropriate tool to use for breast cancer survivors. The purpose of this project was to identify the best method of assessing CRF in breast cancer survivors. The practice-focused question inquired about the most appropriate way to assess fatigue in breast cancer survivors. The central concepts of the project were CRF and cancer survivorship. This project was informed by the theory of health as expanding consciousness and Mishel's theory of uncertainty in illness. The sources of evidence included multi-database searches and literature from professional organizations. Results were tracked using preferred reporting items for systematic reviews and metasystems and a literature review matrix. The search identified 14 sources, which were assessed for quality using the grading of recommendations, assessment, development, and evaluation process. The results of this systematic review did not support the use of any particular assessment tool; however, 2 clinical practice guidelines recommended screening using a numerical severity scale followed by detailed assessment of clinically significant fatigue using available assessment tools. Screening can be implemented into the survivorship clinic, allowing nurses to identify potentially clinically significant fatigue so that further workup is done and interventions are implemented. Identifying, assessing, and intervening for clinically significant fatigue can improve the quality of life for breast cancer survivors, contributing to positive social change.
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Pieters, Huibrie. "From 'Cancer Patient' to 'Cancer Survivor' oldest breast cancer survivors in transition /." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=2023818721&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Želvienė, Aušra. "Women beliefs towards breast cancer, breast self-examination and mammography in connection with participation in breast cancer screening." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2008. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2008~D_20080129_121108-78281.
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The aim of the study is to assess the connection between women’s participation in breast cancer screening and beliefs towards breast cancer, breast self-examination and mammography.
The objectives of the study:
1. To assess validity and reliability of Champion Health Belief Model Scale for beliefs towards breast cancer, breast self-examination and mammography screening for Lithuanian women.
2. To estimate perceived susceptibility, perceived severity, perceived benefits, perceived barriers, confidence and health motivation.
3. To compare beliefs towards breast cancer, breast self-examination and mammography screening of participant and non-participant women in the screening program.
4. To assess perceived barriers towards mammography screening.
5. To investigate the role of information about breast cancer and mammography screening for women‘s beliefs towards breast cancer, breast self-examination and mammography screening.
CONCLUSIONS
1. Champion Health Belief Model Scale is a valid and reliable to assess beliefs towards breast cancer, breast self- examination and mammography. The barriers- mammography item “Regular mammography screening would make me worry about breast cancer” was inappropriate to the scale and expunged from the questionnaire.
2. Surveyed women did not feel much threat to get breast cancer. They overvalued benefits of breast self-examination and positively rated mammography screening. However, confidence to perform breast self-examination was properly low... [to full text]Šio darbo tikslas buvo įvertinti atvykusių ir neatvykusių tikrintis mamografiškai moterų nuostatų į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą skirtumus. Tikslui pasiekti iškelti tokie uždaviniai: 1. Įvertinti Champion VL sveikatos įsitikinimų modelio klausimyno tinkamumą tirti Lietuvos moterų nuostatoms į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą. 2. Nustatyti moterų suvoktą krūties vėžio grėsmę, apsaugančios nuo krūties vėžio pasekmių elgsenos naudą ir kliūtis šiai veiklai, sveikos gyvensenos motyvaciją. 3. Palyginti atvykusių ir neatvykusių tirtis mamografiškai dėl krūties vėžio moterų nuostatas į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą. 4. Įvertinti dalyvavusių atrankinėje mamografinėje patikroje dėl krūties vėžio moterų kliūtis tirtis mamografiškai. 5. Ištirti papildomos informacijos apie krūties vėžį, mamografinę patikrą įtaką moterų nuostatoms į krūties vėžį, savityrą bei atrankinę mamografinę patikrą ir moterų dalyvavimui atrankinės patikros programoje. Išvados: 1. Patikrintas ir įteisintas VL Champion sveikatos įsitikinimų modelio skalės klausimynas yra tinkamas Lietuvos moterų nuostatoms į krūties vėžį, krūtų savityrą ir atrankinę mamografinę patikrą tirti. Sveikos gyvensenos motyvacijos skalė turi būti padalinta į požiūrio į sveiką gyvenseną ir veiklos sveikatos labui subskales. Kliūčių tirtis mamografiškai teiginys “reguliarus mamografinis ištyrimas verstų mane nerimauti dėl krūties vėžio” išbrauktas... [toliau žr. visą tekstą]
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Casellas-Grau, Anna. "Positive psychology in breast cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/392691.
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RESUM
La present tesi doctoral té l’objectiu d’explorar la relació entre la nova branca de la psicologia anomenada psicologia positiva i l’experiència de passar per un càncer de mama. Aquesta relació és estudiada tan des d’un punt de vista teòric com pràctic. Així, des del punt de vista teòric, proporciona informació sobre quins constructes de la psicologia positiva han estat trobats com a estar significativament relacionats amb viure un càncer de mama. També s’estudia quines variables sociodemogràfiques, mèdiques i psicosocials fomenten l’aparició d’aquestes respostes positives en aquest tipus de població. Aquestes dues àrees teòriques van ser explorades a partir de la metodologia de la revisió sistemàtica, i els resultats van mostrar que les respostes més estudiades i relacionades amb el càncer de mama són el creixement posttraumàtic, el benestar, el sentit i la troballa de beneficis. A més, aquelles dones que tenen unes característiques sociodemogràfiques i mèdiques relacionades amb una percepció més estressant de la malaltia (com, per exemple, menor edat o tractaments més agressius) tendeixen a desenvolupar és respostes positives. D’altra banda, també es va trobar com a rellevant el paper de reducció de l’estrès de variables psicosocials com el suport social o les creences religioses, derivant en majors nivells de funcionament psicològic positiu en les dones.
Pel què fa al punt de vista pràctic, es van explorar aquelles intervencions derivades de la psicologia positiva que havien estat aplicades en dones amb càncer de pit. La metodologia emprada va ser, també, la revisió sistemàtica, i els resultats mostraren que hi ha poques teràpies de la psicologia positiva aplicades en aquest tipus de població, i que aquestes teràpies són heterogènies. Es van distingir cinc grups d’intervencions: intervencions basades en el mindfulness, teràpies promotores del sentit, teràpies psicoespirituals, intervencions basades en l’escriptura d’emocions positives i una teràpia per promoure l’esperança. Donada l’escassetat trobada, es va considerar necessària l’avaluació empírica de l’eficàcia d’una psicoteràpia positiva per a supervivents de càncer amb alts nivells de malestar. Els objectius de la teràpia eren la reducció de símptomes d’estrès a partir de l’augment del creixement posttraumàtic. Els resultats, efectivament, van mostrar que la teràpia complia els seus objectius. En relació al creixement posttraumàtic, també és discutida la seva autenticitat, abordant les dades empíriques en relació a la corroboració per part dels familiars del creixement posttraumàtic dels supervivents de càncer. Realment, els familiars dels supervivents van corroborar el creixement posttraumàtic reportat per aquests.This thesis is aimed at the study of the relationship between the new branch named positive psychology and the experience of undergoing a breast cancer. It is studied from a theoretical, but also a practical perspective. Therefore, from a theoretical point of view, it provides data about which constructs of positive psychology have been studied and found among women who had been diagnosed with breast cancer. Also, it is explored which sociodemographical, medical and psychosocial variables can promote the emergence of these positive responses among the cited population. These two areas were studied using the systematic review methodology, and results showed that the most studied and found positive responses from the experience of undergoing a breast cancer are posttraumatic growth, well-being, benefit finding and meaning. In addition, those women who had sociodemographical and medical characteristics related with a higher stressful perception of their illness (e.g. younger age, more aggressive treatments) tent to later develop more positive responses. The stress-absorbing role of psychosocial variables like social support and having religious beliefs was also explored and found to be relevant in the latter women’s positive psychological functioning. In regards to the practical point of view, those positive psychology interventions that had been applied on women with breast cancer were searched and analyzed. The used methodology was also a systematic review, and results showed that there were few and heterogeneous positive psychotherapies used among this type of population. Five groups of positive psychotherapies could be distinguished: mindfulness-based psychotherapies, meaning-making interventions, writing about positive emotions, psycho-spiritual interventions, and a hope therapy. Therefore, the empirical exploration of the efficacy of a positive psychotherapy on cancer survivors was found to be necessary. This psychotherapy was aimed at reducing stress symptoms through the promotion of posttraumatic growth in distressed cancer survivors. Results showed that the psychotherapy was capable of both promoting posttraumatic growth and reducing stress symptoms. In regards to posttraumatic growth, it is also discussed about its authenticity. Empirical data showed that the relatives of those who had undergone cancer corroborated the posttraumatic growth reported by the cancer survivors.
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Batty, Elizabeth. "Fusion genes in breast cancer." Thesis, University of Cambridge, 2012. https://www.repository.cam.ac.uk/handle/1810/241721.
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Fusion genes caused by chromosomal rearrangements are a common and important feature in haematological malignancies, but have until recently been seen as unimportant in epithelial cancers. The discovery of recurrent fusion genes in prostate and lung cancer suggests that fusion genes may play an important role in epithelial carcinogenesis, and that they have been previously under-reported due to the difficulties of cytogenetic analysis of solid tumours. In particular, breast cancers often have complex, highly rearranged karyotypes which have proved difficult to analyse using classical cytogenetic techniques. The aim of this project was to search for fusion genes in breast cancer by using high-resolution mapping of chromosome rearrangements in breast cancer cell lines. Mapping the chromosome rearrangements was initially done using high-resolution DNA microarrays and fluorescence in-situ hybridisation, but moved to high-throughput sequencing as it became available. Interesting candidate genes identified from the mapped chromosome rearrangements were investigated on a larger set of cell lines and primary tumours. The complete karyotypes of two breast cancer cell lines were constructed using a combination of microarrays, fluorescence microscopy, and high-throughput sequencing. A number of potential fusion genes were identified in these two cell lines. Although no expressed fusion genes were found, the complete karyotypes gave insight into the number and mechanisms of chromosome rearrangement in breast cancer, and identified interesting candidate genes which may be of importance in tumourigenesis. Two genes which were fused in other breast cancer cell lines, BCAS3 and ODZ4, were disrupted by chromosome rearrangements and identified as interesting candidate genes in tumorigenesis. A bioinformatic pipeline to process high-throughput sequencing data was set up and validated, and shown to more accurately predict fusion genes than other methods, and can be used to investigate further cell lines and tumours for recurrent fusion genes. The pipeline was used to analyse data from 3 other breast cancer cell lines and predict chromosomal rearrangements and fusion genes, several of which were found to be expressed. Of the fusions predicted in the cell line ZR-75-30, 7 expressed fusion genes were identified, and may have functional significance in breast cancer.
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Hinshelwood, Rebecca Garvan Institute of Medical Research UNSW. "Epigenetic changes in breast cancer." Publisher:University of New South Wales. Garvan Institute of Medical Research, 2009. http://handle.unsw.edu.au/1959.4/43633.
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Changes in the epigenetic landscape are widespread in neoplasia, with de novo methylation and histone repressive marks commonly occurring in association with gene silencing. However, understanding the dynamics of epigenetic changes is often hindered due to the absence of adequate in vitro model systems that accurately reflect events occurring in vivo. Human mammary epithelial cells (HMECs) grown under standard culture conditions enter a growth arrest termed selection, but a subpopulation is able to escape from arrest and continue to proliferate. These cells, called post-selection cells, have many of the hallmarks seen in the earliest lesions of breast cancer, including transcriptional silencing and hypermethylation of the p16INK4A tumour suppressor gene. The overall aim of my thesis was to use post-selection HMECs as model system to identify and dissect the mechanism involved in early epigenetic aberrations. Firstly, using a microarray approach, I found that multiple members of the TGF-β signalling pathway were concordantly suppressed in post-selection cells, and this was associated with functional disruption of the TGF-β pathway. Interestingly, concordant gene suppression was not associated with aberrant DNA methylation, but with repressive chromatin remodelling. Secondly, to further understand the mechanism underpinning epigenetic silencing, I demonstrated using laser capture technology, that p16INK4A silencing is a precursor to DNA methylation and histone remodelling. Thirdly, I found that individual post-selection HMEC strains during the early passages shared a common 'wave' pattern of regional-specific methylation within the p16INK4A CpG island. Interestingly, the 'wave' pattern of early de novo methylation correlated with the apparent footprint of nucleosomes within the p16INK4A CpG island. Lastly, to further characterise the properties of the HMEC culture system, I demonstrated that post-selection cells do not possess a natural tumour-inducing property when transplanted into the mammary fat pad of immunocompromised mice. However, post-selection HMECs were associated with high expression of a variety of stem/progenitor markers, as well as stem/progenitor associated polycomb genes, thus demonstrating that these cells share some common features of stem/progenitor cells. The research presented in this thesis demonstrate that epigenetic changes occur early in the growth of post-selection HMECs and many of these changes are common in breast cancer.
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Lidgren, Mathias. "Health economics of breast cancer /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-202-6/.
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González-Zuloeta, Ladd Angela Maria. "Genetic determinants of breast cancer." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10525.
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Gould, David R. (David Ross). "Prolactin in human breast cancer." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41006.
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The function of prolactin in human breast cancer was studied using four different approaches. First, purification and characterization of the prolactin receptor from breast cancer cells indicated that the receptor has a molecular mass of 88 000 Da, 67 000 Da being protein, and the other 21 000 Da presumably carbohydrate. Secondly, prolactin was tested for mitogenic activity in breast cancer in vitro. No consistent mitogenic response to prolactin could be demonstrated in these experiments. Thirdly studies upon the regulation of the prolactin receptor in breast cancer cells indicated that the prolactin receptor is stimulated by lactogen, estrogen and progesterone at the protein level. Estrogen, progesterone, thyroid hormone, and forskolin (but not lactogen) increase prolactin receptor steady state RNA levels, and the phorbol ester PMA and retinoic acid inhibited receptor RNA levels. However, effects at the RNA level were of a much lesser magnitude than effects at the protein level. Mechanisms other than transcriptional regulation alone are likely involved in prolactin receptor regulation. Fourthly, prolactin receptor and prolactin inducible protein/gross cystic disease fluid protein (PIP/GCDFP-15) RNA levels were examined in breast cancer tumors. Highly significant correlations were observed between the prolactin receptor and the progesterone receptor; the prolactin receptor and PIP/GCDFP-15; and PIP/GCDFP-15 and progesterone receptor.
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Udeozo, Uchechukwu Kanayochukwu Ifeatu. "Angiotensin II and breast cancer." Thesis, Queen Mary, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405894.
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Rigby, Janette Elizabeth. "An epidemiology of breast cancer." Thesis, Lancaster University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311870.
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Lee, Ann Siew Gek. "Chromosomal aberrations in breast cancer." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276849.
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Afzal, Maryam. "Breast cancer and oxidative stress." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/55856/.
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Endocrine and anti-EGFR strategies are used to treat breast cancer. Unfortunately, resistance can be acquired. Deciphering resistance mechanisms remains essential to design treatments for this adverse state. Oxidative stress is the cellular imbalance of pro-oxidants (promoting cell death) and antioxidants (facilitating cell survival and chemotherapy/radiotherapy resistance). However, it remains unexplored whether endocrine or anti-EGFR resistance also associates with altered redox balance. In this project, redox balance was examined using in vitro human resistant breast cancer models TAMR, FASR, X-MCF and NEW DUBS, comparing with responsive w/tMCF7 cells using microarray analysis, PCR, and TAC, ROS, or MTT assays. Pro-oxidant levels increased significantly in all resistant models but this did not impact adversely on growth. Significantly increased antioxidant levels were also observed in all resistant models, perhaps limiting pro-oxidant increases to maintain cell survival. Antioxidants were also significantly induced by antihormones in w/tMCF7 cells that may limit apoptosis with early treatment. Expression of 15 antioxidant genes increased in resistant cells spanning multiple resistant states. While gefitinib challenge revealed many antioxidant genes were EGFR/kinase signalling-regulated in TAMR cells, gefitinib and further signal transduction inhibitors (STIs) indicated total antioxidant capacity was not. Thus, additional genes/signalling probably drive increased antioxidants in resistant cells future deciphering and depletion of antioxidants could feasibly block cell survival in multiple resistant states. Several STIs further increased pro-oxidants in TAMR cells, indicating oxidative stress was also not EGFR/kinase-promoted since STIs also further increased antioxidant capacity, this may again limit pro-oxidant increases and hence apoptotic effect. Importantly, the thesis revealed resistant cells may be particularly sensitive to agents inducing excessive oxidative stress. Redox balance and feasibility of agents influencing redox remains complex. However, new findings and concepts emerging from this thesis are worthy of future exploration for potential treatments for resistance to endocrine/anti-EGFR agents.
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Fedele, Vita. "Polycomb proteins and breast cancer." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/3584.
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In the Western world, breast cancer is the most frequent malignancy in women and still the leading cause of cancer related deaths, therefore, a better understanding of the disease is needed. Adequate therapeutic targets for all breast cancer types have not been identified yet, and patients with the same type of cancer have often different outcomes. Polycomb proteins are emerging as important factors involved in breast cancer formation. Polycomb proteins play a crucial role in embryogenesis, early development, stem cell renewal and establishing and maintaining cell identity. Their alteration leads to mis-regulation of several important cellular factors including tumour suppressors, DNA repair factors, cell cycle regulation factors and cell-cell interaction factors. In this thesis the importance of several polycomb proteins in breast cancer has been investigated. The effect of EZH2 knockdown has been tested in breast cancer cell lines expressing different level of the protein and with different features. The results obtained are in line with other studies and suggest that the effect of EZH2 down-regulation in breast cancer cells is dependent on cellular context. In vitro experiments, using both established breast cell lines and primary epithelial cells have been used for investigating the importance of CBX8 in breast cancer. The results obtained showed that the polycomb proteins CBX8 does not play a central role in malignant transformation of the mammary epithelial cells tested.
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Brosseau, Carole. "Vitamin D and breast cancer." Thesis, St George's, University of London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546799.
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Hadad, Sirwan Mohammed. "Metformin, AMPK and Breast Cancer." Thesis, University of Dundee, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521704.
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Stanway, Susannah J. "Steroid Sulphatase and Breast Cancer." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511888.
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Ng, Jia Nian, and 黃嘉年. "RNF168 expression in breast cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206551.
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Background: Breast cancer is the commonest female cancer. DNA double-strand breaks (DSBs) associated proteins such as BRCA1 have been shown to be involved in tumourigenesis of breast tissue. One of the key regulators of DSBs, the RING Finger Protein 168 (RNF168), controls DNA damage responses (including the manipulation of homologous recombinant and non-homologous end-joining repair) which are responsible for correction of errors that occur during DSBs in order to maintain genomic stability. The nature of this protein suggests that RNF168 may play an important role in development of breast cancer.
Material and methods: This study investigated the relationship of RNF168 expression in breast cancer by immunohistochemistry staining of 118 breast cancer samples in tissue microarray. The nuclear stain and cytoplasmic stain of the sections were assessed. Nuclear localization score was obtained and correlated with clinico-pathological features of the patients.
Results: Immunohistological staining of RNF168 was successful in 99 cases of the tested breast cancer specimens. The expression of RNF168 was found to be significantly correlated with the occurrence of breast cancer metastasis (p=0.032). Strong expression of the protein was also found to be significantly associated with poorer breast cancer prognosis (p=0.033). In addition, correlation analysis also showed marginal correlation between nuclear localization of RNF168 with the age of patients at their first disease diagnosis (p=0.061).
Conclusion: RNF168 might play a critical role in promoting breast cancer metastasis during the advanced stage of breast cancer, which results in poor disease prognosis. Detailed mechanism involved in metastasis promotion remained to be revealed in further study.published_or_final_version
Pathology
Master
Master of Medical Sciences
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Donaghy, Kathleen B. "Biopsychosocial factors in breast cancer." Virtual Press, 1997. http://liblink.bsu.edu/uhtbin/catkey/1115723.
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In the treatment of early stage breast cancer, both mastectomy and lumpectomy followed by radiation therapy have been recognized as having similar survival rates. Increasingly, women are being given the opportunity to choose which of these surgical treatment options they wish to pursue. Decisions tend to be made rather quickly, and some women may later regret their treatment choice. In this study, an instrument (Breast Cancer Treatment Inventory (BCTI)) was developed that identified five primary sources of influence that affect women's breast cancer treatment decisions: cosmetic outcome, preparedness, physician's choice, short-term effects, and long-term effects. Items were generated and refined by oncology professionals and breast cancer survivors, followed by a pilot study conducted with members of a breast cancer support group. The resulting 28-item scale was completed by 139 early stage breast cancer patients. A series of oblique factor analyses yielded a five-factor solution with reliabilities ranging from .66 - .87. Content validity was enhanced by involving oncology experts and women with breast cancer in the item generation procedures. Use of the BCTI may assist women through a methodical and effective decision-making process. The BCTI may also be appropriate for research studiesinvolving the process and prediction of treatment selection since it meets requirements for ease of administration, brevity, reliability, and validity.Department of Counseling Psychology and Guidance Services
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El-Rehim, Dalia M. Abd. "Immunophenotype characteristics of breast cancer." Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403444.
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Godden, Judith Lilian. "Growth regulation in breast cancer." Thesis, University of Glasgow, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387795.
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Sousa, Cristovao. "Huntington disease and breast cancer." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114823/document.
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La maladie de Huntington (MH) est une maladie neurodégénérative autosomale dominante causée par une expansion anormale de CAG dans le gène codant la huntingtine (HTT) qui se traduit dans la protéine HTT par une répétition de polyglutamine, entrainant la mort neuronale. Néanmoins, la MH entraine aussi le développement de symptômes périphériques comme la HTT est une protéine exprimée de façon ubiquitaire. Notamment, la MH a été associé à une plus faible incidence des cancers, mais les mécanismes sous-jacents ne sont pas décrits. Nous avons étudié le rôle de HTT mutée et sauvage dans le cancer du sein, où la protéine est fortement exprimée. Des modèles murins de cancer du sein (MMTV-PyVT et MMTV-ErbB2) exprimant la HTT mutée (souris knock-in transportant 111 GAC) développent des tumeurs mammaires agressives par rapport aux souris exprimant la HTT sauvage. La transition épithéliale-mésenchymateuse est accélérée avec une augmentation de la motilité cellulaire ainsi que de la formation de métastases. Ces tumeurs accumulent le récepteur tyrosine-kinase HER2 à la membrane, en raison d'un défaut d'endocytose dynamine-dépendante en présence de la HTT mutée. La signalisation accrue de HER2 est responsable de l'agressivité des tumeurs exprimant la HTT mutée, comme en témoigne le traitement trastuzumab, un anticorps dirigé contre HER2 qui restaure la motilité et l'invasion des cellules tumorales porteuses de la mutation responsable de la MH. La HTT sauvage a elle-même un rôle protecteur dans le cancer, retardant l’apparition des métastases en raison d'un potentiel rôle dans l’adhésion intercellulaire. Ainsi, notre travail met en évidence des rôles clés de la HTT mutée et sauvage au cours de la progression du cancer du seinHuntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal CAG expansion in the huntingtin (HTT) gene. The corresponding polyglutamine expansion in the HTT protein causes specific neuronal death, but the consequences of HTT mutation in other tissues are less well understood. Nevertheless, HD mutation causes peripheral symptoms as HTT is an ubiquitous protein. HD was associated to lower cancer incidence, however, the mechanisms behind this effect were not described. Here we have studied the role of wild-type and mutant HTT in breast cancer, where we found the protein to be highly expressed. We demonstrate that mouse breast cancer models (MMTV-PyVT and MMTV-ErbB2) expressing mutant HTT (knock-in mice carrying 111 CAGs) develop aggressive mammary tumors as compared to control mice. Epithelial-to-mesenchymal transition is enhanced with subsequent increased cell motility and metastasis. These tumors accumulate tyrosine-kinase receptor HER2 at the membrane, due to a dynamin-dependent endocytosis defect in the presence of mutant HTT. HER2 enhanced signaling is responsible for the aggressiveness of the mutant HTT expressing tumors, as demonstrated by Trastuzumab treatment, an antibody against HER2 that restores motility and invasion in tumor cells carrying HD mutation. The wild-type HTT has itself a protective role in cancer, inhibiting metastasis due to a possible role in cellular junction maintenance. Thus, our work unravels a key role of HTT in breast cancer progression, with the mutant HTT triggering the development of aggressive and metastatic tumors
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Dawson, Sarah-Jane. "Molecular biomarkers in breast cancer." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609742.
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Md, Hashim Fariesha. "Invadopodia formation in breast cancer." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/invadopodia-formation-in-breast-cancer(faf29295-e355-43a8-945b-9d17a3992ed6).html.
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Cancer progression can be driven by signalling via growth factors such as hepatocyte growth factor (HGF) and by the surrounding microenvironment. During initial tumour expansion intratumoral hypoxia can develop due to inadequate vasculature supply. To resist the negative effect of hypoxia, cells increase expression of transcription factor hypoxia-inducible-factor-1 (HIF-1α). However, little is known about how HIF-1α might influence the invasive behaviour of the cancer cells. Cell invasion requires actin cytoskeletal reorganisation and cells are thought to utilise specialised membrane protrusions termed invadopodia. Rho family GTPases Rac and Cdc42 through interaction with effector proteins p21-activated kinases (PAKs) are known to regulate actin cytoskeletal dynamics. Indeed, PAK1/2 are over-expressed in breast cancer however the role of PAK1/2 in invadopodia formation has not been fully investigated. This project sought to investigate the relationship between growth factor signalling, induction of HIF-1α expression and PAK activity during invadopodia formation in MDA-MB-231 cells. Analysis revealed that increased invadopodia formation can be induced by HGF. Furthermore, increasing levels of HIF-1α using dimethyloxaloylglicine (DMOG) treatment or overexpression of GFP-HIF-1α correlated with increased invadopodia activity that was dependent upon the expression of HIF-1α. Subsequent studies revealed that PAK1 and 2 are required for both HGF and DMOG induced invadopodia formation. However, whilst PAK1/2 were activated downstream of HGF, there was no change in PAK1/2 expression levels or activity following DMOG treatment. Interestingly both DMOG treatment and HIF-1α overexpression did lead to up-regulation of cytoskeletal protein expression including β-PIX. β-PIX interacts with PAK1 but has not been previously linked to invadopodia formation. It is shown here for the first time that a reduction in treatment. Overall, these studies demonstrate the dynamite the dynamic nature of ivadopodia formation; identity novel regulators of invadopodia activity and highlight the direct role of hypoxia in cell invasion.
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Lahart, I. M. "Physical activity and breast cancer." Thesis, University of Wolverhampton, 2014. http://hdl.handle.net/2436/332113.
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Background: Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer death among females, both worldwide and in the UK. Although, UK incidence of breast cancer is rising, breast cancer mortality rates are falling, due largely to early detection and improved treatment. As a result there are more women living with a diagnosis of breast cancer than ever before. Due mainly to side-effects of adjuvant therapy, breast cancer patients may require diagnostic, therapeutic, supportive or palliative services many years post-diagnosis, which poses a major challenge to already stretched healthcare services. Accordingly, effective and inexpensive interventions that can alleviate treatment side-effects, improve health, quality of life and potentially reduce risk of early mortality are required for breast cancer patients. Awareness of the positive influence that physical activity can have on breast cancer development and outcome is an important determinant of physical activity levels. A higher level of physical activity before and after breast cancer diagnosis is related to a lower risk of all-cause and breast cancer-related mortality. Randomised controlled trials have reported beneficial effects of physical activity interventions on outcomes relating to health, quality of life and mortality risk among breast cancer survivors. Aims: The present project aimed to: 1) assess awareness of the role of physical activity on breast cancer risk and the sufficiency of physical activity undertaken in women attending the NHS breast screening programme (NHSBSP), 2) compare physical activity levels of women at different stages of breast cancer pathway, 3) investigate the effects of a low-cost six-month home-based physical activity intervention on physical activity, body mass, health-related quality of life (HRQoL), insulin resistance and blood lipid profiles of breast cancer survivors and 4) assess the effects of our home-based intervention on cardiorespiratory fitness in a subset of breast cancer survivors. Methods: A total of 309 volunteers (188 NHSBSP attendees, 41 breast cancer patients undergoing chemotherapy and 80 post-treatment breast cancer survivors) participated in the current project. Physical activity was assessed via the International Physical activity Questionnaires (IPAQ). In studies one and two, Body mass and body mass index (BMI) were assessed directly in chemotherapy patients and breast cancer survivors, and indirectly from self-reported values in NHSBSP attendees. While in study three, body fat percentage was measured via bioelectrical impedance analysis, HRQoL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire and fasting blood samples were taken to measure lipid, glucose and insulin concentrations at baseline and post-six month home-based physical activity intervention. In study four, a random subsample of 32 breast cancer survivors undertook an exercise tolerance test to establish peak oxygen uptake values. Results: A high proportion (70%) of NHSBSP attendees engaged in low-moderate levels of physical activity and performed low amounts of recreational physical activity. Attendees demonstrated high awareness (75%) of the role of physical activity in reducing breast cancer risk but those categorised as “low activity” were significantly unaware of insufficiency of activity (p<0.05). Chemotherapy patients and breast cancer survivors had significantly lower levels of total physical activity than NHSBSP attendees (p<0.001 and p<0.05, respectively). The randomised controlled trial revealed significant improvements in total physical activity, body mass (p<0.05), BMI (p<0.05) HRQoL (breast cancer subscale, p<0.01; trial outcome index, p<0.05) and total (p<0.01) and low-density lipoprotein (p<0.05) cholesterol concentrations in the intervention group compared to usual care, and significant improvements in cardiorespiratory fitness (p<0.05) in a subsample of breast cancer survivors allocated to intervention. Conclusions: Physical activity interventions that incorporate strategies aimed at increasing awareness of recommended physical activity guidelines may be required in populations at risk of breast cancer. A relatively large proportion of women at risk of breast cancer may not be sufficiently exposed to the potential benefits of physical activity on breast cancer outcomes. Post-treatment breast cancer patients may be more receptive to physical activity interventions as the negative effects of chemotherapy begin to resolve, and therefore, may benefit from physical activity interventions. Results suggest that a low-cost home-based physical activity intervention with counselling and telephone support can improve the health and HRQoL of breast cancer survivors, which may in turn potentially reduce risk of breast cancer and cardiovascular disease-related mortality. Given the encouraging results and its highly portable and feasible nature, our intervention represents a promising tool for use in health and community settings to benefit large numbers of breast cancer survivors. The current project supports the inclusion of physical activity promotion as an integral component for the management and care of breast cancer survivors.
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Mcintosh, Stuart Andrew. "Surgical techniques in breast cancer." Thesis, Ulster University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626857.
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Surgery forms a key part of the contemporary treatment of breast cancer. Techniques for the surgical management of breast cancer continue to evolve, and in current practice aim to achieve optimal control of the breast tumour while minimising morbidity to tile patient and achieving the best possible aesthetic and quality of life outcomes. Research into specific surgical techniques with these aims was carried out in several hospitals and universities across the United Kingdom. This research focused on two specific areas: sentinel lymph node biopsy (SLNB) in breast cancer, and reconstructive surgery following mastectomy. Feasibility studies were carried out evaluating different techniques for SLNB, examining the role of routine lymphoscintigraphy in SLNB, and the use of SLNB in screen-detected impalpable breast cancer. Immunohistochemical studies were carried out to provide further validation data in support of the sentinel node hypothesis. These studies have informed both clinical practice and the design of subsequent research studies in SLNB. In breast reconstruction, scientific data regarding reconstruction techniques and oncological effects of reconstruction were evaluated, and the issues surrounding the management of breast cancer in the previously augmented breast were assessed. Outcomes in a large series of immediate breast reconstructions utilizing a novel surgical technique were reported, demonstrating that this was a safe and effective technique for immediate reconstruction in both the settings of risk-reducing mastectomy and therapeutic mastectomy for the treatment of breast cancer. Finally, validation data in support of a potential new visualisation tool (stereophotogrammetry) for the objective assessment of aesthetic outcomes in breast reconstruction surgery were described. The work has made a significant contribution to knowledge in both of these fields.
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Dhondalay, G. K. R. "Systems biology of breast cancer." Thesis, Nottingham Trent University, 2013. http://irep.ntu.ac.uk/id/eprint/316/.
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Breast cancer, with an alarming incidence rate throughout the globe, has attracted significant investigations to identify disease specific biomarkers. Among these, oestrogen receptor (ER) occupies a central role where overexpression is a prognostic indication for breast cancer. The cross-talk between the responsible contenders of ER-associated genes potentially play an important role in the disease aetiology. Investigation of such cross talk is the focus of this thesis. The development of high throughput technologies such as expression microarrays has paved the way for investigating thousands of genes at a time. Microarrays with their high data volume, multivariate nature and non-linearity pose challenges for analysing using conventional statistical approaches. To combat these challenges, computational researchers have developed machine learning approaches such as Artificial Neural Networks (ANNs). This thesis evaluates ANNs based methodologies and their application to the analysis of microarray data generated for breast cancer cases of differing oestrogen receptor status. Furthermore they are used for network inferencing to identify interactions between ER-associated markers and for the subsequent identification of putative pathway elements. The present thesis shows that it is possible to identify some ER-associated breast cancer relevant markers using ANNs. These have been subsequently validated on clinical breast tumour samples highlighting the promise of this approach. This thesis will also demonstrate the novel application of ANNs in systems biology of ER, PR and Her2. Furthermore in this research, the integration of ER, PR and Her2 systems have been undertaken to represent a broader view of the breast cancer system. Finally, this thesis will discuss the advantages, limitations, potential application and future potential applications of the methods evaluated.
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Chan, Ching Wan. "Apoptosis in breast cancer cells." Thesis, University of Bristol, 2004. http://hdl.handle.net/1983/8971525c-0de9-4e21-9677-ab73d61ae65c.
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Chuprovska, Yu Ya. "Characteristics of breast cancer progression." Thesis, БДМУ, 2020. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18208.
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Tuttle, Traci R. "Placental lactogen in breast cancer." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378196610.
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