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Li, Pei-Xiang. "Molecular approaches to breast cancer treatment." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0023/NQ50092.pdf.
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Abraham, J. E. "The pharmacogenetics of breast cancer treatment." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595327.
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The core project in this thesis is the translational study PGSNPS, which aimed to investigate the pharmacogenetics of breast cancer chemotherapy in the adjuvant setting. Blood or saliva samples were collected from over 2300 patients, who were recruited during a 4 year period. The trial design was adapted to a GWAS approach. The combination of high quality genotype data and detailed clinical information allows this collection to be a useful resource not only for pharmacogenetic analysis but for investigation of prognosis and susceptibility in future analyses. I also examined the role of candidate gene analysis in the identification of variants associated with survival and susceptibility analysis. Candidate gene analysis of the prostaglandin pathway investigated the potential role of key genes in this pathway and their association with breast cancer susceptibility and survival. There was little evidence that common variants are associated with modest risks of breast cancers and no evidence for association with overall survival (OS) for any tagSNP studied. The metabolic enzyme cytochrome P450 2D6, (CYP2D6), is involved in the metabolism of tamoxifen to its active metabolites. I examined the role of the CYP2D6 gene in breast cancer specific survival (BCSS) and OS in tamoxifen treated breast cancer patients. One putative poor metaboliser (PM) CYP2D6*6 may be associated with decreased BCSS and OS, but the prior probability of such an association is low. All other putative functional variants showed no association. The evidence from this study does not support implementation of routine CYP2D6 testing pre-treatment to guide choice of hormone therapy.
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Whitman, Birgit. "Breast cancer : patient narratives and treatment methods." Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/2969/.
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This thesis concentrates on the treatment of women with breast cancer in the 19th and 20th century. It analyses written published patient narratives linking them with clinical developments. Medical history holds a rich source of information providing the view of the clinician. This includes case reports and case series from one surgeon or one hospital for the earlier period of the study and has progressed to the double blind randomised controlled trial that dominates comparative research today. There is an imbalance in the material available for the analysis of patients’ perceptions of their treatment. The patient view is not represented well in the history of medicine. This thesis attempts to provide a more complete assessment of the developments in breast cancer treatment by including the patient’s view. Three narratives provide an insight into the perception of women who were treated with breast cancer prior to the introduction of anaesthesia and infection control. The novelist, Fanny Burney (1752-1840), underwent a mastectomy in 1811. In a letter to her sister she wrote about her experience providing details of her diagnosis and treatment. In comparison, Emily Gosse (1806-1857) refused a mastectomy for her breast cancer and sought alternative treatment with caustics. Her husband, Phillip Gosse and friend, Anna Shipton, wrote narratives about Emily’s suffering. A third narrative provides the view of a woman with breast cancer who received no treatment and died of metastatic breast cancer; Zelie Martin died in 1877. These narratives were linked to a case report by Lorenz Heister (1683-1758). Heister described the procedure for amputation of the breast in detail. His method prevailed until new scientific developments in surgery such as anaesthesia and infection control improved the short-term survival of patients and enabled surgeons to operate sooner with a greater attention to detail.
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Bossaer, John B., and Christian M. Thomas. "Adjuvant Treatment of Newly Diagnosed Breast Cancer." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/2313.
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Keim, Rebecca. "Treatment-Induced Breast Cancer Dormancy and Relapse." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3500.
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When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor relapse. These include: 18Gy/day RT, chemotherapy combined with the blockade of autophagy, and combined chemo-immunotherapy. Follow-up studies are needed to determine the feasibility of preventing tumor relapse by prolonging tumor dormancy versus eliminating dormant tumor cells.
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Thanoon, David. "Computational framework for local breast cancer treatment." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14387/document.
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Le cancer du sein est le cancer le plus fréquent chez les femmes. Il y a une multitude de solutions proposées concernant une éventuelle intervention médicale pour le cancer du sein ‐ une en particulier est la chirurgie mammaire conservatrice (tumoréctomie). Le but de la tumoréctomie est de parvenir à un contrôle local du cancer, ainsi que de préserver une forme du sein qui satisfait les besoins esthétiques de la femme. Bien que ces objectifs sont généralement atteint, il reste encore parfois des résultats inattendus,tels qu'une tumeur récurrence locale, ou des résultats cosmétiques insuffisants.L'objectif de cette thèse est de proposer une plateforme de calcul, qui contribue à la tumoréctomie. Cela comprend:1) Une étude de la dynamique de croissance des tumeurs du sein.2) Une étude sur la prédiction du contour du sein grâce a la chirurgie virtuelle.3) Un modèle de calcul de la forme finale du sein après cicatrisationBreast cancer is the most common cancer among women in the developed as well as the developing countries. There are a plethora of proposed solutions regarding possible medical interventions for breast cancer–one in particular is Breast Conserving Therapy (BCT). BCT comprises of complete surgical excision of the tumor (partialmastectomy), and post-operative radiotherapy for the remaining breast tissue. This is a feasible treatment for most women with breast cancer. The goal of BCT is toachieve local control of the cancer, as well as to preserve breast shape that appeases awoman’s cosmetic concerns. Although these goals are usually achieved, there are still occasional unexpected results, such as reexcision of the tumor due to a positive margin assessment, tumor local recurrence, unsatisfactory cosmetic results, and breastpain. Other than surgical experience and judgment, there are currently no toolswhich can predict the outcome of partial mastectomy on the contour and deformity of the treated breast. The objective of this dissertation is to propose computational framework, which contributes to BCT operations, this was achieve by exploring two areas.On the one hand we developed a multiscale model adapted for breast cancer tumor growth, ductal carcinoma in situ (DCIS). The model features included: nutrients growth limitation, wall degradation enzyme and HER2 chemical expression tumor phenotype. Our model successfully simulate some pattern of DCIS carcinoma.Among the interesting result we showed that the enzyme contributed to a greater tumor size and that when HER2 was over expressed, the growth limiting factor wasthe EGFR. On the other hand, we developed a virtual surgery box to simulate BCT surgery. The box will input MRI patient data and will output cosmetic and functional indicator to rate the impact of the surgery. It appears that stiffness of the tissue, resection radius as well as the lump quadrant location are the most sensitive parameters to the indicators. A healing model was also embedded to simulate the wound closure after resection, this model was stress dependent and illustrate anasymmetric wound closure progression.The tools developed in this research allows a new type of field convergence between the surgery and computation field. At the local level it will allow surgeons and patient to be able to communicate on the pertinence and necessity of performing alumpectomy surgery, enabling to anticipate the possible outcome of the operation.On the global aspect this type of tool gives birth to a new type of field: computational surgery, where computer scientist and surgeons work hand in hand to provide the best and the most reliable service to the patients
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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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Fleischer, Anne. "Exploratory study of breast cancer survivors' lived experience : activity engagement during and after breast cancer treatment." Diss., NSUWorks, 2015. https://nsuworks.nova.edu/hpd_ot_student_dissertations/34.
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The aim of this study is to describe breast cancer survivors' experiences and the associated meanings participating in their important activities during and after breast cancer treatment and the relationship among the survivor, environment, occupation, and performance, using a concurrent mixed method design. Ten survivors between the ages of 45 and 64 with Stage I, II, or III breast cancer who had been treated consecutively with surgery, chemotherapy, and radiation therapy were recruited for the study. Each survivor completed the Activity Card Sort-modified scoring system (ACSm) during the first and last week of radiation therapy and 3 and 6 months post radiation therapy. Additionally, each survivor participated in a semi-structured interview at the end of radiation therapy and 6 months afterwards. Qualitative data was analyzed using interpretative phenomenological analysis (IPA) to understand the survivors' experiences participating in their most important activities. The means and standard deviations of the proportion of activities resumed for the participants' global and category activities were calculated at each time point. A desire to resume participation in meaningful activities emerged from the data and demonstrated the interrelationship between environment, person, and occupation. Themes from the last week of radiation were (a) individual outlook influences how activities are approached, (b) social support reduces the stress of life, (c) side effects influence how activities are completed, and (d) personal and treatment stresses and struggles influenced their perspectives on life. At 6 months post radiation therapy, the themes were (a) emotional effect on activities, (b) life after cancer has changed due to cancer diagnosis and treatment, and (c) side effects continue to influence daily activities. Using the seven stages of analyzing mixed method data developed by Onwuegbuzie and Teddlie (2003), the qualitative and quantitative data were integrated. The results illustrated that the participants resumed a greater proportion of instrumental activities, which were reported consistently as one of their five most important activities. Additionally, supportive extrinsic factors appeared to be more influential in resuming participation important activities than intrinsic factors. Findings from this study support using the Person-Environment-Occupational-Performance (PEOP) model to develop treatment plans for women undergoing or recovering from breast cancer treatment.
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Molenaar, Jacobus. "Treatment decision support for early breast cancer patients." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/77496.
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Smoot, Betty. "Upper extremity function following treatment for breast cancer." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3359582.
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Volpari, Tatiana. "Residual breast cancer metabolic phenotype after docetaxel treatment." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6710/.
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Despite improvements in early diagnosis and prevention, late stage breast cancer is often incurable due to metastasis, tumour relapse, resistance and incomplete response to treatments. Metabolic reprogramming has been recognised as a critical element for cancer cells to grow under hostile conditions and this is likely to contribute towards resistance against chemotherapeutics. This thesis therefore aimed at deciphering the metabolic phenotype of residual breast cancer which survived docetaxel treatment, in vitro and in vivo, quantifying polar metabolite levels and conducting pathway tracing and metabolic flux analysis using stable isotope (¹³C) labelled tracers. \(In\) \(vitro\) residual cells presented a hypermetabolic phenotype characterised by significant accumulation of essential and non-essential amino acids, together with an elicited Warburg effect and an increased antioxidant response based on glutathione production, while in growth arrest. A method to carry out in vivo tracer-based metabolic studies was successfully developed using a breast cancer mouse model. Although the metabolite accumulation outlined in vitro was not observed in vivo, a protective phenotype against oxidative stress was supported by increased flux through the oxidative branch of the pentose phosphate pathway. In conclusion, this thesis demonstrated that metabolic phenotyping is a valid approach to uncover key metabolic alterations in residual tumours both in vitro and in vivo, and could be further exploited to design personalised treatments aimed at restoring sensitivity to therapies.
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Latif, Ay§e. "Genetics of breast cancer susceptibility and treatment response." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525641.
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Ertefai, Benyamin. "Resistance mechanisms during endocrine treatment in breast cancer." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/95393/.
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Prolonged endocrine therapy is the mainstay of treatment for ER+ breast cancer patients. However, resistance develops in many patients which leads to more aggressive disease. Understanding the mechanisms of acquired resistance that emerge as a consequence of prolonged endocrine treatment remains critical. This study aimed to use gene expression profiling to discover induced mechanisms shared by a panel of MCF7-derived acquired resistant cells that underpin endocrine resistant growth. The in vitro panel represents resistance to oestrogen deprivation, tamoxifen or fulvestrant and includes long-term (3year) models to better-mimic clinical endocrine exposure. Affymetrix 1.0ST microarrays detected 572 genes induced in all resistant models versus MCF7. Over-represented ontologies, pathways and functional classification for these genes revealed induction of oxidative phosphorylation (OxPhos) and TCA cycle enzymes in the resistant models, a finding further confirmed by mass spectrometry. Increased oxygen consumption, NADH dehydrogenase and/or cytochrome C oxidase activity was detected in resistant cells, and targeting with OxPhos inhibitors Metformin or Antimycin A confirmed growth-dependency on OxPhos. Western blotting for AMPK (energy sensor) activity and its downstream anabolic targets (ACC, mTOR/P70S6K) showed Metformin reduced fatty acid and protein synthesis in growth-sensitive endocrine resistant cells. In silico analysis inferred clinical relevance since many TCA/OxPhos genes associated with earlier relapse in ER+ and/or tamoxifen treated patients. Monitoring basal glycolysis (extracellular lactate) and growth impact of 2DG or glutamine restriction demonstrated glycolysis and glutaminolysis also contribute to endocrine resistance. The microarrays furthermore revealed that metabolic kinases PCK2, ALDH18A1 and PFKFB2, and components of cell response to Zn were commonly-induced which may additionally help endocrine resistant growth. This study has revealed increased OxPhos arises as a consequence of prolonged endocrine treatment and is a key bioenergetic pathway sustaining resistance. Since resistant growth is Metformin-sensitive, such targeting of this energy pathway (alongside further antihormones or glycolysis/glutaminolysis inhibitors) could help treat resistance.
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Janodien, Fatima. "Proteome signature of breast cancer cells treated with fucoidan." University of the Western Cape, 2016. http://hdl.handle.net/11394/5315.
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>Magister Scientiae - MScBreast cancer is responsible for a large portion of cancer-related deaths. Worldwide, incidence is increasing. Routinely-used treatments for breast cancer are invasive and are associated with a range of side-effects which may affect quality of life. Fucoidan, a marine bioactive compound, found primarily in brown seaweed, has various medicinal qualities. Among its bioactivities studied, it has potent anticancer activity. Despite numerous studies, the mechanism of action of fucoidan on cancer cells remains unclear. This project aims to shed light on the mechanism of action of fucoidan by studying its effect on the MCF7 breast cancer cell proteome. The IC50 obtained for fucoidan treated MCF7 cells was 0.2 mg/ml. Decrease in expression of XIAP and phosphorylation of ERK1/2 was observed, indicating a decrease in inhibition of apoptosis and increased sensitivity to apoptosis, respectively. Literature reports activation of several caspases, including caspase-3, in various cell lines after to fucoidan treatment. Taken together, with data from the current study it can be said that fucoidan treatment led to cell death by apoptosis. SILAC analysis identified over 2000 proteins with more than 1700 at 95% confidence. STRING analysis of enriched proteins revealed 19 cell death related proteins. However, SILAC results were ambiguous with regards to differential protein regulation and should be repeated with lower electrospray ionization flow rates, pairwise and single sample runs, and validation with Western blot analysis of various apoptosis related proteins and biochemical assays.
National Research Foundation
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Desmedt, Christine. "Multi-marker detection approach for improving breast cancer treatment tailoring." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210415.
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the majority of patients with early breast cancer receive some form of systemic adjuvant therapy (chemo-, endocrine, and/or targeted therapy). Despite the increase in adjuvant therapy prescription, little progress has been made with respect to assisting oncologists to determine which breast cancer patients, particularly those deemed at “lower risk” of relapse, require chemotherapy or other systemic therapy and which women can safely be treated with loco-regional treatment alone. For these reasons, the identification of prognostic and predictive markers that will assist the clinician in selecting the most suitable form of medical therapy has become very high priority as well as a real challenge in translational research. \
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Chiwakata, Maynard Tendai. "The synthesis and breast cancer inhibitory activity of cinnamic acid analogues based on the halogenated monoterpene pharmacophore." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1016129.
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Breast cancer is one of the leading causes of death, with mortality rate estimates of 465 000 deaths per annum. It is estimated that 1.3 million women are diagnosed with the disease each year especially in the developing countries. Current chemotherapy relies on the use of high doses of non-specific toxic agents that possess adverse side effects and compromise patient’s compliance and adherence to treatment. Paclitaxel, one of the common drugs used in breast cancer chemotherapy results in sensory and motor neuropathy, whilst hormonal therapy e.g. Herceptin causes severe cardiovascular, gastrointestinal and cutaneous side effects. There has been a demand in developing newer cancer agents that demonstrate selective cytoxicity with minimal effect on normal body tissue. Numerous studies have shown that marine organisms produce a wide range of halogenated compounds that possess cytotoxic properties, and hence can be a source of new drug hits or leads for cancer therapy. Halomon, a polyhalogenated monoterpene from Portieria hornemannii, displayed interesting activity against brain, renal and lung cancer tumours with selective/differential cytotoxicity. This inspired us to focus our project on halogenated monoterpenes isolated from the same Rhodophyta class as P. hornemannii but with particular attention to Plocamium species. Several metabolites have been isolated from P. cornutum, P. corallorhiza and P. suhrii that possess interesting cytotoxicities against a breast cancer cell line (MCF7) and an oesophageal cancer line (WHCO1). The aim of the project was therefore centred at isolating target compounds for preliminary structure-activity studies against a breast cancer cell line, and use this information to synthesize a series of analogues that are more stable than the natural products and yet as active using a fragment-based type approach to map out pharmacophoric elements. Five metabolites were isolated from P. cornutum and five from P. corallorhiza. Cell-based assays were conducted using an MTT assay kit against MCF7 and MDA-MB-231 breast cancer cell lines and (1E,3E,5S,6R)-1,5,6-trichloro-2-(dichloromethyl)-6-methylocta-1,3,7-triene, isolated from P. cornutum was the most active with IC50 values of 3.0 μM and 6.15 μM respectively. Introduction of a terminal aromatic ring to enhance stability, together with varying substituents (H, CH3, CF3, Br, CN, CHO, CHCl2) on position 7 of the molecule, gave rise to a series of cinnamate ester derivatives inspired by (1E,3E,5S,6R)-1,5,6-trichloro-2-(dichloromethyl)-6-methylocta-1,3,7-triene. The analogues were synthesized from their benzaldehyde precursors via Aldol condensation, esterification and Wittig reactions. Their carboxylic acid counterparts were synthesized by hydrolysis of the parent esters in an attempt to promote water solubilities of the analogues. Biological activity assays were then conducted with the cinnamate analogues against the MDA-MB-231 breast cancer cell line using an MTT assay kit. Ester derivatives with -CHO and -CHCl2 functionalities had IC50 values of 43.45 μM and 100.01 μM respectively whilst the other ester derivatives were inactive. It was concluded that either an aldehyde (-CHO) or gem-dichlorides (-CHCl2) is specifically required for cytotoxic activity to be observed. None of the carboxylic acids were active which could have been due to failure of the compounds to enter the breast cancer cells and reach the target site because of their polar nature. Compounds with -CHO and -CHCl2 functionalities were therefore selected for future SARs studies.
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Brand, Juanita M. "The lived experiences of six women during adjuvant chemotherapy for Stage I or II breast cancer." Virtual Press, 2005. http://liblink.bsu.edu/uhtbin/catkey/1317926.
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Latella, Jennifer. "Lymphedema after treatment for breast cancer : a pilot study." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=99343.
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Despite more conservative surgical treatment for breast cancer, lymphedema and arm dysfunction remain sources of significant morbidity. The study for this thesis was conducted to explore methods for defining and identifying lymphedema and arm dysfunction after treatment for breast cancer.In order to establish cut-points in the differences in the sizes of arms to define the presence of lymphedema among women previously treated for breast cancer, the distributions of the differences in the sizes of arms, using measures of circumference and volume, among 40 women with no history of breast cancer were determined. The selected cut-points in the differences were defined as the mean plus one, two, or three standard deviations.
A questionnaire (referred to as the Lymphedema Identification Tool) based on self-reported symptoms was developed to identify women with lymphedema. The Lymphedema Identification Tool and the 'Disabilities of the Arm, Shoulder and Hand' (DASH) questionnaire were sent to 596 women previously treated for stage I or II breast cancer and 50 women attended an evaluation session. At this evaluation session, measurements of the sizes of their arms were made and the Lymphedema Identification Tool and the DASH were repeated. This allowed for the evaluation of test-retest reliability, internal consistency reliability, and criterion validity of the Lymphedema Identification Tool.
From these measurements and responses to the questionnaires, the association between arm dysfunction, as assessed by the DASH questionnaire, and the presence of lymphedema, as determined by the measurements of arm sizes and by women's self-report was determined. In addition, through the development of logistic regression models, the Lymphedema Identification Tool, the DASH questionnaire, age at diagnosis, and body mass index were found to predict the presence of lymphedema, as defined by the measurements of arms.
Lymphedema appears to be a condition associated with a spectrum of symptoms and functional impairment varying from mild to severe. This thesis, even though results are preliminary, suggests a methodology for identifying lymphedema and arm dysfunction.
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MacPhee, Meaghan. "Stabilized combi-molecules for the treatment of breast cancer." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40846.
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We recently developed a novel strategy termed “combi-targeting” that seeks to design “combi-molecules” which are able to not only block EGFR but to also damage DNA. Previous studies that sought to stabilize triazene based combi-molecules were based on masking the 1,2,3-triazene chain with a 2-acetoxymethylene group, leading to the synthesis of RB24 and RB107. The half-lives of these two molecules proved to be only about 5 minutes longer than their parent triazenes. The novel series of molecules presented herein were designed containing hydrolysable groups to modulate the kinetics of their degradation,. These include vinyl, acetoxymethyloxyl, and p-nitrophenol carbamates. Kinetic studies determined that the vinyl carbamate ZRL2 was the most stable of the series. However, its vinyl counterpart ZRL1 designed to be cleaved by a basic neighbouring group was the least stable. The half-lives of all of the other molecules were significantly longer than that of RB107. Specifically, ZRL1 had a half-life approximately 20 min longer and ZRS1, ZRL4, ZRL5 40-55 min longer. The molecules were designed to release a fluorescent aminoquinazoline, FD105, upon degradation. This allowed us to observe its intracellular release by fluorescent microscopy. ZRL1 generated the highest level of fluorescence and its more stable counterpart, ZRL2, produced levels that were barely detectable. Studies directed at determining the dual EGFR-DNA targeting abilities of the molecules showed that: (a) all of the compounds were capable of blocking the EGFR tyrosine kinase activity in an isolated enzyme assay and in MDAMB468 cells, (b) all of the molecules, except for the most stable compound ZRL2, were capable of inducing dose-dependent DNA damage, and (c) induction of DNA damage was associated with cell cycle arrest in G2/M. Using a growth inhibition assay, it was determined that all of the molecules could: (a) block the growth of MDAMB468 cells and (b) preferentially inhibit the EGFR transfeNous avons récemment mis au point une nouvelle stratégie dénommée “combi-ciblage” : cette stratégie est basée sur des agents appelés “combi-molécules”, capables non seulement de bloquer l’EGFR, mais aussi d’induire des lésions de l’ADN. Des études antérieures réalisées au laboratoire et ayant pour but de masquer la chaîne 1,2,3-triazène de certaines combi-molécules par un groupement 2-acétoxyméthylène afin de les stabiliser ont conduit à l’obtention des composés RB24 et RB107. Ces travaux n’ont toutefois pas permis d’augmenter de manière significative les temps de demi-vie de ces deux molécules, puisqu’ils n’étaient supérieurs que d'environ 5 minutes aux temps de demi-vie des molécules triazéniques initiales. Les nouvelles séries de molécules présentées dans cette thèse contiennent un groupement carbamate hydrolysable permettant d’optimiser leur cinétique de dégradation. D’autres modifications ont été également appliquées, notamment l'ajout de différents groupements tels que des vinyl, acétoxyméthyloxyl, et p-nitrophénol carbamates. Ainsi, les études cinétiques ont montré que le vinyl carbamate ZRL2 est le plus stable de ces séries. En revanche, son homologue vinylique ZRL1, conçu pour être clivé par un groupement basique voisin, s’est avéré être le moins stable avec un temps de demi-vie toutefois supérieur d’environ 20 minutes à celui du RB107. Les temps de demi-vie des autres composés se sont significativement allongés, notamment pour ZRS1, ZRL4, et ZRL5, dont les temps de demi-vie dépassent de 40 à 55 minutes celui du RB107. De plus, ces molécules ont été conçues pour libérer un groupement fluorescent de type aminoquinazoline (FD105) au cours de leur dégradation. Par conséquent, nous pouvons observer leur localisation intracellulaire, de même que leur abondance, par microscopie à fluorescence. Ainsi, ZRL1 génère la plus grande quantité de fluorescence, tandis$
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Buijs, Ciska. "Long-term side effects of adjuvant breast cancer treatment." [S.l. : Groningen : s.n. ; University Library of Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/306087480.
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Crane, Elizabeth. "Health Care Systems Factors Affecting Breast Cancer Treatment Choices." Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/156910.
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The purpose of this research was to explore and describe health care systems factors that influence treatment decisions for women with breast cancer in the United States (U.S.) and Norway. The specific aims of the study were to: (a) explore and describe how health care systems processes create barriers and facilitators of breast cancer treatment decisions for patients diagnosed with breast cancer in the US and Norway; and (b) compare and contrast the US and Norwegian system processes to identify advantages and disadvantages of each system as they relate to breast cancer treatments. A descriptive qualitative design was used to address the research aims and questions. Data were collected from key informants from the US and Norway. Content and matrix analysis were the primary descriptive and comparative approaches used for this study. First and second order matrices were created to display and analyze data obtained from key informant interviews. Findings indicate that financing allopathic care is a significant barrier for breast cancer patients within the US and financing CAM therapies are challenging in both countries. While allopathic treatment guidelines for breast cancer care are clearly outlined in both the US and Norway, both countries currently lack CAM treatment guidelines for use in this patient population, leading to inconsistent recommendations provided for patients. There are also significant barriers that prevent patient access of CAM providers, particularly by patients in an in-patient, hospital setting. Ultimately, when evaluating care and treatment plans for women diagnosed with breast cancer, health care providers should appreciate and acknowledge the significant system factors that may act as barriers or facilitators of care.
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Vaidya, Jayant Sharad. "A novel approach for local treatment of breast cancer." Thesis, University College London (University of London), 2002. http://discovery.ucl.ac.uk/18745/.
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Early local recurrence of breast cancer most commonly (over 90%) occurs at the site of the primary tumour. This is true whether or not radiotherapy is given and irrespective of the margin status. Whole-organ analysis of mastectomy specimens on the other hand, reveals that 63% of breasts harbour occult cancer foci and 80% of these are situated remote from the index quadrant. Therefore, these occult cancer foci may be clinically irrelevant and it may not be necessary to treat the whole breast with radiotherapy. This 6-wks long course of post-operative radiotherapy after breast conserving therapy is not only inconvenient and costly, but may cause many women from geographically remote areas to choose mastectomy. Targeted Intraoperative radiotherapy (TARGIT) to the peri-tumoural area alone might provide adequate local control. ‘Intrabeam’ (PeC) is a portable electron-beam driven device that can deliver therapeutic radiation (soft x-rays) in 20-30 minutes within a standard operating theatre environment. The pliable breast tissue - the target - is wrapped around a spherical applicator - the source - providing truly conformal radiotherapy. The prescribed dose is 5 & 20Gy at 1cm and 0.2cm respectively, from the tumour bed. The biologically effective dose is 7-53Gy for α/β=10 and 20-120Gy for α/β=1.5. In our pilot study of 26 patients (age 30-80 years, T=0.42-4.0cm), we replaced the routine post-operative tumour bed boost with targeted intra-operative radiotherapy. There have been no major complications and no patient has developed local recurrence, although the median follow-up time is short at 34 months. The cosmetic outcome is satisfying to both the patient and the clinician. Having established the feasibility, acceptability and safety in the pilot study, we started in March 2000, a randomised trial that compares TARGIT with conventional postoperative radiotherapy for infiltrating duct carcinomas, with local recurrence and cosmesis as the main outcome measures. Patient accrual in this trial has been excellent and it has attracted several international collaborative groups. If proven effective, TARGIT could eliminate the need for postoperative radiotherapy potentially saving time, money and breasts.
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O'Brien, Ciara. "Breast cancer initiating cells in tamoxifen treatment and resistance." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/breast-cancer-initiating-cells-in-tamoxifen-treatment-and-resistance(074d121d-d39b-413d-ae0c-ae54ae1c0293).html.
Full textAbstract:
Resistance to endocrine treatments in oestrogen receptor positive (ER+) breast cancer (BC) significantly contribute to patient morbidity and mortality. ER+ BC constitute 60% of all breast cancers although there is considerable clinico-pathological diversity within this group. Breast cancer initiating cells (BCICs) are implicated in tumour relapse and metastasis and are postulated to drive resistance to standard anti-cancer therapies. However little is known about the sensitivity of BCICs to endocrine therapies. We assessed the effect of tamoxifen treatment and acquired tamoxifen resistance on BCIC frequency in vitro and in vivo using breast cancer cell lines and, importantly, patient derived samples of early and metastatic ER+ breast cancer. In ER+ breast cancer, BCICs may be prospectively enriched in vitro by selecting cells by CD44+/CD24lo/ESA+ phenotype or by mammosphere initiating capacity (MIC). However the gold standard assay to determine BCIC frequency is limiting dilution transplantation in vivo. In the past it has been historically difficult to generate xenograft models of ER+ breast cancer using patient samples. In this thesis, using a novel experimental technique, patient-derived xenografts (PDX) of early and metastatic ER+ BC were generated with almost 85% efficiency in NOD/SCID IL2gammaR-/- (NSG) mice. PDX expressed ER and were able to undergo serial in vivo passage, matching the phenotype of the tumour from which they were derived. In this work, two patterns of response to tamoxifen treatment were observed in ER+ cell lines, patient derived breast cancer samples and xenografts during BCIC assays in vitro and in vivo; Limited Sensitivity (LS) or Resistance (R). In the LS group there was no change or a significant diminution in BCIC frequency in the presence of tamoxifen. In the R group, a significant increase in BCIC frequency was observed in the presence of tamoxifen. Furthermore BCIC activity was shown be enhanced by the acquisition of tamoxifen resistance using cell line models. Cellular populations enriched for BCICs in ER+ cell lines were shown to express low levels of ER compared to non-BCICs. Finally Notch (gamma-secretase inhibitor) and EGFR (gefitinib) pathway inhibitors were tested alone or in combination with tamoxifen against a panel of established and novel cell lines and ER+ patient-derived breast cancer samples for anti-BCIC activity. Tamoxifen treatment can increase BCIC frequency in vitro assays of cell lines and patient-derived samples and in vivo using patient-derived xenografts of ER+ breast cancer. However phenotypic diversity of BCIC may be present within the ER+ BC population. A pharmaceutical strategy to effectively treat BCICs alongside standard endocrine therapy is necessary for the effective future treatment of ER+ breast cancer.
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Giallourou, Natasa. "Watercress as a nutritional adjuvant treatment in breast cancer." Thesis, University of Reading, 2017. http://centaur.reading.ac.uk/76171/.
Full textAbstract:
Breast cancer is a leading cause of cancer related mortality globally, and epidemiological studies suggest a link between healthy nutrition and cancer prevention. Members of the Brassicaceae family, including watercress, have been extensively studied for their anti-cancer and anti-genotoxic potential. Watercress has a complex phytonutrient profile characterised by high levels of carotenoids, flavonols and glucosinolates. Extracts of watercress exhibit strong antioxidant capacity in vitro. Watercress and its components have been associated with the inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis in in vitro cancer cell models. Phenethyl isothiocyanate (PEITC) is a glucosinolate break-down product and watercress is the richest dietary source of it. It has received considerable attention for its anti-cancer properties and has been tested in a number of clinical trials. In this thesis, the effects of crude watercress extract and PEITC on the metabolic and phenotypic responses in breast cancer and healthy breast tissue cell lines were examined. Radiotherapy is the most common treatment modality for breast cancer patients; it functions by killing cancer cells but it simultaneously damages healthy tissues. We set out to examine synergistic responses to irradiation and watercress or PEITC exposures in breast cancer cells and we further investigated whether watercress or PEITC can be protective against radiation induced collateral damage. Watercress and PEITC effectively modulated important cancer cell metabolic pathways associated with anti-cancer endpoints such as cell cycle arrest and DNA damage. In this thesis, PEITC has been shown to enhance the sensitivity of cancer cells to irradiation making the cancer killing process more effective, whereas watercress can protect healthy breast cells from radiation induced damage. These observations appear to be mediated by the ability of PEITC and other phytochemicals in watercress to interact with the antioxidant glutathione. The results obtained from this work remain to be validated in a clinical setting.
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Gross, Brett Patrick. "Therapeutic vaccination for the treatment of metastatic breast cancer." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6119.
Full textAbstract:
Metastatic breast cancer is a leading cause of cancer-related mortality worldwide. While existing interventions are effective at treating localized tumors, disseminated malignancies remain incurable. Vaccine-induced anti-tumor immunity is a promising approach for treating disseminated tumors, as immune responses are systemic, have antigen-restricted cytotoxicity, and generate protective immune “memory” populations.
Our group has developed a novel heterologous prime/boost vaccine protocol that treats established 4T1 murine mammary tumors. Briefly, this approach entails a vaccine prime consisting of tumor lysate antigens encapsulated within poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs). The vaccine prime was followed by a vaccine boost consisting of tumor lysates plus adjuvants. Spontaneous 4T1 lung metastasis was evaluated at a pre-determined endpoint in vaccinated versus untreated mice. Vaccinated mice demonstrated significant, but incomplete, reductions in metastatic tumor burdens relative to untreated control mice.
Encouraged by these results, we evaluated additional vaccine variations with the goal of improving therapeutic responses. The addition of immunomodulatory chemotherapy or checkpoint blockade immunotherapy failed to significantly improve the initial vaccine’s efficacy. Conjugation of streptavidin/biotin complexes to the PLGA MP significantly improved vaccine efficacy, with vaccinated mice demonstrating 88% less metastatic tumor burdens than their untreated counterparts. These findings illustrate that vaccines based upon PLGA MP-mediated delivery of tumor lysates can form the basis of an effective treatment for metastatic breast cancer and suggest that similar approaches may be both efficacious and well-tolerated in the clinic.
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Tse, Ka-ho, and 謝家豪. "A comparison of contralateral breast dose from primary breast radiotherapy using different treatment techniques." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206498.
Full textAbstract:
Breast cancer is the most common cancer among women worldwide. Millions of new breast cancer cases are diagnosed every year, accounting for one-tenth of all new cancer cases. Because of the proof of equivalent efficacy between breast-conserving therapy (BCT) plus radiotherapy and mastectomy, increasing number of patients received breast irradiation during the past three decades, and radiotherapy plays a more and more important role in managing breast cancer. With the advancement of technology, the radiotherapy treatment techniques changed from conventional wedged technique to intensity modulated radiotherapy (IMRT), resulting in an improvement in the dose homogeneity. Regardless of the treatment techniques, peripheral dose to the contralateral breast is inevitable. The possibility of the peripheral dose causing contralateral breast cancer (CBC) has re-attracted the interest. However, the variation of the peripheral dose with different treatment techniques has not been well identified. Thus this study aims to compare the contralateral breast dose from the primary breast irradiation using various radiotherapy treatment techniques and types of shielding.
Six treatment plans by different treatment techniques, including paired physical wedges (PW-P), a lateral physical wedge only(PW-L), paired enhanced dynamic wedges (EDW-P), a lateral enhanced dynamic wedge only(EDW-L), field-in-field tangential opposing (TO-FiF), and inverse-planned intensity modulated radiotherapy (IMRT-IP), were generated using a female Rando phantom. The phantom was treated by all plans, and 15 metal oxide semiconductor field effect transistor(MOSFET)detectors on the surface and inside the contralateral breast were utilized for measuring the contralateral breast dose for each plan. Measurement was repeated with the application of 0.2, 0.3 and 0.5cm lead sheets or 0.5 and 1cm superflab (SF) on the TO-FiF to demonstrate the effect of shielding on the contralateral breast dose.
The measured contralateral breast doses were: 2.05Gy for PW-P, 1.44Gyfor PW-L, 1.51Gyfor EDW-P, 1.52Gyfor EDW-L, 1.25Gyfor TO-FiF, and 1.17Gyfor IMRT-IP, corresponding to 2.35% to 4.11% of total dose. PW-P producedthe highest contralateral breast dose while IMRT-IP producedthe lowest. For the addition of shielding, the doses were: 1.25Gy for no shielding, 0.65Gy for 0.2cm lead, 0.61Gy for 0.3cm lead, 0.49Gy for 0.5cm lead, 0.76Gy for 0.5cm SF, and 0.72Gy for 1cm SF. Lead sheet with 0.5cm thickness most effectively reduced the contralateral breast dose by 60%.All techniques showed that the surface dose was much higher than the dose at depth, and the dose dropped exponentially from the surface to the internal. Low energy radiation constitutes a large portion of the contralateral breast dose, so all types of shielding could decrease the surface dose effectively, but not the internal dose. The radiation-induced CBC risks were estimated to be about 0.77% to 1.36%.
To conclude, it is important that the contralateral breast dose to patients, especially those under 45, is maintained minimal. Therefore, TO-FiF or IMRT-IP are recommended to be the treatment of choices. The used of shielding, either lead or SF, is also advisable.published_or_final_version
Diagnostic Radiology
Master
Master of Medical Sciences
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Hammond, Lynn C. "A qualitative study of treatment issues of eight women with breast cancer." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1645.
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Thesis (Ph. D.)--West Virginia University, 2000.Title from document title page. Document formatted into pages; contains vii, 271 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 225-231).
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Bennett, Barbara Kaye School of Medicine UNSW. "Characterising the nature of postcancer fatigue in women treated for early-stage breast cancer." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/31202.
Full textAbstract:
The problem investigated Four studies investigated the phenomenon of cancer-related fatigue (CRF) in women who had received adjuvant treatment for early-stage breast cancer, with a view to reducing the diagnostic uncertainty surrounding the syndrome and thus facilitating progress in both clinical management and aetiological research. Procedures and results A cross-sectional study of 109 women compared a ???cancer-specific??? self-report questionnaire (FACT-F) (canvassing fatigue symptoms) and a more generic questionnaire (SPHERE) (identifying depression and fatigue). Thirty-seven percent of women reported fatigue. Overall in 20%, fatigue was associated with psychological distress. Seventeen percent of women had fatigue but no depression. A qualitative study utilised focus groups to identify and compare the distinctive features of CRF with those of women with chronic fatigue syndrome (CFS). A similar set of symptoms was found in both groups, including overwhelming fatigue, un-refreshing sleep and subjective concentration problems. However, women with CFS also reported myalgia and arthralgia. Using the Structured Clinical Interview for Neurasthenia- SCIN, the third study compared the symptoms of three groups of women with fatigue: those with CRF, CFS or major depression. The detailed ???interviewer guide??? provided explicit directions for evaluating and classifying symptoms. This study confirmed the core symptom of ???profound fatigue unrelieved by rest???, and additional features that distinguished between the clinical diagnoses. The fourth study compared features of the evolution of clinically-identified fatigue syndromes in women from two prospective cohort studies; women with post-cancer fatigue (PCF) and women with post-infective fatigue syndrome (PIFS). Major conclusions A syndrome of PCF, present at least six months following adjuvant treatment and unexplained by medical or psychiatric disorder was investigated. The characteristics of PCF and those of CFS are very similar, with the fatigue state having indistinguishable descriptors. Longitudinal evaluation of the symptom complexes of PCF and PIFS suggests divergent pathways may be relevant. Co-morbid features like sleep disturbance; physical deconditioning and mood disturbance may be implicated as factors in the evolution and prolongation of PCF. These studies provide a basis for a more uniform and rigorous classification system - a necessary first step towards advancing the field both in investigating aetiology and new intervention strategies.
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Cannon, S. "Female breast cancer : The individual experience and social organisation of its diagnosis and treatment." Thesis, Staffordshire University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384660.
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Jones, Simon Keith. "Mathematical modelling for early detection and treatment of cancer." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241869.
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Swartz, Esti. "Emotional intelligence and locus of control of adult breast cancer patients receiving treatment." Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/d1015686.
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Breast cancer is the most prevalent cancer of women in South Africa, with one in twenty-seven women diagnosed with breast cancer in their lifetime. By building on human strengths, ways can be found to cope effectively with adversity. This will contribute to psychological well-being and result in living constructive and meaningful lives. Emotional intelligence and locus of control are two constructs which, according to previous research, may be associated with psychological wellbeing. Limited research has been conducted on these constructs in populations facing adversity. Adaptation to breast cancer treatment is considered to be an extremely difficult process. The research aimed to explore and describe emotional intelligence and locus of control within an adult breast cancer population. A sample of 67 breast cancer patients receiving treatment was approached to complete a biographical questionnaire and two pencil-and-paper questionnaires. Descriptive and inferential statistics were be used to analyze the data. The results of the quantitative analysis indicated a significant negative correlation between emotional intelligence and locus of control which shows that patients with higher levels of emotional intelligence possess more internal locus of control orientations, while patients with lower emotional intelligence possess more external locus of control orientations. The population presented with above average emotional intelligence and an internal locus of control orientation. The study can be regarded as the first step in opening a field of research which could contribute to more effective coping and the overall psychological well-being of individuals facing adversity in South Africa. Furthermore, the findings of the study contributed to understanding the role of emotional intelligence and locus of control in these populations and encouraged further research and the development and implementation of programmes that promote skills development in these areas.
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Costanzo, Erin Susan. "Post-treatment adjustment and behavior change among women with breast cancer." Diss., University of Iowa, 2006. http://ir.uiowa.edu/etd/56.
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Lawson, Jessica Clair. "Analysis of the anti-cancer activity of novel indigenous algal compounds in breast cancer: towards the development of a model for screening anti-cancer stem cell activity." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1003984.
Full textAbstract:
Breast cancer, the most common malignancy diagnosed in women, is one of the leading causes of death in women worldwide. In South Africa only 32% of women diagnosed with advanced breast cancer survive more than five years. The search for new chemotherapeutic agents capable of effectively treating breast cancer is therefore essential. Recent evidence supporting the cancer stem cell theory of cancer development for breast cancer challenges the current theories of cancer development and hence treatment. Cancer stem cells are a small subpopulation of tumour cells that possess properties of both cancer cells and stem cells and are believed to be the tumour-initiating population of many cancers. Cancer stem cells are inherently resistant to many chemotherapeutic agents and in this way have been associated with repopulation of tumours after chemotherapy. This phenomenon is proposed as a possible mechanism for cancer relapse after treatment. Cancer stem cells have also been implicated in metastasis, the major cause of mortality in cancer patients. Therefore, any treatment that is capable of targeting and removing breast cancer stem cells may have the theoretical potential to effectively treat breast cancer. However, there are currently no such treatments available for clinical use. We were provided access to a library of novel indigenous small molecules isolated from red and brown algae found off the Eastern Cape of South Africa. The aim of this project was to analyse the anti-cancer and anti-cancer stem cell properties of the compounds in this library and to identify „hit‟ compounds which could form the basis for future development into new anti-cancer drugs. Ten novel compounds of algal origin were tested for cytotoxicity, by determining their ability to inhibit the growth of MCF12A breast epithelial cells and MCF7 breast cancer cells using the colorimetric MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assay. All but one of the compounds tested exhibited cytotoxicity towards the MCF7 cancer cell line, with IC50 values (the concentration of the compound that leads to a 50% inhibition in cell growth) of between 3 μM and 90 μM. The chemotherapeutic drug paclitaxel was used as a positive control. Four of the compounds (RUMB-001, RUMB-002, RUMB-007 and RUMB-010/saragaquinoic acid) were significantly more toxic to the MCF7 cancer cell line, than the „normal‟ MCF12A breast cells and were selected as priority compounds for further analyses. In addition, two other compounds were selected as priority compounds, one highly cytotoxic towards both MCF12A and MCF7 cell lines (RUMB-015) and one which was non toxic to either cell line (RUMB-017/018). Preliminary studies into the mechanism of cytotoxicity using Western blot analysis for poly (ADP-ribose) polymerase (PARP) cleavage and Hoechst 33342 immunostaining in MCF-7 cells were largely unsuccessful. The Hoechst 33342 immunostaining assay did provide tentative evidence that selected priority compounds were capable of inducing apoptosis, although these assays will need to be repeated using a less subjective assay to confirm the results. The priority compounds were subsequently investigated for their cytotoxic effect on the cancer stem cell-enriched side population in MCF7 cells. The ability of the priority compounds to selectively target the cancer stem cell containing side population was assessed using two complementary flow cytometry-based techniques – namely the Hoechst 33342-exclusion assay, and fluorescent immunostaining for the expression of the putative cancer stem cell marker, ABCG2+. The ABCG2+ staining assay was a novel technique developed during the course of this study. It remains to be fully validated, but it may provide a new and reliable way to identify and analyse cancer stem cell containing side population cells. The MCF7 cells were treated with the compounds and the proportion of putative cancer stem cells compared with the size of the population in untreated cells was assessed. Three compounds (RUMB-010, RUMB-015 and RUMB-017/018) capable of reducing the proportion of side population cells within the MCF7 cell line were identified. Taking these data together, we identified two potential „hit‟ compounds which should be prioritised for future research. These are compounds RUMB-010/sargaquinoic acid and RUMB-017/018. RUMB-010 is of interest as it was shown to target the putative cancer stem cell population, in addition to the bulk MCF7 tumour line, but was relatively less toxic to the „normal‟ MCF12A cell line. RUMB-017/018 is of interest due to the ability to selectively target the cancer stem cell enriched side population, while having little effect on the normal (MCF12A) or bulk tumour (MCF7) cell lines tested. These compounds will be important as „hit‟ compounds for drug development and as tool compounds to study cancer and cancer stem cell biology.
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Frisk, Jessica. "Acupuncture treatment for hot flushes in women with breast cancer and men with prostate cancer." Doctoral thesis, Linköpings universitet, Obstetrik och gynekologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68806.
Full textAbstract:
Background: The group of women and men with a history of cancer and distressing hot flushes and sweating is growing. The flushes negatively affect Health Related Quality of Life (HRQoL), perhaps partially by disturbing sleep. Treatments that are effective, tolerable and safe need to be developed. There are a number of treatment alternatives that are often not very effective or associated with more or less serious side-effects. Based on theories on the mechanisms behind hot flushes and acupuncture, treatment with acupuncture has been tried in menopausal women with hot flushes and in a few studies in women with breast cancer (BCa). Aim: The general aim of the research leading to this thesis was to evaluate the effect of acupuncture on hot flushes, HRQoL and sleep in men with prostate cancer (PCa) and women with BCa. To evaluate the effect in women with BCa of 12 weeks of electrostimulated acupuncture (EA) and two years of hormone therapy (HT) on number of, and distress caused by, hot flushes, and on HRQoL and sleep. To evaluate whether acupuncture therapy could be used to treat hot flushes in men with PCa treated with castration therapy, and then to evaluate in men with PCa and hot flushes the effect of 12 weeks of traditional acupuncture (TA) or EA on number of, and distress caused by, hot flushes and on urinary excretion of CGRP, HRQoL and sleep. Subjects and methods: Forty-five women with a history of BCa were randomized to oral HT for two years or EA for 12 weeks and were followed up till two years after start of therapy. Thirty-eight men with PCa and hot flushes were treated with acupuncture. Seven men were treated with EA for 10 to 12 weeks in a pilot study. After positive results from this study 31 men were randomized between EA and TA for 12 weeks and followed up till nine months after end of treatment. Hot flushes, HRQoL and sleep were monitored by means of log books and validated questionnaires. Results: The pilot study showed that 10 to 12 weeks of EA in men with PCa reduced number of hot flushes to below 50% of baseline with persistent effects at a follow up three months later. The two randomized studies showed that treatment with acupuncture in women with a history of BCa, and men with PCa was associated with a decrease in both the number of and distress caused by hot flushes by at least 50%. HT almost eliminated the hot flushes. There was no difference in reduction of hot flushes between men receiving EA or TA. Reduction of the number of hot flushes and distress caused by hot flushes probably leads to decreased disturbances at night, and was associated in women with a significant improvement in HRQoL and sleep variables. The improvement in HRQoL was as great in women treated with EA as in women receiving HT although the latter group had a more substantial reduction in number of flushes than the EA group suggesting that EA might have other effects in addition to those on hot flushes. In the men HRQoL did not change significantly. We saw very few and non-serious side-effects in the acupuncture groups and no signs that acupuncture activated the cancer or ovarian/testicular function. Conclusions: Acupuncture reduced the number of hot flushes and distress caused by hot flushes with at least 50% in women and men with hot flushes and a cancer disease and also improved HRQoL and sleep at least in women. Acupuncture should be further evaluated in these patient groups and could be a treatment alternative in patients with troublesome symptoms.
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Blackwelder, Reid B. "Integrative Approaches to Treating Patients with Breast Cancer." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/6985.
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Saarela, A. (Arto). "Diagnosis and surgical treatment of suspicious nonpalpable breast lesions and early breast cancer." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514253604.
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Abstract
The purposes of the present research were to evaluate (1)
the value of ultrasonographically guided fine-needle aspiration
biopsy (US-FNAB) in nonpalpable suspicious breast lesions, (2)
the preoperative use of methylene blue staining in nonpalpable
galactographically suspicious breast lesions, (3) the determinants
of positive histologic margins and residual cancer in wire-guided
biopsy (WGB) of nonpalpable breast cancer and in lumpectomy for
early breast cancer and the determinants of positive radiologic
margins and the correlation between radiologic and histologic margins
and residual disease in WGB of nonpalpable breast cancer, (4) the
assessment of lumpectomy margins by touch preparation cytology
in early breast cancer, and (5) the cosmetic outcome of WGB performed
for benign breast lesions.
The sensitivity and specificity of US-FNAB in 90 nonpalpable
breast lesions were 84% and 93%, respectively.
Preoperative methylene blue staining was successful in 22 out of
30 (73%) cases, making subsequent selective minimal volume
microdochectomy easy to perform. Multivariate analysis of 21 prospectively
evaluated variables was done after 71 WGBs of nonpalpable breast
cancer followed by 54 re-excisions. Large mammographic lesions
had more often positive radiologic margins. Multifocality, large
pathologic size and superficial excision were related to positive histologic
margins and multifocality to residual disease in re-excisions.
The sensitivity and specificity of specimen radiography for predicting
histologic margins were 38% and 81% and those
for residual disease 27% and 79%, respectively.
The corresponding figures for histologic margins in predicting
residual disease were 85% and 59%, respectively.
In a prospective series of 55 consecutive lumpectomies for early
breast cancer, positive histologic margins were found more often in
the presence of intraductal cancer and if the pathologic size of
the index tumor was large. Residual disease was found in 38% of
the cases with positive and in 15% of the cases with negative
histologic margins. A multifocal and nonpalpable index tumor predicted
residual cancer in 34 re-excision specimens. The sensitivity and
specificity of touch preparation cytology in predicting histologic margins
were 38% and 85%, respectively. In WGB, the overall
cosmesis 6 months after surgery was satisfactory in 75 % of
the 101 prospectively evaluated patients with benign proven lesions. Cosmesis
was poorer after deep excisions and complications.
The results indicate that US-FNAB is a useful tool in evaluating
nonpalpable suspicious breast lesions. Preoperative methylene blue
staining crucially facilitates selective minimal volume microdochectomy
in three-quarters of cases. To obtain free margins in WGB, mammographically
and pathologically large lesions should be removed with wider excisions
extending down to the fascia. However, radiologic margins in WGB
and histologic margins both in WGB and in lumpectomy for early
breast cancer may be misleading. Re-excision of the biopsy site
of multifocal tumors after WGB and lumpectomy should be considered.
This is also important after superficial excision in WGB due to
the considerable risk of residual disease. Touch preparation cytology
cannot be recommended for the assessment of margins in lumpectomy
specimens of early breast cancer. Cosmetic outcome after WGB of
benign breast lesions is satisfactory in 75 % of cases.
Deep excisions and complications endanger the cosmetic outcome.
Preoperative biopsy and tumor localization methods have proven
their utility; nevertheless, free margins are still difficult to
obtain and to evaluate accurately. The surgeon may often be forced
to choose between free margins and an acceptable cosmetic outcome.
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Deng, Hou Liang. "Characterizing a novel component of polycomb repressive complex 1 (PRC1) and the functions of CBX6 in breast cancer." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953848.
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Das, Neves Henrique Coutinho Póvoas Esteves. "MCM10, CDT1 and CDC6 as prognostic biomakers and drivers of breast cancer." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953629.
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Antoine, Caroline. "Menopause, breast cancer and menopausal treatments." Doctoral thesis, Universite Libre de Bruxelles, 2018. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/271843.
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RESUME Introduction: Le cancer du sein (CS) est le cancer le plus fréquent chez la femme. Le risque de CS est influencé par de nombreux facteurs. Le traitement hormonal de la ménopause (THM) est l’un d’entre eux. Le risque de CS associé au THM varie probablement en fonction de la population traitée, du type de traitement utilisé, de la durée du traitement et du moment où il est instauré par rapport au début de la ménopause. Il existe des alternatives au THM pour soulager les symptômes de la ménopause. Quelques traitements ont montré une certaine efficacité mais présentent des effets secondaires. D’autres traitements doivent faire l’objet d’études plus approfondies. Objectifs: 1) Contribuer à l’analyse de l’influence du THM sur le CS. 2) Contribuer à l’amélioration de la qualité de vie des patientes ayant eu un CS. Résultats: 1) Nous avons analysé l’évolution de l’incidence du CS et des ventes de THM en Belgique et montré une corrélation entre ces deux paramètres. Nous avons réalisé une revue systématique des études analysant l’association entre l’incidence du CS et l’utilisation de THM. Toutes présentaient des limitations et leur hétérogénéité les rendait difficilement comparables. Nous avons analysé l’évolution des ventes de THM en Europe et montré une diminution importante au cours de la dernière décennie dans l’ensemble des pays étudiés. Nous avons analysé l’évolution de l’incidence du CS et de l’utilisation des THM dans différents pays européens et n’avons pas trouvé d’association entre ces deux paramètres. Nous avons réalisé une revue systématique des études évaluant l’influence du THM sur les caractéristiques du CS et montré que les CS développés sous THM n’étaient pas de meilleur pronostic. 2) Nous avons réalisé deux revues systématiques sur la sécurité d’emploi des THM et des traitements non hormonaux de la ménopause chez les femmes ayant eu un CS. Nous avons montré que le CS représentait une contre-indication au THM et que peu de données existaient concernant les traitements alternatifs. Nous avons mené deux études concernant l’utilisation de traitements de la ménopause chez les femmes ayant eu un CS et montré qu’une proportion importante des femmes ayant eu un CS présentait des symptômes de la ménopause mais que peu d’entre elles utilisaient un traitement. Certains de ces traitements pouvaient potentiellement réduire l’efficacité de leur traitement contre le CS. Conclusions: 1) L’influence exacte du THM sur l’incidence du CS reste difficile à déterminer. D’autres facteurs interviennent également. Nous avons montré l’importance du temps lorsqu’on observe l’évolution de deux paramètres. 2) Les traitements sûrs et efficaces des symptômes de la ménopause chez les femmes ayant eu un CS sont limités. La qualité de vie des patientes ménopausées, ayant souffert d’un CS, peut cependant être nettement améliorée.ABSTRACT Introduction: Breast cancer (BC) is the most common cancer in women. BC risk is influenced by many factors. Menopausal hormone therapy (MHT) is one of them. BC risk associated with MHT may vary depending on the treated population, the type of MHT used, the treatment duration and the delay between the beginning of the treatment and the onset of the menopause. There are alternatives to MHT for the treatment of menopausal symptoms. Some of them have shown some efficacy but have side-effects. Others need further research. Objectives: (1) To contribute to the analysis of the influence of MHT on BC; (2) to contribute to the improvement of the quality of life of BC patients. Results: (1) We analysed changes in BC incidence and MHT sales in Belgium and showed a correlation between these two parameters. We made a systematic review of studies analysing the association between BC incidence and MHT use. All the studies had limitations and were heterogeneous, making them difficult to compare. We analysed changes in MHT sales in Europe and showed an important decrease during the last decade in all the studied countries. We analysed changes in BC incidence and MHT sales in several European countries and found no association between these two parameters. We made a systematic review of studies assessing the influence of MHT on BC characteristics and showed that cases of BC developed under MHT did not have a better prognosis. (2) We made two systematic reviews on the safety of MHT and non-hormonal treatments in BC patients. We showed that BC was a contra-indication to MHT and that few data on alternative treatments were available. We conducted two studies on the use of treatments to alleviate menopausal symptoms in BC patients and showed that an important proportion of these women suffered menopausal symptoms but that few of them were using a treatment. Some of these treatments could reduce the efficacy of their BC treatment. Conclusions: (1) The exact influence of MHT on BC incidence is difficult to evaluate. Other factors are also involved. We showed that long follow-ups are needed when analysing time trends. (2) Efficient and safe treatments for menopausal symptoms in BC patients are limited. However, the quality of life of BC patients may be improved.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
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Ouimet, Lea Ann Maria. "A Quantitative Analysis of Cognitive Impairments Following Breast Cancer Treatment." Thesis, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19769.
Full textAbstract:
One in nine North American women will be diagnosed with breast cancer in their lifetime and most will receive chemotherapy as part of their treatment. Although advances in treatment have increased survivorship, some research suggests chemotherapy results in cognitive deficits in a subset of recipients, a condition known as chemo-fog, thereby compromising quality of life. However, inconsistencies in methodology and neuropsychological assessment have complicated comparison of findings. The first objective of this thesis was to review the methodological issues with an emphasis on the quantitative techniques typically employed. A comparison of group and individual based analyses found negligible effects for both univariate and multivariate approaches while individual based analyses identified severe declines in function in a subset of participants. A standardized-regression based (SRB) approach was recommended as the method of choice. Furthermore, it was recommended that the number of tests be limited since comprehensive batteries can complicate identification due to increased risk of misclassification. Therefore, the second goal of the thesis was to evaluate the sensitivity of a reduced battery to the declines associated with chemo-fog. A comprehensive neuropsychological battery comprising 23 tests was compared to a subset of nine tests. SRB analyses demonstrated that a more selective battery was equally useful and may be appropriate for identification of chemo-fog. Given the variability in the composition of neuropsychological test batteries, the final aim of this thesis was to compare the structure of the theoretical cognitive domains with ones identified through exploratory factor analyses (principle axis factoring) to evaluate the convergence between the two. The results demonstrated there is statistical support for the conceptual framework that underlies the composition of the domains. The contributions of this thesis include providing methodological guidelines for those conducting future research in this area to ensure that results are comparable across studies and are meaningful, and evaluating the utility of a screening battery to facilitate identification of chemo-fog. In addition, it was demonstrated that despite the lack of professional guidelines informing the selection and construction of neuropsychological test batteries, there is statistical evidence to support the practice of grouping tests into domains based on theoretical grounds.
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Abedin, Farhana. "Magnetic and albumin targeted drug delivery for breast cancer treatment." Thesis, Wichita State University, 2011. http://hdl.handle.net/10057/5054.
Full textAbstract:
This research work involves multifunctional magnetically targeted drug delivery
microspheres for treatment against breast cancer. A combination therapy approach was followed
by encapsulating two chemotherapeutics, 5-Fluorouracil (5-Fu) and cyclophosphamide in
poly(D, L-lactide-co-glycolide) (PLGA) microspheres. Magnetite nanoparticles and albumin
were also incorporated in the microspheres to achieve targeted treatment. The microspheres were
fabricated using oil-in-oil emulsion/solvent evaporation technique. Albumin is attracted to cancer
cells and thus it is likely to draw the microspheres towards tumor cells. On application of
magnetic field near tumor site, magnetites in the microspheres are likely to guide them to the
region of magnetic field. This will allow release of drugs from microspheres in the cancer cells.
Also the burst release of drugs and then slow release due to diffusion in the cancer cells lead to
effective treatment and also limit excessive spreading of drugs in other regions of the body.
Release rate study was carried out using high performance liquid chromatography (HPLC). Invitro
and in-vivo study was carried out to check the efficacy of treatment.Thesis (M.S.)--Wichita State University, College of Engineering, Dept. of Mechanical Engineering.
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Lambe, Camille Eckerd Germino Barbara B. "Complementary and alternative therapy use during treatment of breast cancer." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,671.
Full textAbstract:
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Nursing." Discipline: Nursing; Department/School: Nursing.
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Sulaiman, Andrew. "New Approaches for the Treatment of Triple Negative Breast Cancer." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39100.
Full textAbstract:
Triple‐negative breast cancer (TNBC) is the most refractory subtype of breast cancer to current treatments and accounts disproportionately for the majority of breast cancer‐related deaths. Research has not yet identified specific therapies for TNBC and chemotherapy remains the conventional therapy in the clinic. While conventional chemotherapy regimens have demonstrated success at reducing bulk tumor burden, they have been shown to enrich cancer stem cells (CSCs). CSCs promote chemoresistance, metastasis, heterogeneous tumor regeneration and disease relapse. Owing to tumor plasticity and the conversion between CSC and non-CSC subpopulations development of a strategy capable of inhibiting both non-CSC and CSC subpopulations is crucial for TNBC therapy. In this compilation of my main research projects, several new approaches for the treatment of TNBC were identified which target not only the bulk tumor population but also the CSC populations residing within the tumor:
1. Co-suppression of Wnt, HDAC, and ESR1 using clinically relevant low‐dose inhibitors effectively repressed both bulk and CSC subpopulations and converted CSCs to non‐CSCs in TNBC cells.
2. Co-inhibition of mTORC1, HDAC, and ESR1 was capable of reducing both bulk and CSC subpopulations as well as the conversion of fractionated non-CSC to CSCs in in a human TNBC xenograft model and hampered tumorigenesis following treatment.
3. Inhibition of Wnt and YAP retarded tumor growth of TNBC cells in either epithelial or mesenchymal states, and both CD44high/CD24low and ALDH+ CSC subpopulations were diminished in a human xenograft model reducing tumorigenicity following treatment.
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Silva, Andreia M. "Investigating c-FLIP suppression and TRAIL treatment in breast cancer." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/110419/.
Full textAbstract:
Breast cancer mortality is invariably due to metastasis, the dissemination of cancer cells from the primary tumour to distant organs. This process is proposed to arise from the breast cancer stem cells (bCSCs), the minority of cells within a tumour that are capable of propagating new tumour growth. bCSCs are also associated with potentiating endocrine therapy resistance and therefore relapse after tamoxifen or anastrozole treatments. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is an anti-cancer agent that induces apoptosis in bCSCs and has almost no toxicity to normal cells. However, there is an inherent resistance to TRAIL in vitro in a large proportion of breast cancer cell types due to the expression of the survival factor cellular FLICE-Like Inhibitory Protein (c-FLIP). It has been shown that siRNA-mediated suppression of the gene for c-FLIP combined with TRAIL is effective in vitro at sensitising bCSCs to apoptosis in breast cancer cell lines. To test whether these findings have direct clinical relevance for breast cancer patients, diagnostic biopsies, surgical breast resections and pleural effusions were collected from the clinic. Testing TRAIL alone in breast samples resulted in a decrease in the number of tumourspheres in 82% of tumours that have acquired endocrine resistance to tamoxifen and anastrozole. Importantly, TRAIL was efficient in vivo at decreasing primary tumour size in tumours that have acquired resistance to tamoxifen in vivo and number of metastases of an anastrozole-resistant sample. Additionally, TRAIL was also effective at decreasing bCSCs in triple negative metastatic tumours, corroborating studies supporting a relationship between a mesenchymal phenotype and TRAIL sensitivity. However, there was no correlation between TRAIL response and either ER or HER2 status in primary breast samples. Furthermore, c-FLIP was suppressed, either genetically (siRNA) or pharmacologically (OH14) and combined with TRAIL treatment sensitised bulk and bCSCs to TRAIL in breast tumours from patients with metastatic disease irrespective of their estrogen receptor (ER)/HER2 status. As the tumour microenvironment can modulate drug responses, TRAIL treatment was investigated on breast cancer epithelial cells in the presence of cancer associated fibroblasts (CAFs) and CAFs-conditioned medium (CM). Short exposure to CAFs and CM sensitised MCF-7 and primary metastatic cells to TRAIL whereas a longer exposure to CM conferred resistance to TRAIL potentially due to an induction of epithelial-mesenchymal transition. With these results in primary cells, TRAIL could be a valuable treatment to the clinic for patients that have acquired resistance to endocrine treatments. Additionally, c-FLIP suppression and TRAIL treatment could be a promising therapeutic treatment at eliminating bCSCs in patients with metastatic disease. We hypothesise that a partial EMT confers resistance to TRAIL but a full EMT state is associated with resistance to TRAIL.
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Chilewski, Shannon D. "Development of CAPER Peptides for the Treatment of Breast Cancer." Thesis, University of the Sciences in Philadelphia, 2020. http://pqdtopen.proquest.com/#viewpdf?dispub=27547515.
Full textAbstract:
Breast cancer is a leading cancer among women and is a major cause of death worldwide. While not just one disease, breast cancer encompasses many biologically different subtypes with distinct pathologies and clinical ramifications. In the case of estrogen receptor (ER) positive breast cancer, estrogens stimulate mammary epithelial cell proliferation and contribute to the development and progression of the disease. To treat ER-positive breast cancer patients, endocrine targeted therapies such as tamoxifen are commonly used. However, 40–50% of these patients do not respond or develop resistance to these therapies, and therefore additional treatment options are needed. In the case of triple negative breast cancer (TNBC), there is a lack of expression of the ER, progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) and this subtype has the poorest prognosis. There are currently very limited therapies available for TNBC, and due to the receptor status, endocrine therapies are ineffective. This leaves TNBC patients with chemotherapy and radiation as the only options, and therefore additional treatments are urgently needed. CAPER is a coactivator of activating protein-1 (AP-1) (interacting specifically with the c-Jun component) and the ER and is known to be involved in human breast cancer pathogenesis. Not only has CAPER shown a role in ER-positive breast cancer but recent data has also demonstrated a role for CAPER in TNBC. In normal breast tissue, CAPER is not detectable or expressed at low levels. However, in both ER-positive and TNBC, CAPER exhibits a significantly higher level of expression. Additionally, it has been shown that when CAPER expression is reduced via knockdown cell proliferation is decreased in both in vitro and in vivo settings. Due to CAPER’s role in both ER-positive and TNBC, disrupting the interaction of CAPER with the ER and/ or c-Jun could be a novel approach to treat breast cancer patients. The work described herein will review the development and in vitro testing of CAPER peptides to inhibit the coactivator activity of CAPER with c-Jun and/or the ER.
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Azadbakht, Narges. "Stromal and epithelial changes in breast cancer following endocrine treatment." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/stromal-and-epithelial-changes-in-breast-cancer-following-endocrine-treatment(c6542eba-83e2-48de-a566-8f5eccd9a7b1).html.
Full textAbstract:
Anti-oestrogens and aromatase inhibitors are currently used as endocrine therapies in breast cancer. Despite the significant role that these treatments play in reducing breast cancer mortality, some patients may display intrinsic and acquired therapeutic resistance. Different mechanisms are thought to contribute to endocrine resistance in patients treated with anti-oestrogens such as tamoxifen and aromatase inhibitors such as letrozole. The importance of epithelial-stromal interactions in progression of breast tumour and the potential contribution of these interactions in resistance to tamoxifen have been suggested using data from different studies. Stromal compartment has also been shown to exhibit possible prognostic and therapeutic significance in breast cancer. Therefore it is essential to acquire better understanding of the changes in stromal and epithelial cells that occur during successful and unsuccessful endocrine treatment. In this study an important trial in which patients received tamoxifen for short windows was under investigation. Biopsies were taken from these patients before and after treatment. These biopsies were available as formalin-fixed paraffin-embedded (FFPE) tissue blocks. Responding and non-responding patients were identified according to the Ki67 scores. Laser Capture Microdissection (LCM) was utilised to microdissect epithelial and stromal cells from the biopsies taken after treatment. The samples obtained following microdissection underwent RNA extraction and were subsequently used for gene expression profiling. Several differentially expressed genes in the epithelial and stromal compartments of tamoxifen responding and non-responding cases were identified. To assess the significance of the differentially expressed genes between the non-responding and responding cases, bioinformatics approaches were employed to incorporate the acquired data into functional enrichment analysis, pathway analysis and network construction. To examine the presence of possible predictive markers for therapeutic response and potential targets for therapy in breast cancer within the differentially expressed genes, data was compared to several published gene sets and publicly available datasets. Several significant genes involved in recognised pathways and networks were identified within the list of differentially expressed genes. The presence of previously proposed possible markers within the differentially expressed genes was also confirmed. These findings can be further explored for the future management of breast cancer.
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Modi, Stephanie. "Lymphatic function in the arm following treatment for breast cancer." Thesis, St George's, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486357.
Full textAbstract:
Aims. The primary aim was to quantify changes in ann lymphatic function after axillary treatment for breast cancer. The hypotheses tested were that [1] impairment ofmuscle lymph drainage after axillary surgery precedes the onset of overt subcutaneous breast cancer related lymphoedema (BCRL); [2] regionality ofswelling in BCRL is due to . local regional impairment oflymph drainage; [3] the force oflymphatic collector pumping is weakened by the chronically raised afterload in BCRL anns. Methods. The removal rate constant, k, was used to measure local lymph drainage of 99mTc-HIG injected jnto the subcutis and muscle. Lymphatic collector pump force (Ppump) was assessed using a novellymphoscintigraphic method based on the escape of distally injected 99mTc-HIG under a pressurised upper ann cuff. Principal results. (i) No pre-BCRL reduction was found in kmusc/e (or ksubcutis) 7 months after surgery (ii) kwas faster in both anns ofnon-BCRL patients destined to develop BCRL compared with those who did not develop BCRL (ksubcutis by 37%, n =7, p = 0.0008; kmusc/e by 23%, P =0.035, n =7) (iii) In non-BCRL and mild BCRL anns kmusc/e was 2-3 fold faster than ksubcutis (p« 0.001, n ~ 26) (iv) ksubcutis was not significantly lower at sites ofmaximal swelling than minimal swelling in BCRL anns (v) proximal ksubcutis was 26 % faster than distal ksubcutiS (p = 0.02, n = 11) and correlated positively with ann circumference (r =0.32, p = 0.03, n = 44) irrespective ofBCRL (vi) P pump was reduced by 38% in BCRL anns relative to healthy anns (p = 0.014, n = 16 ofeach) and correlated negatively with foreann swelling (r =0.22, p = 0.011, n = 16). Conclusions. Non-BCRL patients with higher capillary filtration rates had an increased risk ofdeveloping BCRL. Weakening ofPpump was a factor contributing to BCRL. Proximal foreann subcutis lymph drainage was greater than in the distal foreann regardless of swelling, possibly due to faster muscle than subcutis lymph flow.
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Conway, Brianna. "Searching for Synergy: FAK Inhibition in Metastatic Breast Cancer Treatment." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37304.
Full textAbstract:
Breast cancer is the most common cancer among Canadian women and 14-20% will develop lethal metastases within 5 years. A potential novel therapeutic target is Focal Adhesion Kinase (FAK), a cytoplasmic tyrosine kinase. FAK’s expression is inversely correlated with survival and is known to regulate cell migration, proliferation and invasion. While tyrosine kinase inhibitors are historically ineffective as single agents, they are commonly used as part of combination therapies.
Therefore, given its central role in tumor cell biology and cell signaling, we hypothesized that inhibiting FAK in combination with pharmacological agents commonly used to treat metastatic breast cancer patients will result in enhanced anti-tumor activity.
We combined a commercial FAK inhibitor (PF-562271) with a range of chemotherapeutic agents commonly used to treat metastatic breast cancer and searched for synergistic partners. Only DNA topoisomerase inhibitors showed potential to synergistically reduce cell viability when paired with low doses of the FAK inhibitor.
However, the combination does not induce an increase in cell death or apoptosis. It was then discovered that both agents in isolation and in combination produce increased levels of ROS, a toxic metabolite. This, along with other more preliminary data, provides clues for a novel proposed mechanism of action for this interaction.
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Johansson, David. "Bacterial toxins for cancer treatment." Doctoral thesis, Umeå universitet, Medicinsk biovetenskap, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1637.
Full textAbstract:
Even though anti‐cancer chemotherapy has been continuously improved during the last decades. problems with adverse effects and drug resistance still constitutes a considerable obstacle and sets a demand for new effective treatment options. Tissue homeostasis in multi‐cellular organisms is maintained through intrinsic cell death, apoptosis, which removes unwanted or damaged cells. Disrupted apoptosis is an important factor in tumorgenesis and drug resistance, therefore induction or restoration of apoptotic pathways is also important for the treatment of cancer. Several naturally occurring bacterial toxins have the ability to induce apoptosis and could thus be candidates to complement or improve the therapeutic effect of other anticancer drugs. The bacterial toxins, adenylate cyclase (AC) toxin from Bordetella pertussis, α‐toxin from Staphylococcus aureus and verotoxin‐1 (VT‐1) from Escherichia coli were investigated for their ability to induce apoptosis in different tumor cell lines. Toxin induction of cell death was investigated by cell viability assays, end‐stage apoptosis induction by DNA‐fregmentation (TUNEL) assay. Toxin receptor expression and signal transduction pathways to apoptosis were investigated by flow cytometry, caspase enzyme activity assays and western blot. Immunohistochemistry was used for identification of toxin receptor expression in tumor tissue samples. AC‐toxin was cytotoxic and induced apoptosis in cultured malignant plural mesothelioma (MPM) and small‐cell lung cancer (SCLC) cells. Low‐toxic concentrations of AC‐toxin enhanced cisplatin cytotoxicity and apoptosis in both cell lines. MPM‐cells with acquired cisplatin resistance were more sensitive to α‐toxin than the less resistant parental MPM cell line. A low‐toxic concentration of α‐toxin re‐sensitized resistant MPM cells to cisplatin cytotoxicity by apoptosis induced through the mitochondrial pathway without detectable activation of common up‐stream apoptosis signalling proteins. VT‐1 was highly cytotoxic and induced apoptosis in globotriosylceramide (Gb3) ‐expressing glioma, breast cancer and non‐small‐cell lung cancer (NSCLC) cells but was not cytotoxic to non‐Gb3‐expressing cells. PPMP, an inhibitor of glucosylceramide synthesis which makes exposed cells unable to synthesize Gb3 rendered Gb3‐expressing cells resistant to VT‐1. MPM cells with acquired‐cisplatin resistance expressed Gb3 in contrast to the absent of expression in the less resistant parental cell line. Gb3, could however be up‐regulated by cisplatin in Gb3‐negative MPM‐cells. Presence of a low‐toxic concentration of VT‐1 potentiated cisplatin‐induced cytotoxicity and apoptosis in the cisplatin‐resistance MPM cell line. VT‐1 was a potent inducer of apoptosis, probably via stress‐induced Mitogen‐activated protein kinase (MAPK)‐signaling involving c‐Jun N‐terminal kinase (JNK) and p38, leading to disruption of the mitochondrial membrane integrety, activation of caspase‐9 and ‐3, and ultimately DNA fragmentation and cell death. Gb3 expression was demonstrated in clinical specimens of glioblastoma and breast cancer making these tumor types interesting for further VT‐1 studies. We conclude that bacterial toxins may be used to induce apoptosis in several types of cancer cells. Low concentrations of verotoxin‐1 and α‐toxin may potentially be used to overcome acquired cisplatin‐resistance in cancer patients.
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Reed, Alyssa, and University of Lethbridge Faculty of Arts and Science. "Variation in waiting times from diagnosis to treatment for breast cancer patients in Alberta from 1997-2000." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2003, 2003. http://hdl.handle.net/10133/196.
Full textAbstract:
There is considerable evidence that delays in diagnosing and treating breast cancer reduce long-term survival. The purpose of this study was to assess the waiting time between diagnosis and treatment for Alberta women with breast cancer and to examine the influence of age, cancer stage, Regional Health Authority (RHA), community size, and year of diagnosis on this time interval. The data were obtained from the Alberta Cancer Board. The information included approximately all Alberta women with breast cancer between 1997 and 2000. The overall median waiting time was 17 days. The mean and median delay increased by an average of two days each year. Only 43.8% of cases were treated within the recommended 14 days. The delay was significantly longer for women younger than 70, with stage 1 disease and from Northern RHAs. Efforts must be made to decrease delay and ensure that all women receive equal access to health services.xii, 106 leaves : ill. ; 28 cm.