Дисертації: "Cancer (colorectal, breast, cervical)"

1

Valášková, Veronika. "EFEKTIVITA SCREENINGOVÝCH PROGRAMŮ ZHOUBNÝCH NÁDORŮ V ČESKÉ REPUBLICE." Master's thesis, Vysoká škola ekonomická v Praze, 2015. http://www.nusl.cz/ntk/nusl-194341.

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This diploma thesis deals with the national screening programs for cancer diagnosis. The goal of this thesis is to find a proper way how to evaluate the effectivity of screening programs as well as their influence on the intensity of mortality from certain types of cancer. For the purpose of finding out necessary information were used data related to the diagnosis of colorectal cancer, a diagnosis of cervical cancer and breast cancer in the population of the Czech Republic between 1977 - 2011. This thesis is divided into eight chapters. The first chapter is an introduction to the topic and contains the description of the main goals. The second chapter defines terms that are crucial for this thesis. The third chapter is devoted to data sources and institutions that collect different types of data and health statistics. The next chapter deals with the epidemiology of all described types of cancer and also provide information on risk factors and symptoms of the disease. The fifth chapter looks back at trends in mortality and incidence of the most common malignant tumors in the Czech Republic. The sixth chapter describes planning and implementation of screening processes. The seventh history of screening programs in the Czech Republic. The eighth chapter deals with the rules and regulations of the EU Council and the World Health Organization. The ninth chapter represents the final assessment of Czech screening programs, compared both to the WHO guidelines and the results in the world. The last chapter is including description of mortality and their reaction on screening programs. Text describes even comparison with two other European countries (Germany, France).

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2

Green, Margaret. "Prognostic factors in breast and colorectal cancer." Thesis, University of Surrey, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298045.

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3

Hanson, Jon. "Mucin expression in breast cancer colorectal cancer and adenomatous polyps." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251293.

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4

El-Baruni, Khaled S. "Factor X-activating activity in breast and colorectal cancer." Thesis, University of Southampton, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293698.

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5

Kan, Chin-Yi. "Human Papillomavirus in human breast cancer and cellular immortalisation." Sydney : University of New South Wales. Biotechnology and Biomolecular Sciences, 2007. http://www.library.unsw.edu.au/~thesis/adt-NUN/public/adt-NUN20071004.080541/.

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6

Gornall, Robert J. "TP53 polymorphisms and haplotypes in breast, cervical and ovarian cancer." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310562.

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7

Wolstenholme, Jane. "Counting the costs of cancer care : breast, cervical and lung cancer in Trent." Thesis, University of Nottingham, 2001. http://eprints.nottingham.ac.uk/12097/.

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The purpose of this thesis is to explore the theory, practice and application of costing with specific reference to cancer. In part it reviews the theory and guidelines related to costing methods including the recent focus on the analytical techniques used with cost data. In addition it examines how these theories and guidelines are applied in practice, by reviewing the literature on costs and cancer. The empirical research in this thesis applies costing methods to three specific cancer sites; breast, cervix and lung. This analysis provides information on the total burden of these specified cancers in terms of cost to a typical health authority (Trent). It also explores the hypothesis highlighted in previous studies that the cost of cancer increases with the stage of the disease. The final area of contribution for the thesis is in the application of recently suggested analytical techniques for cost data to the breast, cervical and lung cancer data sets; it investigates a number of proposed techniques for the analysis of skewed cost data and methods for data with incomplete patient follow up.

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8

MacKenzie, Naomi. "Quality of life following surgery for breast and colorectal cancer." Thesis, University of Central Lancashire, 2004. http://clok.uclan.ac.uk/20514/.

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Background. Colorectal and breast cancers are two of the commonest malignant diseases. The approach to these two cancers is markedly different with patients suffering from breast cancer having the benefits of screening, specialist nurses and support groups. In contrast, colorectal cancer has received less attention in terms of screening, support and public interest. Purpose. This study aimed to collect prospective data on presentation, predisposing factors, co-existing morbidity and management of patients with breast and colorectal cancer and make comparisons with national guidelines. It examined patient perceived quality of life in both colorectal and breast cancer groups prior to and following surgery. The groups were further divided by gender and into stoma and non-stoma (colorectal cancer) and mastectomy and breast conserving surgery (breast cancer). In addition, the work compared the life quality between the colorectal and breast cancer groups and evaluated the appropriateness of newly developed disease specific QOL questionnaires on a UK population. Methods. This study formed a prospective longitudinal repeated measures design. Patients were evaluated at three time points over a six month period starting at the time at which they underwent their cancer surgery. At the first assessment demographic, clinical and QOL data were collected and at 3 and 6 months clinical data was updated and QOL assessed. Clinical data consisted of pathology, adjuvant therapy, morbidity and mortality. QOL was measured at each assessment using the generic cancer EORTC QLQ-C30 instrument. In addition, the colorectal specific module (EORTC QLQ-CR38) and the breast specific module (EORTC QLQ-BR23) were administered at 3 and 6 months post surgery. Results. The clinical data was compared with national guidelines for each cancer population. Guidelines for colorectal cancer were not followed closely whereas those for breast cancer were more formally adhered to. Over the study period, patients with colorectal cancer reported an improvement in emotional functioning, gastrointestinal (CI) symptoms, pain and weight gain. Males reported more nausea, vomiting, dyspnoea and pain. They also had greater sexual enjoyment, although reported more sexual problems. The stoma group had decreased social functioning throughout the study, increased 31 symptoms and sexual problems at 3 months. The non-stoma group had increased emotional functioning from surgery to 3 months and improved sleep. Over the study period, patients with breast cancer reported deterioration in pain, fatigue, dyspnoea and sexual enjoyment. Additionally, at 3 months they reported poorer physical functioning, role functioning and social functioning. The breast conserving group reported deterioration in cognitive functioning, emotional functioning and global well-being and worse diarrhoea. The mastectomy group reported better physical functioning, but poorer role functioning, body image and future perspective. A comparison of the two cancer groups indicated that there were few QOL differences. The colorectal cancer group had worse pain at the time of surgery and reported more 31 symptoms throughout the study. The breast cancer group had better social functioning, role functioning and physical functioning at the time of surgery, but complained of worse pain at 3 months and had poorer emotional functioning throughout the study. It is interesting to note that for both cancer groups there were generally high levels of functioning. There was difficulty in interpreting some of the data because the questionnaires were not appropriate/sensitive in certain areas for these populations. There were many missing answers to the questions on sexual health. Conclusions. This work has provided an insight into the management of two common cancers at a time when guidelines were being established. Quality of life measures with greater sensitivity are required so that they can be used in all clinical trials and longitudinal studies to provide comparable information. There is a need to generate meaningful QOL data that can be easily understood by all clinicians involved in cancer care and which can be incorporated into clinical management.

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9

Wiseman, Kara P. "Improving Understanding of Colorectal Cancer Screening Decisional Conflict and Breast Cancer Survivorship Care." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3774.

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Background: Behavioral interventions and evidence based guidelines along the cancer control continuum can reduce the burden of cancer. Objectives: This dissertation aims to increase our understanding of colorectal cancer screening (CRCS) decisional conflict and breast cancer survivorship care. This project: 1) assesses CRCS decisional conflict in a general population, 2) uses the Theory of Triadic Influence to model and evaluate direct and indirect associations between CRCS decisional conflict and colonoscopy adherence, 3) assesses post-treatment breast cancer care. Methods: Data from a questionnaire administered to randomly selected adults, 50-75 years, living in six MN communities (N=1,268) and the 2010 Behavioral Risk Factor Surveillance System (BRFSS) (N=1,024, women ages 27-99) were used. Multivariable logistic regression was used to identify characteristics associated with high CRCS decisional conflict; then structural equation modelling (SEM) was performed to assess direct and indirect associations of CRCS decisional conflict and colonoscopy adherence. Using BRFSS data, multivariable logistic regression was performed to assess the association between years since diagnosis and the type of clinician providing the majority of care for breast cancer survivors after treatment completion. Results: Greater colonoscopy barriers (OR=1.04; 95% CI: 1.02-1.05) and CRCS-specific confusion (OR=1.12; 95% CI: 1.10-1.15) as well as a healthcare provider not discussing CRCS options (OR=1.67; 95% CI: 1.18-2.37) were associated with increased odds of high CRCS decisional conflict. A similar relationship was found in the SEM analyses: both greater levels of perceived colonoscopy barriers and CRCS confusion were associated with higher decisional conflict (standardized total effects=0.42 and 0.39, respectively, p-values < 0.01). CRCS decisional conflict was associated with increased non-adherence to colonoscopy. This relationship was mediated by CRCS-specific self-efficacy and intention (standardized total effect=0.14, p-value <0.01). Among breast cancer survivors, women 0–1 and 2–3 years since diagnosis were 2.1-2.6 times more likely to have a cancer-related clinician providing the majority of care compared to women 6+ years since diagnosis (95% CIs: 1.0-4.3; 1.4-4.6). Conclusions: Decreasing colonoscopy barriers and CRCS-specific confusion could decrease CRCS decisional conflict and ultimately increase CRCS uptake. National policies to move breast cancer follow-up care to a primary care provider might be well-received by cancer survivors.

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10

OKAMOTO, TOMOMITSU, SHIGEKO SAITO, SHIHO TANAKA, SACHI NAGAI, YUKIKO MORI, and MAI HORIKAWA. "METASTATIC BREAST CANCER TO THE UTERINE CERVIX MIMICKING A GIANT CERVICAL LEIOMYOMA." Nagoya University School of Medicine, 2012. http://hdl.handle.net/2237/16745.

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11

Collier, Ashley. "Integration of family health history in clinical guidelines for breast, ovarian, and colorectal cancer." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337350837.

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12

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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13

Bety, Santa. "Comparison between the Swedish healthcare regions regarding the use of different cancer medications : - breast cancer, colorectal cancer and gastric cancer." Thesis, Uppsala universitet, Institutionen för farmaci, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-439964.

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INTRODUCTION: Gastrointestinal cancers are one of the most fatal malignancies worldwide in both genders and all ages while breast cancer is the leading cause of cancer deaths in women internationally. Angiogenesis inhibitors and epidermal growth factor inhibitors are mainly used in colorectal and gastric cancer, while cyclin-dependent kinase inhibitors are mainly used in the treatment of breast cancer. However, studies of cost-effectiveness are needed to assess whether the high prices for these drugs can be justified with better outcomes and to what extent the total expenditure is acceptable for the health care system. Regional comparisons are important for future advancement within the field. PURPOSE: The aim with this study was to describe whether there were any differences regarding the use of selected cancer drugs in Sweden’s six healthcare regions from 2005 to 2020. METHOD: This research was a descriptive-comparative study. The aggregate-level data used in this paper was provided by the Swedish eHealth Agency and included the measurement total sales cost per 100,000 inhabitants of cyclin-dependent kinase inhibitors for both outpatient care as well as inpatient care. The angiogenesis inhibitors and epidermal growth factor receptor inhibitors were solely used in inpatient care. All data included both genders and all ages. RESULTS: The majority of the cancer drugs studied in this paper had an uneven use and major differences were noted between the regions as regards the consumption of specifically bevacizumab and palbociclib in all the healthcare regions. Notable was the uptake of bevacizumab with approximately a four-fold difference between the southeast healthcare region and the west healthcare region in the year 2020. Palbociclib demonstrated circa seven-fold difference in uptake in the year 2020 between the west healthcare region and the north healthcare region. CONCLUSION: Broadly, we can conclude that there are regional differences in the use of angiogenesis inhibitors and epidermal growth factor inhibitors in the treatment of colorectal cancer and gastric cancer. Cyclin-dependent kinase inhibitors also demonstrate regional differences in the treatment of breast cancer in Sweden’s six healthcare regions. It is of interest to further study why the regional differences exist in Sweden.

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14

Kelly, Barry Eoin. "The value of duplex sonography in the management of colorectal and breast cancer." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263323.

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15

Ljuslinder, Ingrid. "Studies of LRIG1 and the ERBB receptor family in breast and colorectal cancer." Doctoral thesis, Umeå : Umeå university, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-25678.

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16

IORIO, JESSICA. "Networking of ion channels with metabolism-related membrane transporters during colorectal and breast cancer progression." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1072448.

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Ion Channels and Transporters (ICTs) are progressively emerging as a novel class of membrane proteins expressed in several types of human cancers and regulating the different aspects of cancer cell behavior. One of the ion channels dysregulated in cancers is hERG1 potassium channel and we investigated the role of hERG1 and other ICTs in colorectal and breast cancer. We started with the analysis of a pro-angiogenic signalling pathway involving hERG1 and β1-integrin (reported earlier in vitro) in primary samples from mCRCa (metastatic Colorectal Cancer) patients treated with Bevacizumab (BV). We found that this pro-angiogenic pathway interacts also in mCRC patients and that hERG1 is a positive prognostic biomarker for mCRCa patients treated with BV. Then we studied the role of hERG1 and Kca3.1 potassium channels in pH regulation mechanisms in colorectal cancer cells. It emerged that there is a cross talk among β1-integrins, hERG1, Kca3.1 and sodium-hydrogen exchanger 1 (NHE1) in cells and primary samples of CRCa. So we started to investigate the expression of hERG1, Kca3.1 and NHE1 in breast cancer. For the first time, hERG1 expression was found in primary breast cancer tissues and it emerged that hERG1 expression is associated with molecular subtype group. Since the nNaV1.5 channel has a principle role in breast tumor progression and we found that hERG1 is expressed in breast cancer tissues and in vitro data demonstrated that there is a networking between hERG1 and nNaV1.5 channels, we performed analysis for nNaV1.5. We found that hERG1 and nNaV1.5 are expressed in primary breast cancer samples and they are positively associated. It occured particulary in Basal Like/triple negative samples and the co-expression was found in the some tumor cells. These data encourage us to develop a monoclonal antibody (mAb) capable to recognise the nNaV1.5 channel. Thus 24 mAb clones were produced and screened and we validated putative mAbs and isolated one mAb with promising high specificity for nNaV1.5, with significant oncological therapeutic potential.

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17

Batarfi, Nahid. "Saudi women's experiences, barriers, and facilitators when accessing breast and cervical cancer screening services." Thesis, University of York, 2012. http://etheses.whiterose.ac.uk/7558/.

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Background: Breast cancer is considered the most common cancer among females followed by cancers of the cervix, lung, and stomach. Its mortality can be avoided by early detection. Aim: This thesis aimed to explore Saudi women’s barriers facilitators and experiences, when accessing breast and cervical cancer screening services in the United Kingdom (UK) and Saudi Arabia. Methods: A mixed method approach was used to fulfil the thesis objectives. A quantitative questionnaire was administered to 503 Saudi women living in the United Kingdom and in Kingdom of Saudi Arabia. This was followed up by a qualitative study using seven focus groups discussions. Results: Survey and focus groups provided some consistent findings regarding Saudi women’s perceptions, knowledge, beliefs of the barriers and facilitators in accessing both breast and cervical cancer screening services in the UK and Saudi Arabia. Fear of having cancer and lack of knowledge of the importance of early detection, particularly in cervical cancer were major findings with regard to barriers to attend screening services. However, being employed and highly educated was correlated with better knowledge and awareness of the signs, symptoms, and treatment of both breast and cervical cancer. Participants shared their responsibilities with health professionals and the structure of the health system in the arrangement of early screening of breast and cervical cancers. Additionally, they suggested the role of media, education, and use of places such as mosques in disseminating information about the importance of early cancer detection. Conclusion: While the data reported in this thesis are encouraging, rich and diverse, conclusions must be drawn with caution. Important barriers included health and cultural beliefs and attitudes, language and unsupportive attitudes of health professionals. A majority of Saudi participants believed educational programs would increase breast and cervical cancer awareness and knowledge and use of screening services. The health belief model was utilized to structure and explain the thesis findings and analysis.

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18

Lai, Man Po. "Single nucleotide polymorphisms of CYP2C19 gene and AHR gene and their associations to colorectal cancer and breast cancer risk in Han Chinese population /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202007%20LAI.

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19

Nuño, Thomas. "Breast and Cervical Cancer Screening Patterns among Rural Hispanic and American Indian Women in Arizona." Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/202518.

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Breast and cervical cancer disparities among Hispanic and American Indian women are a significant public health problem. Breast cancer is the most common neoplasm among Hispanic women. Cervical cancer has a higher incidence and mortality among Hispanic women compared to non-Hispanic White women. Breast cancer detection often comes late for American Indian women and breast cancer survival for this population is relatively poor. Hispanic and American Indian women who reside in rural areas of Arizona are especially at-risk of non-participation in breast and cervical cancer screening programs. This dissertation utilized data from two sources: a health-education intervention trial designed to increase mammography screening among women living in a rural area along the U.S.-Mexico border of Arizona and survey data from multiple years of the Arizona Behavioral Risk Factor Survey (BRFS) focusing on breast and cervical cancer screening self-reported behaviors. The purpose of the dissertation research was to identify factors associated with cancer screening behaviors among Hispanic and American Indian women that reside in rural Arizona settings. Hispanic women who participated in the promotora-based educational intervention program were more likely to report receiving a mammogram at the followup compared to women who did not participate in the program. Results from both the baseline community survey and the BRFS showed that Hispanic women who received prior recommendations from a clinician to get both mammography and Pap smear were more likely to report they received a mammogram within the past year and a Pap smear within the past three years. Rural Hispanic and American Indian women reported lower rates of ever having had breast and cervical cancer screening compared to their urban counterparts. Breast and cervical cancer screening use in these populations can potentially be increased with at least two strategies. First, clinician recommendation of both mammograms and Pap smears and opportunistic screening during regular clinic visits may increase breast and cervical cancer screening coverage. Secondly, culturallyappropriate interventions that utilize promotoras or lay health advisors could increase screening rates. In conclusion, Hispanic and American Indian women that reside in rural areas of Arizona, whether throughout the State or along the U.S.-Mexico border, are two underserved populations in Arizona with low rates of breast and cervical cancer screening that need to be addressed in order to reduce the burden of cancer in these populations.

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20

Capua, Christopher James. "Comparative Cytotoxicity of an FDA-approved Cancer Drug to Extracts of Atriplex confertifolia on Human Breast and Cervical Cancer Cells." BYU ScholarsArchive, 2008. https://scholarsarchive.byu.edu/etd/1703.

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The severity and number of people affected by cancer is a worldwide problem with millions of people affected annually. The search for treatment and cures of cancer continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, most from plants located in tropical regions. However, this study reports that extracts of Atriplex confertifolia, a native North American plant, has significant bioactivity against human breast cancer cell lines MCF-7, 435, and 231, and HeLa cells (cervical cancer cells). The bioactivity of A. confertifolia extracts of these cells lines was compared to an FDA-approved cancer drug and an industry-standard leukocyte control cell line. Active portions of the extracts were found primarily in the polar fractions of the plant. A dose-response curve of the extracts clearly showed significant cell death similar to the FDA-approved drug. The plant extracts did not inhibit the viability of the leukocyte cell line. Cancer cell death was followed as a function of time and concentration. Cell death appears to be a result of apoptosis.

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21

Loh, Yet Hua. "Diet, MGMT and SMAD7 gene variants and breast, prostate and colorectal cancer risk : results from the EPIC-Norfolk study." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608981.

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22

Hicks, Blánaid. "Modifiable risk factors and cancer survival : an investigation of pharmacological exposures, smoking and survival among breast and colorectal cancer patients." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695367.

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The aim of this thesis was to examine modifiable risk factors that may influence cancer survival in colorectal and breast cancer patients, focusing on investigations of pharmacological exposures as well as smoking. While there is extensive evidence of the effects of smoking on cancer incidence, less is known of the effects of continued smoking after a cancer diagnosis on survival. A systematic review and meta-analysis conducted as part of this thesis, identified 20 studies that assessed the impact of smoking on colorectal cancer survival. Overall, this study found that smoking after a colorectal cancer diagnosis reduced colorectal cancer-specific mortality and disease-free survival, as well as overall survival. With a growing number of cancer survivors, many of whom are older and are regular users of common medications for co-morbidities, the exploration of possible effects of these medications on cancer outcomes is of particular importance. A growing body of evidence, both pre-clinical and epidemiological, suggests a role for many medications commonly prescribed in the general practice setting in cancer progression. Utilising linked data sources from United Kingdom cancer registries and the Clinical Practice Research Datalink, a number of medications were investigated in colorectal and/or breast cancer patients, including beta-blockers, ACEls/ARBs, statins, bisphosphonates and clopidogrel. The findings from this thesis suggest that there should be increased efforts in the clinical setting to support smoking cessation among CRC patients. While pharmacological studies largely revealed null results, reassuringly they suggest both ARB's and clopidogrel are safe for use in cancer patients. The protective associations on cancer mortality observed with statin use require confirmation in large, observational studies before randomised controlled trials of statin use in the adjuvant setting can be recommended. As all the drugs investigated in this thesis are generally well tolerated and the frequency with which they are prescribed, further research in this area is warranted.

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23

Ralaidovy, Ambinintsoa Haritiana. "Efficiency in health ressource allocation : three empirical studies in Eastern Sub-Sahara Africa and Southeast Asia." Thesis, Université Clermont Auvergne‎ (2017-2020), 2019. http://www.theses.fr/2019CLFAD016.

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La définition des priorités en matière de santé, dans le contexte de la couverture sanitaire universelle, met l'accent sur trois valeurs : améliorer la santé de la population, garantir l'égalité d'accès aux services et la qualité de ceux-ci et éviter l'appauvrissement des usagers ou la sous-utilisation des services par ceux-ci en raison de dépenses non remboursables. L’efficience allocative peut être mesurée par rapport à l'une quelconque de ces valeurs, ou par rapport à l'ensemble, par différentes variantes de l'analyse coût-efficacité. Dans cette thèse, nous utilisons la « Generalized Cost-Effectiveness Analysis », une approche normalisée développée par le programme « Choosing Interventions that are Cost-Effective » de l’Organisation Mondiale de la Santé, (WHO-CHOICE), qui peut être appliquée à toutes les interventions dans différents contextes. En utilisant cette approche, notre travail de thèse fournit une estimation quantitative de l'efficience allocative des ressources pour trois groupes de problèmes de santé : les maladies transmissibles, les maladies non transmissibles, les accidents de la circulation, en mettant l'accent sur deux régions économiquement et épidémiologiquement différentes : l'Afrique subsaharienne de l’Est et l'Asie du Sud-Est. Nos objectifs étant d’éclairer les débats sur les politiques de santé, d’améliorer le corpus mondial de connaissances sur le rapport coût-efficacité de différentes interventions en fournissant davantage d’informations sur l’efficience de l’allocation de ressources pour les trois groupes de problèmes de santé précités et de contribuer aux discussions sur l’élaboration des programmes de soins de santé universels
Priority setting in health, in the context of Universal Health Coverage, emphasizes three values: improving population health, ensuring equity in access to and quality of services and avoiding impoverishment or underutilization of services as a result of out-of-pocket expenditures. Allocative efficiency can be measured with respect to any one of these values, or with respect to all together by different variants of Cost-Effectiveness Analysis. In this thesis, we use the Generalized Cost-Effectiveness Analysis, a standardized approach developed by the World Health Organization’s programme, ‘Choosing Interventions that are Cost-Effective’ (WHO-CHOICE) that can be applied to all interventions in different settings. This thesis provides a quantitative assessment of allocative efficiency within three health categories: communicable diseases, noncommunicable diseases, and road traffic injuries, focusing on two economically and epidemiologically diverse regions: Eastern sub-Saharan Africa and Southeast Asia. Our objectives are to inform health policy debates, improve the world’s body of knowledge on the cost-effectiveness of different interventions by providing more information on the allocative efficiency in those three disease groups and contribute to discussions on Universal Health Care packages

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24

Reynolds, Victoria Anne. "Cancer and Psychological Distress: Examining the Role of Neighborhood Social Cohesion." Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1510833570995311.

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25

Magnusson, Kristina. "Protein Expression Profiling of Cancer Biomarkers." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265513.

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The Human Protein Atlas project is a Swedish research initiative that uses antibody-based proteomics for large scale protein profiling in human tissues and cells. Affinity-purified antibodies are produced within the project and used for immunohistochemical staining on tissue micro arrays (TMAs) in order to map the human proteome and publish the result in a protein atlas (www.proteinatlas.org). In this thesis, TMAs were used for analysis of protein expression patterns in order to identify and explore potential biomarkers of clinical relevance. In Paper I, protein expression of SATB2 was studied in colorectal cancer. The results show that SATB2 is a sensitive and specific biomarker for colorectal cancer, staining 85% of all investigated tumors. Moreover, SATB2 in combination with CK20 showed positivity in 97% of all colorectal carcinomas and is therefore suitable as a complementary tool in clinical differential diagnostics of cancer. In Paper II, ANLN was explored as a prognostic biomarker for breast cancer. A high nuclear fraction of ANLN in breast cancer was significantly correlated to large tumor size, high histological grade, hormone receptor negative tumors, high proliferation rate and poor prognosis. Furthermore, ANLN depletion in breast cancer cell lines resulted in cell cycle arrest and cellular senescence with altered cell morphology. In Paper III, young age at breast cancer diagnosis was investigated as an independent risk factor for poor prognosis. TMAs were produced from a selection of patients from a previously defined register-based cohort. The analysis shows that young women with luminal B tumors have a 2.2-fold higher risk of dying of breast cancer compared to older women. In Paper IV, vascular expression of CD93 was explored by image analysis of the tissue-based breast cancer cohort produced in Paper III. The analysis shows that young women with breast cancer display a significantly higher CD93-positive vessel area in their tumors. High CD93-positive vessel area was significantly associated with hormone receptor negative tumors, grade, Ki-67, EGFR and a poor prognosis. In conclusion, this thesis shows that protein expression profiling using TMAs is an important tool for identifying and exploring potential novel biomarkers for cancer.

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26

Kadi, Mai. "Reproductive factors and breast cancer and colorectal cancer incidence and mortality among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition (EPIC)." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/49223.

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Cancers of the breast and colorectum are two of the most frequently diagnosed malignancies worldwide and despite improvements in treatment and survival, are leading causes of death. Reproductive factors, such as age at menarche, childbirth and age at menopause have been consistently linked to risk of developing breast cancer while exposure to exogenous hormones through use of oral contraceptives (OC) and hormone therapy (HT), are associated with increased risk of breast cancer but a reduced risk of colorectal cancer. These observations support the hypothesis that variation in endogenous hormone pathways contribute to breast and colorectal cancer development. However, while a substantial body of literature has established the significance of reproductive factors and exogenous hormone use in the initiation of these tumours, data on their association with mortality among breast and colorectal cancer patients are limited. To further knowledge on the role of reproductive factors and exogenous hormone use on the natural history of breast and colorectal cancer, a comprehensive assessment of these factors in relation to breast and colorectal cancer development as well as survival was undertaken among participants of the European Prospective Investigation into Cancer (EPIC). Specifically, among 150,251 women defined as postmenopausal at study baseline, the association of age at first and last menstruation, history of pregnancy, number of full-term pregnancies, the age at birth of the first and last child, breast feeding, accumulative breast feeding duration, and ever use of oral contraceptives and hormone therapy was investigated in relation to (i) breast cancer incidence, (ii) all-cause and breast cancer-specific mortality amongst breast cancer patients, (iii) colorectal cancer incidence and (iv) all-cause and colorectal cancer-specific mortality among colorectal cancer patients. Statistical analyses were conducted using Cox proportional hazards modelling with adjustment for established breast and colorectal cancer risk factors. In multivariable analyses, a later age at menarche was associated with associated with 11% reduced risk of breast cancer ( hazard ratio [HR] ≥15 vs 12 years = 0.89, 95% confidence intervals [CI]= 0.80-1.00; P-trend=0.0001); older age at menopause was found to be associated with increased risk of breast cancer (>55 vs ≤50 HR=1.27, 95% CI=1.10-1.47; P-trend < 0.0001); further giving birth to at least one child significantly reduced the risk of developing breast cancer by 16% (HR=0.84, 95% CI= 0.77-0.91) and reduced the risk of all-cause and breast cancer-specific death among breast cancer patients by 37% (HR=0•63, 95%CI: 0.46-0.86) and 45% (HR= 0.55, 95% CI= 0.37-0.82) respectively, compared to nulliparous women. Women with >4 children were at 26% reduced risk of breast cancer expressing oestrogen receptors (ER) compared to women who had one child (HR=0.74, 95%CI: 0.64-0.86; P-trend=0.002). Breast cancer patients who expressed the ER and had at least one pregnancy were at 57% reduced risk of death compared to nulliparous patients who expressed ER (HR= 0.43, 95%CI: 0.26-0.71). The use of exogenous hormones in the form of oral contraceptives and postmenopausal hormones was found to reduce the risk of developing colorectal cancer in postmenopausal women by 15% (OC users vs non-users HR= 0.85, 95%CI: 0.76-0.95) and 14% (HT users vs non-users HR= 0.86, 95% CI= 0.0.79-0.96). However, it seems that hormone therapy users have 28% higher risk of fatal colorectal cancer compared to non-users (HR=1.28, 95%CI: 1.01-1.61). The results of this large-scale prospective investigation indicate that reproductive factors and use of exogenous hormones influence the development of breast and colorectal cancer and may also be associated with survival among patients with these malignancies. If confirmed in other studies, these findings may be further explored in prognostic modelling and may help inform treatment and surveillance of high-risk groups.

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Pendrick, Danielle M. "An Evaluation of the Client Navigator Program for Enhanced Breast and Cervical Cancer Screening Among Underserved Women in the State of Georgia." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/iph_theses/181.

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Screening for breast and cervical cancers can reduce morbidity and mortality through early detection, yet many women are not getting regular lifesaving screenings as recommended. 2 The National Breast and Cervical Detection Program (NBCCEDP) was established in 1990 in order to provide low-income, uninsured, and underserved women access to breast and cervical cancer screening and diagnostic services. Georgia’s participation in the NBCCEDP led to the development of The Breast and Cervical Cancer Program (BCCP), which provides cancer screening to women 40 to 64 years of age who are uninsured and/or underinsured and at or below 200% poverty level. Deaths from breast and cervical cancers could be avoided if screening rates increased among women at risk. In order to better eliminate barriers to screening, Georgia’s Breast and Cervical Cancer Program uses client navigators to communicate with minority populations. The purpose of my thesis study was to assess the effectiveness of the Client Navigator Program utilized to enhance breast and cervical cancer screening rates for women throughout Georgia. Evaluation findings demonstrated that personal characteristics of Client Navigators, internal characteristics of the program itself, resources provided by the program, and program partnerships were the areas of greatest program strength. Funding was repeatedly listed as the greatest program threat. Findings from this study provide insights for how the overall program can be improved in the future, and thus, improving health outcomes for women who are at greatest risk of breast and cervical cancer throughout the state.

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Habib, Sanzida Zohra. "South Asian immigrant women’s access to and experiences with breast and cervical cancer screening services in Canada." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42855.

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A qualitative feminist study, informed by social constructionist epistemology, antiracist theories and intersectionality perspectives, was conducted in order to understand South Asian immigrant women’s access to and experiences with breast and cervical cancer screening services in Canada. Particular attention was paid to the wider context of their lives and their experiences of migration, resettlement, integration and general access to the Canadian healthcare system. The study also explored how the broader systems, structures and policies in Canadian society shape South Asian immigrant women’s participation in and access to cancer screening services. Thirty one South Asian immigrant women were interviewed in individual, couple and group settings in greater Vancouver. Research findings indicated that women’s age, length of stay since immigration, educational and generational status, not/having a family history or symptoms impact their use or lack of use of cancer screening services; but these factors also intersect in complex ways with various systemic and structural issues including not having a recommendation from physicians, women’s financial instability, access to income, employment, settlement services and community resources, levels of socioeconomic integration and familiarity with the Canadian healthcare system, and gender roles and responsibilities. Women’s narratives also showed that the immigration factor amplify the intersecting forms of inequities and the social determinants of health such as gender, class, poverty, racialization and discrimination, and affect women’s physical and mental health and access to healthcare services, cancer screening being one of them. An intersectional analysis revealed that the gendered and racialized immigration and integration policies, multicultural discourses and neoliberal ideologies and practices intersect to situate South Asian immigrant women into racialized and disadvantaged situations as the ‘other’ wherein access to preventive cancer screening services becomes especially challenging. South Asian women’s access to cancer screening and other healthcare services needs to be understood beyond the attempts to know their cultural health beliefs and practices, and beyond the neoliberal ideas of ‘self-care,’ ‘individual responsibility,’ ‘patient empowerment,’ and ‘culturally sensitive care.’ Also, equitable access to health care cannot be ensured without resisting these women’s racialized position as the ‘other’ and addressing the social, political, historical, material and structural inequities in Canadian society.

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Nguyen, Anh. "Suc Khoe La Quan Trong Hon Sac Dep! Health is Better than Beauty! Improving Breast and Cervical Cancer Screening Outcomes among Vietnamese Women." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/186.

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Vietnamese women experience cancer screening disparities and inconsistent adherence to screening guidelines. The goal of this study was to implement and evaluate a breast and cervical cancer screening intervention to promote cancer screening knowledge, attitudes, self-efficacy, intention, and behavior for Vietnamese women. Secondary objectives of the study included examining the relationships between cultural variables (e.g., acculturation, ethnic identity, religiosity, and collectivism) and cancer screening variables. The study enrolled 102 women from the greater Richmond metropolitan area. Participants were assigned to an intervention group or a print material control group. In the intervention session, participants were exposed to information on female cancers and were taught how and where to access Pap tests and clinical breast exams (CBE). Follow-up data were collected six months after the intervention to determine whether or not there were longer-term program effects. Intervention participants also took part in focus groups that examined their reactions, thoughts, feelings, and experiences in regards to the intervention. In addition, focus groups explored participants’ sources of motivation for cancer screening and whether they shared information obtained in the sessions with other individuals. The intervention was effective in promoting immediate and longer-term gains in breast and cervical cancer knowledge, attitudes towards screening, self-efficacy for screening, and actual screening behaviors. The study’s findings indicated that acculturation was linked to higher levels of self-efficacy and screening behavior and less positive attitudes towards screening. Personal and social extrinsic religiosity were associated with more positive attitudes towards screening. Social extrinsic religiosity was also associated with more self-efficacy for screening and screening behavior. Intrinsic religiosity was linked to lower levels of self-efficacy for screening. Focus group discussions revealed that the women shared cancer-related information with friends, female family members, and husbands. Focus group discussions also revealed that emphasis on caretaking roles may help increase women’s adherence to screening guidelines. This study provides evidence for the effectiveness of culturally-tailored strategies in developing cancer screening interventions for the Vietnamese population. This study also demonstrates how health information is transmitted across informal channels within faith-based communities.

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Starczewska, J. M. "Predictors of breast and cervical cancer screening uptake prior to the introduction of centralised nationwide screening in Poland." Thesis, University of Salford, 2013. http://usir.salford.ac.uk/30863/.

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Background: Introduction of nationwide breast and cervical screening programmes in Poland (2006) created an unprecedented opportunity to explore the predictors of breast and cervical cancer prophylactic behaviours in a society unexposed to population screening. The study aims to add to the body of knowledge on predictors that could be common for other countries in a similar geo-political situation, aiming to introduce nationwide breast and cervical screening programmes. Methods: A data subset (N=4,290) from a large representative survey (N=7,948) on cancer knowledge and prophylaxis, conducted by the Cancer Oncology Institute in Warsaw close to the introduction of nationwide breast and cervical cancer screening, was used in this thesis. Behaviours and knowledge were described and logistic regression used to identify predictors of mammography and cytology uptake. Results: Women’s level of cancer knowledge was evenly distributed (49.2% low and 50.8% high scores). However, knowledge on cervical cancer was lower than for breast. Higher knowledge was linked to higher education, better material conditions, cancer diagnosis, or practicing any type of the studied prophylaxis and lower levels of knowledge was associated with being aged 18-24 or ≥70 y.o., being widowed, and living in village. Even though 93% (N=3,970) of respondents were aware of the need for breast self-examination (BSE), only 32.3% regularly practiced BSE. Majority (92.3%, N=3,943) knew that mammography can allow early cancer detection but only 52.5% ≥ 50 y.o. (32.1% all ages) declared ever having it. Similarly, 90.7% (N=3,871) knew that cytology allows early detection of cancer and 78.8% have ever undertaken it cytology but only 53.6% had it done every 1-3 years. Up to 4% indicated test unavailability of either test as the reason for non-attendance. The most common barriers included: feeling of no need for such test (37.9-44.9%) and lack of referral (28.7%-39.2%). Women with the highest education levels, the 3 ones living in cities above 100,000 inhabitants, or with highest cancer knowledge were the most likely to ever get screened for breast and cervical cancers. Additionally BSE was found to predict mammography whilst cytology was also predicted by: household size, marital status, having a family member or a friend with cancer. Conclusions: Low screening uptake could be reflective of the fact that there was no nationally available screening but only a small proportion reported non-attendance due to unavailability of tests. This suggests that the uptake was driven by other factors (e.g., cancer knowledge, education) than population screening availability. Particular attention should be paid to the provision of cancer related knowledge. A follow up study is recommended to assess whether women’s knowledge and screening behaviours improved since the conduct of this survey.

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Barker, Laura C. "The dynamics of the serum concentration of CEA, CA15-3 and CA19-9 and survival in patients treated for advanced breast and colorectal cancer. The determination of the prognostic correlates of changes in tumour markers CEA, CA15-3 and CA19-9 during chemotherapy treatment for advanced breast and colorectal cancer." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/4443.

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There is evidence that kinetics of tumour markers (TMs) CEA, CA15-3 and CA19-9 provide valuable information about disease state over time in patients with advanced breast and colorectal cancer but the literature contains differences in methodology so comparing findings is difficult. By modifying criteria developed by Rustin and colleagues [1-5] in ovarian carcinoma we have retrospectively identified a subset of patients (those with progressive (P) TMs) where survival is significantly reduced compared with those with responsive (R) TMs. This is true for CEA, CA15-3 and CA19-9 at the first chemotherapy given in advanced disease (chem1) (Hazard ratios (HR) = 9.99, 8.89, 5.75, P ¿ 0.001 in all cases) and CEA and CA19-9 at the second chemotherapy (chem2) (HR = 7.95, 9.00, P = 0.001 and 0.002 respectively) in patients with breast cancer. It is also true for CEA at chem1 in patients with colorectal cancer (HR = 2.51, P <0.001). Further studies are necessary to see if treatment directed by these criteria can influence survival. CEA and CA19-9 Rustin category in colorectal patients and CA15-3 Rustin category in breast patients correlated significantly with radiological category at chem1 and chem2 (CEA rs = 0.45 and 0.43, CA19-9 rs = 0.26 and 0.35, CA15-3 rs = 0.28 and 0.44). CA19-9 also correlates with radiological category at chem2 (rs = 0.38) in breast patients. This provides valuable information because RECIST criteria can delay radiological identification of disease progression compared with WHO criteria [6, 7] and new therapies may act to stabilise tumour growth rather than reduce it [8].
Oncology Research Trust Fund at Airedale NHS Trust

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Doat, Solène. "Rôle de la consommation d'Anti-inflammatoires Non Stéroïdiens (AINS) dans la survenue du cancer de la prostate, du sein, et colorectal en France." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS550/document.

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Contexte – Les cancers de la prostate, du sein, et colorectaux sont parmi les cancers les plus fréquents dans les pays développés, et, même si plusieurs facteurs de risque sont aujourd’hui bien établis pour ces cancers, leur étiologie reste encore largement à expliquer. L’inflammation chronique est fortement suspectée de jouer un rôle dans la survenue de ces cancers et la présence, dans les tissus tumoraux, d’infiltrats inflammatoires localisés pouvant être considérés comme des lésions précancéreuses, contribue à renforcer l’hypothèse d’un lien possible entre inflammation chronique et cancers. Dans ce contexte, de nombreuses études épidémiologiques se sont intéressées au rôle des Anti-Inflammatoires Non Stéroïdiens (AINS) dans les cancers. En effet, les médicaments ayant des propriétés anti-inflammatoires comme les AINS, dont l’aspirine, et les anti-inflammatoires inhibiteurs sélectifs de la cyclo-oxygénase 2 (COX-2), pourraient diminuer le risque de survenue de ces cancers.Objectifs – L’objectif général de cette thèse a été d’étudier le rôle de la consommation d’AINS, dont l’aspirine, les AINS usuels et les inhibiteurs sélectifs de la COX-2 dans la survenue des cancers de la prostate, du sein et colorectaux.Population et méthodes – Ce travail s’est appuyé sur les données de l’Echantillon Généraliste des Bénéficiaires (EGB) de l’Assurance Maladie pour les trois cancers d’intérêt et sur les données d’une étude cas-témoins réalisée en population générale dans le département de l’Hérault (EPICAP) pour le cancer de la prostate. Pour les données de l’EGB, une cohorte fixe de 426 410 personnes présentes au 1er janvier 2007 a permis d’identifier les cas incidents entre 2008 et 2012 à partir de différents algorithmes. L’exposition aux AINS a été identifiée à partir du 1er janvier 2005 jusqu’à la date de fin d’observation : date de survenue du cancer, date de décès ou date de censure fixée au 31 décembre 2012. Un temps de latence d’au moins un an a été défini entre l’exposition aux AINS et la survenue du cancer d’intérêt. Pour les données d’EPICAP, 819 cas incidents de cancer de la prostate et 879 témoins de population générale, de même âge en moyenne que les cas, ont été interrogés en face-à-face, à l’aide d’un questionnaire standardisé, notamment sur leur consommation d’AINS.Résultats – A partir de la cohorte issue de l’EGB, des résultats préliminaires montraient une augmentation du risque de cancer de la prostate (RR=1,30 [1,17-1,46]) et du sein (RR=1,29 [1,14-1,46]) chez les patients exposés aux AINS et une absence d’association pour les cancers colorectaux (RR=0,92 [0,82-1,05]). En revanche, une association négative était observée pour les cancers de la prostate (RR=0,85 [0,74-0,96]) et colorectaux (RR=0,77 [0,66-0,90]) lorsque le temps de latence considéré était de six ans. L’étude EPICAP a montré que la consommation d’AINS était associée négativement au cancer de la prostate (OR=0,77 [0,61-0,98]). Cette association était plus prononcée pour une fréquence de consommation quotidienne (OR=0,75 [0,33-0,92]) ou d’une consommation pluriquotidienne (OR=0,38 [0,18-0,79]), et pour une durée entre 5 à 10 ans (OR=0,55 [0,33-0,92]). L’association était renforcée pour une molécule ayant une activité anti-COX-2 préférentielle (OR=0,48 [0,28-0,79]). Enfin, une association négative était également observée pour les cancers de la prostate de haut grade (Gleason score =7 (4+3) ou GS>7) avec un OR de 0,62 [0,41-0,95].Conclusion – L’ensemble de ce travail de thèse a montré que la consommation d’AINS semblait être associée négativement à la survenue du cancer de la prostate et aux cancers colorectaux. Pour le cancer de la prostate cette thèse s’est appuyée sur deux bases de données et deux méthodologies différentes, permettant d’appréhender les limites et les forces de chacune
Background – Prostate, breast, and colorectal cancers are among the most common cancers in developed countries. Many risk factors have been identified over the years but could explain only a part of the new cases. Chronic inflammation is highly suspected to play a role in the carcinogenesis of those cancers and the presence of inflammatory infiltrate in tumoral tissue, considered as precancerous lesions, reinforced this hypothesis. In this context, several epidemiological studies have investigated the potential role of Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer occurrence. Indeed, NSAIDs such as aspirin and non-aspirin NSAIDS including selective inhibitors of cyclo-oxygenase 2 (COX-2) may decrease the incidence of those cancers.Objectives – The main objective of the thesis was to investigate the role of NSAIDs use including aspirin, non-aspirin NSAIDs and selective inhibitors of COX-2 in the occurrence of prostate, breast and colorectal cancers.Population and methods – This work was based on the General Sample of health insurance Beneficiaries (EGB) for the three localizations of cancer and on the data of a population-based case-control study carried out in the département of Herault (EPICAP) for prostate cancer. In the EGB study, a cohort of 426 410 persons present in the database in January 1st, 2007 allowed to identify incident cases between 2008 and 2012 based on different algorithms. Exposure to NSAIDs was determined from January 1st, 2005 until the end of the follow up defined as either cancer incident date, date of death, or censure date fixed as December 31st, 2012. A latency of at least one year between the beginning of exposure to NSAIDs and the cancer occurrence was taken into account. For the EPICAP study, 819 incident prostate cancer cases and 879 population-based controls, frequently matched by age to the cases, were face-to-face interviewed using a standardized questionnaire, specifically on their NSAIDs use.Results – From the EGB cohort, preliminary results showed a positive association between all NSAIDs use and prostate or breast cancer occurrence (RR=1,30 [1,17-1,46], RR=1,29 [1,14-1,46], respectively), while no association was found with colorectal cancer occurrence (RR=0,92 [0,82-1,05]). These associations became negative associations when a latency of six years was taken into account in prostate and colorectal cancer (RR=0,85[0,74-0,96], RR=0,77 [0,66-0,90], respectively). In the EPICAP study, NSAIDs use was negatively associated with prostate cancer (OR=0,77 [0,61-0,98]). This association was more pronounced with daily intake (OR=0,75 [0,33-0,92]) or more than once a day (OR=0,38 [0,18-0,79]), and for a duration of five to ten years (OR=0,55 [0,33-0,92]). The negative association was reinforced for preferential anti-COX-2 NSAIDs (OR=0,48 [0,28-0,79]), and for patient with high grade prostate cancer (Gleason score, GS=7 (4+3) or GS>7 : OR=0,62 [0,41-0,95]).Conclusion – This work showed that NSAIDs use was negatively to prostate and colorectal cancer occurrence. For prostate cancer, this thesis was based on two different databases (a medical and administrative database and a case-control study) and used two different methodologies, allowing comparison about strengths and limits of both

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Lambert, Sylvie. "[An] in depth exploration of health information-seeking behavior among individuals diagnosed with prostate, breast, or colorectal cancer." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=92690.

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Seeking cancer information is key in coping with the feelings (e.g., fear, uncertainty) and other challenges (e.g., treatment decision-making) confronting individuals diagnosed with cancer. Despite recognition of a variation in why, when, how, and where individuals diagnosed with cancer seek information, few efforts have been made to systematically document patterns in information-seeking. Aim: To explore individuals' patterns of health information-seeking behaviors (HIS B) including the type, amount, and sources ofinforn1ation and the strategies used to process and/or manage cancer information.
La recherche d'information sur Ie cancer est d'une importance determinante pour les personnes atteintes de cette maladie dans Ie contexte OU elles ont gerer des emotions intenses (p. ex. : peur, incertitude) et font face plusieurs defis (p. ex. : processus de decision relatif au traitement). Des variations concernant la recherche d'information par les individus diagnostiques avec un cancer ont ete observees et reconnues notamment en termes des raisons qui motivent la recherche d'information et des moyens utilises pour obtenir l'infomlation desiree. Cependant, a ce jour, peu d'efforts ont ete deployes pour documenter de maniere systematique les differents types de comportements de recherche d'information.

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Pereira, Abrantes Manuela. "Hétérogénéité des neutrophiles et leurs écosystèmes dans l’immunosurveillance au cours de la tumorigenèse." Electronic Thesis or Diss., Lyon 1, 2023. http://www.theses.fr/2023LYO10147.

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Le neutrophile est la cellule immunitaire la plus représentée dans le sang chez l’Homme, dont la migration au site inflammatoire est rapide. Le rôle du neutrophile a largement été décrit dans des contextes infectieux, auto-immunitaires et allergiques mais reste controversé dans le cancer, notamment dans les mécanismes d’immunosurveillance précoce. Le neutrophile se révèle être une population hétérogène tant phénotypiquement que fonctionnellement. L’origine et la compréhension de l’hétérogénéité des neutrophiles est un sujet émergent et croissant, mais aucune étude à ce jour ne décrit l’évolution de l’hétérogénéité des neutrophiles à différents stades. L’objectif de ma thèse est de caractériser cette hétérogénéité au sein des tissus au cours de la tumorigenèse, à partir de deux modèles d’études. Mon premier projet s’est intéressé au cancer colorectal (CCR) chez l’Homme de par l’accès privilégié à des échantillons de tissus adjacents colorectaux (AT), de tissus prénéoplasiques (polypes, P) et d'adénocarcinomes (ADK), frais, synchrones et pairés à partir de patients subissant des colectomies partielles ou totales. Des quantifications protéomiques démontrent que les neutrophiles représentent la principale augmentation de cellules immunitaires innées au sein de l'ADK. Pour la première fois, les profils transcriptomiques de neutrophiles triés et de leurs partenaires cellulaires par RNA-seq et single cell RNA-seq (scRNA-seq) au cours de la tumorigenèse ont été établis et intégrées pour déchiffrer l'hétérogénéité, l’évolution et les interactions cellulaires clés des neutrophiles, au cours du CCR. Alors que le microenvironnement du P et de l’ADK sont similaires et distinct de l’AT, le transcriptome des neutrophiles de P et d’AT sont corrélés mais différents de ceux de l’ADK. Ces résultats suggèrent une niche pré-inflammatoire dans le P favorable aux modifications des neutrophiles, précédant l'inflammation cancéreuse, favorisant la migration et l’activation des cellules myéloïdes. Les neutrophiles du P présentent des propriétés fonctionnelles (e.g. dégranulation, activation, production de cytokines) tandis que les neutrophiles de l'ADK présentent un état “d’épuisement” associé à un profil plutôt pro-tumoral (i.e. perte de fonctions canoniques et profil pro-tumoral). Le scRNA-seq de neutrophiles triés identifie 8 clusters distincts, dont deux sont spécifiquement enrichis dans l’AT et l’ADK. Le cluster enrichi dans l’AT est associé à des signatures anti-tumorales tandis que le cluster associé à l'ADK démontre des caractéristiques pro-tumorales, basées sur des analyses d’enrichissement de signatures issues de données publiques. Les analyses de trajectoire démontrent un continuum de l’AT, à P et ADK avec 3 trajectoires distinctes, où un cluster unique de neutrophiles exprimant des gènes induits par les interférons et enrichi dans l’ADK se distingue des autres. Le second projet s’est basé sur un modèle murin de carcinogenèse mammaire spontanée MMTV-NeuT pour lequel, à la différence du modèle chez l’Homme, nous avons accès aux différents stades tumoraux mais également au sang et aux organes lymphoïdes primaire (moelle osseuse) et secondaire (rate). Les analyses transcriptomiques de neutrophiles triés révèlent des états phénotypiques et fonctionnels distincts selon l’organe et le stade tumoral analysé. De manière originale, nous avons mis en évidence l’existence de neutrophiles EpCAM+ uniques aux tissus tumoraux et constituant 60 à 90% des neutrophiles totaux au cours de la tumorigenèse. L’expression d’EpCAM n’est pas endogène mais semblerait provenir de fragments membranaires exogènes à la surface du neutrophile, suggérant un mécanisme de trogocytose voire de trogoptose des cellules prénéoplasiques et tumorales. De futures études fonctionnelles permettront d’élucider le mécanisme et le rôle des neutrophiles EpCAM+
The neutrophil is the most abundant immune cell in the human blood that migrates rapidly to the inflammatory site. The role of neutrophils has been extensively described in infectious, autoimmune, and allergic contexts, but it remains controversial in cancer, particularly in early immune surveillance mechanisms. Neutrophils are a heterogeneous population, both phenotypically and functionally. The origin and understanding of neutrophil heterogeneity are emerging and increasingly studied, albeit to date, no study has described the evolution of neutrophil heterogeneity at different stages. The aim of my thesis is to characterize this heterogeneity within tissues during tumorigenesis, using two models. My first project focused on colorectal cancer (CRC) in humans, taking advantage of a privileged access to fresh, synchronous, and paired adjacent colorectal tissue samples (AT), preneoplastic tissues (polyps, P), and adenocarcinomas (ADK), from patients undergoing partial or total colectomies. Proteomic quantification demonstrated that neutrophils represent the main increase in the innate immune compartment within ADK. For the first time, transcriptomic profiles of FACS-sorted neutrophils and their cellular partners using RNA-seq and single-cell RNA-seq (scRNA-seq) throughout tumorigenesis were established and integrated to decipher the heterogeneity, evolution, and key cellular interactions of neutrophils in CRC. While the microenvironment of P and ADK were similar and distinct from AT, the transcriptome of P and AT neutrophils were correlated but different from ADK-associated neutrophils. These results suggest a pre-inflammatory niche in P that favors neutrophil modifications, preceding cancer-related inflammation, promoting migration and activation of myeloid cells. P-associated neutrophils exhibited functional properties (e.g. degranulation, activation, cytokine production), while ADK-associated neutrophils showed an "exhausted" state associated with a more pro-tumoral profile (i.e. loss of canonical functions and pro-tumoral profile). scRNA-seq of FACS-sorted neutrophils identified 8 distinct clusters, two of which were specifically enriched in AT and ADK. The AT-enriched cluster was associated with anti-tumoral signatures, while the ADK-enriched cluster demonstrated pro-tumoral characteristics, based on enrichment analyses of publicly available data signatures. Trajectory analyses showed a continuum from AT to P and ADK with three distinct trajectories, where a unique ADK-enriched cluster of neutrophils expressing interferon-stimulated genes stood out from the others. The second project was based on a mouse model of spontaneous mammary carcinogenesis, MMTV-NeuT, for which, unlike the human model, we have access to breast tissues at different stages as well as blood and primary (bone marrow) and secondary (spleen) lymphoid organs. Transcriptomic analysis of FACS-sorted neutrophils revealed distinct phenotypic and functional states depending on the organ and tumor stage. Interestingly, we unveiled the existence of a unique EpCAM+ neutrophil population in tumor tissues, representing 60 to 90% of total neutrophils throughout tumorigenesis. EpCAM expression was not endogenous but seemed to originate from exogenous membrane fragments on the surface of neutrophils, suggesting a mechanism of trogocytosis or even trogoptosis of preneoplastic and tumor cells. Further functional studies will elucidate the mechanism and the role of EpCAM+ neutrophils

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Somayaji, Kamila. "Breast and Cervical Cancer Screening in Virginia: The Impact of Insurance Coverage and the Every Woman's Life Screening Program." VCU Scholars Compass, 2007. http://hdl.handle.net/10156/1890.

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Muzenda, Trish. "Comparing women's unprompted and prompted knowledge of breast and cervical cancer risk factors and symptoms in Sub- Saharan Africa." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31031.

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Breast and cervical cancer are leading causes of female cancer morbidity and mortality in Sub-Saharan Africa (SSA). Despite the high burden of disease, women’s knowledge of evidence-based risk factors and symptoms remains low. To adequately address the apparent knowledge deficits, the underlying knowledge in communities needs to be measured, so as to identify important gaps and contextually address them. To date, cancer knowledge in SSA has been measured using either prompted or unprompted question formats, yielding varying knowledge scores. However, there has been little exploration on the impact of using either question format for assessing disease awareness. This study sought to measure the differences in breast and cervical cancer risk factors and symptoms knowledge reported through prompted and unprompted questions, in South Africa (SA) and Uganda (UG). This was a descriptive cross-sectional study drawing on data collected during validation of an interviewer administered questionnaire (African Woman’s Awareness of Cancer - AWACAN) measuring breast and cervical cancer awareness in SSA. The sample included 139 women recruited from public sector primary health care facilities in two urban districts, Gulu (UG) and Cape Town (SA). Descriptive statistics were used to summarize participant’s socio-demographic characteristics and knowledge about breast and cervical cancer. Composite knowledge scores were calculated by adding up the number of correct responses per individual. The Wilcoxon Singed Rank test was used to compare differences between unprompted and prompted knowledge scores. Regression analyses were used to measure the relationship between unprompted and prompted knowledge. The median age of study participants was 42 years. The majority of women had not completed secondary education (57%) and were unemployed (64%). Unprompted knowledge was considerably lower than prompted knowledge for all breast and cervical cancer risk factors and symptoms. Median scores for unprompted knowledge of breast cancer risk factors (0) and symptoms (1) were significantly lower than for prompted at 6 and 14 respectively. Similarly, the median scores for unprompted knowledge of cervical cancer risk factors (0) and symptoms (1) were lower than prompted knowledge at 6 and 9 respectively. The difference between prompted and unprompted knowledge was least for classical breast and cervical cancer symptoms. For instance, the well-known breast cancer symptom ‘lump in the breast’ was recalled by 57% and 96% with unprompted and prompted questioning respectively. Unprompted questioning identified additional risk lay beliefs such as, ‘itching of the breast’. Combined use of unprompted and prompted questions provides more insight on breast and cervical cancer knowledge patterns in SSA. The low unprompted knowledge scores reported here demonstrate the need for health education interventions to improve knowledge of established breast and cervical cancer risk factors and whilst addressing any predominant lay beliefs about the disease in SSA. This dissertation is divided into three parts. Part A consists of the study protocol outlining the rational for undertaking this study as well as the proposed research methodology. Part B is the literature review that gives a summary of existing literature on the use of prompted and unprompted questions in measuring cancer knowledge thereby providing context for this study. Part C is a journal ready manuscript presenting the results and discussion of study findings.

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Lopresti, Alexia. "Etude des cellules tumorales circulantes en tant que biomarqueurs sanguins représentatifs des tumeurs solides." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0676.

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Les métastases sont responsables de 90% des décès par cancer. Les cellules tumorales circulantes (CTC) se détachent de la tumeur primaire pour migrer vers de nouveaux sites via la circulation sanguine. La rareté de ces cellules et l’absence de marqueurs robustes a limité leur caractérisation et leur utilisation en tant que biomarqueur tumoral. Au cours de ma thèse de doctorat, j’ai mis au point une nouvelle technique de détection des CTC simple, rapide et sensible par cytométrie en flux qui permet de tester la présence de CTC dans des échantillons de sang. Cette technique permet de discriminer les donneurs sains de ceux atteints de cancers et de suivre une réponse à un traitement, et peut s’adapter à différentes tumeurs. Ensuite, je me suis intéressée aux CTC, en les énumérant et caractérisant au niveau histologique, puis d’un point de vue fonctionnel, grâce à l’ajout de marqueurs spécifiques. A l’aide d’échantillons de sang de patientes atteintes de cancer du sein métastatique j’ai pu caractériser 4 populations de cellules circulant dans le sang, dont 2 associées à un moins bon pronostic. J’ai ensuite travaillé sur une cohorte de patients atteints de cancer du côlon (métastatique ou non), que j’ai suivi du diagnostic jusqu’à la rechute. J’ai ainsi constaté l’absence d’un marqueur d’agressivité, PTK7, sur les CTC, alors qu’il était exprimé sur les tumeurs primaires colorectales et les métastases associées. Ces résultats ont été confirmés in vivo. J’ai ainsi pu vérifier à l’aide d’un système de fluidique que PTK7 était perdu lors du passage des cellules en circulation et n’est donc pas un marqueur d’agressivité dans les CTC
Metastases are responsible for 90% of cancer related deaths. Circulating tumor cells (CTCs) detach from primary tumor before migrating toward new sites via blood vessels. Scarcity of these cells in circulation and the absence of robust marker allowing their isolation have limited their characterization and use as tumor biomarkers. During my PhD, I have set up a new technique for CTCs detection by flux cytometry that is easy, fast and sensitive. This technique allows, in less than an hour, to test the presence of CTCs in patient’s blood samples. This technique allows the discrimination of healthy donors from cancer patients and permits to follow a treatment response and is applicable to different tumors for CTC’s detection. Then, I have taken an interest in better characterizing CTCs, first by enumeration and histological characterization, then from a more functional point of view, using additional markers. To that end, I used blood draws from metastatic breast cancer patients; I characterized 4 populations of circulating epithelial cells in the blood, of whom two were associated to a bad prognostic. I have then worked on a cohort of colorectal cancer patients (metastatic or not), that I have followed from diagnostic until relapse. I noticed the absence of an aggressive biomarker, PTK7, on CTCs, even if it was expressed on corresponding primary colorectal tumors and metastases. I reported the same observations in vivo. I then exposed PTK7 expressing epithelial cells to a flux and saw that the micro-environment change could be responsible for the loss of PTK7 expression, and that this marker predicting aggressiveness on colorectal cancer is not a marker for CTCs

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Dempsey, Melanie C. "FACTORS THAT INFLUENCE BREAST CANCER DIAGNOSES IN VIRGINIA WOMEN 40-64 YEARS OLD WHO UTLIZED THE EVERY WOMAN’S LIFE PROGRAM 1998-2012." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4052.

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This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women. The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source of health information. Additionally, frequencies across all variables were explored and compared to state and national statistics, where appropriate. In this study, cancer and preventive health disparities reported in the literature persist within this sample of low income women. The binary regression analyses demonstrated that there are marginally worse outcomes for each level of decreasing income. Those with the most “wealth” were less likely to be diagnosed with invasive breast cancer and were more likely to obtain health information from a health provider. Additionally, it was determined that those without a prior mammogram were more likely to be diagnosed with breast cancer and the cancer was more likely to be invasive. The aims of the Every Woman’s Life program align with Affordable Care Act (2010) to strengthen health care and eliminate cancer disparities. Highlighting program characteristics and presenting these analyses allows policymakers, program officials and practitioners an opportunity to tailor health promotion activities while considering all tiers of influence.

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Meng, Huan. "Functional characterization of the DNA glycosylase, methyl-CpG binding domain protein 4 (MBD4)." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/11818.

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DNA methylation is a major form of epigenetic modification and involves the addition of a methyl group covalently to the 5-position of the cytosine pyrimidine ring, mostly within the context of CpG dinucleotides in vertebrate somatic cells. Methylation of CpG dinucleotides at promoter regions is generally associated with transcriptional repression. In this context, the methyl-CpG binding proteins (MeCPs) that are capable of recognition of methylated CpG dinucleotides are proposed to play a central role in DNA methylation associated transcriptional repression. Methyl-CpG binding domain protein 4 (MBD4) is an MeCP that possesses a glycosylase domain at its C-terminal, which can excise and repair both G:T and G:U mutations derived from DNA deamination at CpG dinucleotides, in addition to its Nterminal MBD binding domain. MBD4 has been associated with a number of pathways including DNA repair, apoptosis, transcriptional repression, and possibly DNA demethylation processes. However, the precise contribution of MBD4 to these processes remains unclear. To explore the functional repertoire of MBD4 I decided to undertake multiple protein interaction studies to identify potential partner proteins. I performed yeast 2-hybrid screens with an 11.5 day mouse embryonic cDNA library and multiple mass spectrometry of immunoprecipitates of tagged versions of MBD4 that were over-expressed in human cell lines. I detected ~380 potential interacting candidates with these assays. A significant number of candidates were detected in both assay systems. Chosen candidates were further validated by reciprocal co-IP of expressed partners and by immunofluorescence (IF) microscopy to determine their potential co-localisation in mouse and human cell lines. Subsequently, I identified the intervening domain of MBD4 as a novel protein interaction region for tested candidates. My analysis suggests that MBD4 can have a role in regulation of post-replication methyl-error repair/methylation machinery through its direct interaction with DNMT1 (previously shown), UHRF1 (novel) and USP7 (novel), as well as possible cross-talk to histone modification and chromatin remodelling pathways, through partners such as PRMT5 and ACF1. Interestingly the transcription regulatory components KAP1 and CFP1 not only interact with but also dramatically influence the stability of exogenously expressed MBD4 in human cells. In general positive validation by IP and IF demonstrates the robustness of the initial screens, and implies that MBD4 may impact upon several transcriptional and epigenetic networks along with a number of nuclear pathways that include transcriptional repression, DNA repair and RNA processing. To test for transcriptional aberration in the absence of Mbd4 function I profiled two independent mouse cell lines that lack MBD4 activity using Illumina MouseWG-6 v2.0 Expression BeadChip arrays. A number of genes were identified that are significantly up- or down- regulated in both Mbd4-/- MEFs. This included mis-expression of insulin-like growth factor-binding proteins and two paternally imprinted genes Dio3 and H19. The cohort of genes that were mis-expressed in the Mbd4-/- MEFs overlap with genes that responsed to tamoxifen exposure in an ER-positive ZR-75-1 xenograft model. In response to this observation I identified a potential interaction between MBD4 and estrogen receptor α (ERα) by co-IP and IF co-localisation. This suggests that MBD4 might potentiate transcription of estrogen regulated genes via a direct interaction with ERα, supporting a possible link between replication repair remodelling and steroid/thyroid hormone receptor transcriptional regulation. Additionally I performed a pathway analysis by which several developmental genes including Sox9, Klf2 and Klf4, were prioritised as possible MBD4 targets. On this basis I propose a role for MBD4 in acquired diseases such as cancers and autoimmune diseases via transcriptional regulation. I also performed a comparison of MBD4 DNA binding activity with MBD4 homologues from the Medaka fish (Oryzias latipes) and the amphibian, Xenopus laevis. I could show that DNA binding specificity to a series of methylated and mismatched probes is conserved regardless of the poor sequence conservation of the MBD domain of MBD4 between the species. I conclude that MBD4 is integrated in multiple pathways in the nucleus that includes DNA repair, chromatin remodelling, transcriptional regulation and genome stability.

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40

Mil, Rémy de. "Efficience de programmes de santé publique visant à réduire les inégalités de participation au dépistage organisé des cancers." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMC415/document.

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Contexte. L’augmentation de la participation au dépistage organisé des cancers et la réduction des inégalités sociales et géographiques de participation représentent un enjeu de santé publique majeur. Objectifs. Evaluer l’efficience de 2 interventions visant à augmenter la participation et à réduire les inégalités dans le dépistage organisé des cancers en France. Méthodes. Nous avons réalisé une analyse coût-efficacité du point de vue du financeur: 1) d’une invitation à une unité de mammographie mobile (MM) dans le dépistage du cancer du sein à partir de données rétrospectives (n=37461), 2) d’un accompagnement personnalisé (AP) («patient navigation») dans le dépistage du cancer colorectal à partir d’un essai contrôlé randomisé (n=16250). Résultats. Le coût incrémentiel par dépistage supplémentaire comparé au dépistage habituel était: 1) de 611€ [492-821] pour l‘invitation au MM (+3.8% [2,8-4,8], +23.21€ [22.64-23.78]), et 2) de 1212€ [872-1978] pour l‘AP (+3.3% [1.5-5.0], +39.70€). L’efficacité et l’efficience étaient plus importantes dans les zones défavorisées et dans les zones éloignées pour le MM, alors qu’elles étaient moins favorables dans les zones défavorisées pour l’AP. Conclusion. La MM et l’AP peuvent réduire les inégalités en étant plus efficient dans les zones éloignées et les zones défavorisées pour la MM, alors que pour y parvenir, l’AP devrait cibler les sujets défavorisés, bien que n’étant pas la stratégie la plus efficiente. Les recherches doivent être poursuivies pour déterminer les conditions optimales de l’intégration du MM dans le dépistage, et pour améliorer l’efficacité et l’efficience de l’AP, qui ne peut être recommandé en l’état pour l’instant
Background. Increasing participation in organized cancers screening and reducing social and geographical inequalities in participation represent a major public health issue. Objectives. To determine the costeffectiveness of 2 interventions aiming at increasing participation and reducing inequalities in organized cancer screening in France Methods. We conducted a cost-effectiveness analysis from the payer's perspective: 1) of an invitation to a mobile mammography unit (MM) unit for breast cancer screening from retrospective data (n = 37461), 2) of a patient navigation program (PN) for colorectal cancer screening from a randomized controlled trial (n = 16250). Results. The incremental cost per additional screen compared with usual screening was: 1) € 611 [492-821] for the invitation to the MM (+ 3.8% [2.8-4.8], + € 23.21 [22.64-23.78] ), and 2) of € 1 212 [872-1 978] for PN (+ 3.3% [1.5-5.0], + 39.70 €). Effectiveness and cost-effectiveness were greater in deprived areas and in remote areas for MM, whereas they were less favorable in deprived areas for PN. Conclusion. MM and PN can reduce inequalities while being more efficient in remote areas and in deprived areas for MM, while, to achieve this, PN should target deprived people, even if being not the most efficient strategy. Research needs to be pursued to determine the optimal conditions for MM integration in organized breast cancer screening, and to improve the effectiveness and cost-effectiveness of PN, which can not be recommended as experimented for now

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Rideau, Alexis. "Rôle de la protéine sécrétée OLFM4 dans la carcinogénèse colorectale et mammaire : importance du contexte cellulaire." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0071.

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De par leur incidence et un diagnostic tardif, les cancers du sein et du colon restent parmi les plus meurtriers en France. L’identification de marqueur précoce semble primordiale pour détecter rapidement ces maladies et ainsi améliorer la survie des patients. Le protéome de chaque stade du cancer du côlon a été identifié et quantifié par spectrométrie de masse. L’Olfactomedine-4 (OLFM4) a été définie comme un biomarqueur potentiel par sa présence dans le sérum et ses variations d’expression. Alors que cette protéine est surexprimée, au niveau du site tumoral primaire,uniquement dans les stades précoces du cancer colorectal, sa surexpression est maintenue dans le sang des patients tous stades confondus. Cette variabilité d’expression est également retrouvée dans le cancer du sein. L’OLFM4 est décrite comme un marqueur des cellules souches colorectales mais ses fonctions restent contradictoires. Selon le contexte cellulaire, nos travaux associent cette protéine sécrétée à l’établissement de propriétés de cellule souche cancéreuse comme la prolifération en faible adhésion et la formation de mammosphères. Elle facilite également le processus migratoire et la résistance à la chimiothérapie. De plus, des expériences in vivo ont confirmé le caractère protumoral de cette protéine. Nous avons également mis en évidence son implication dans la régulation de l’expression du facteur de transcription GLI1 de la voie Sonic Hedgehog et de protéines d’adhésion telle que l’E-Cadherine. Cette étude décrit le lien étroit entre l’induction d’un phénotype agressif et l’OLFM4 dont le dosage sérique permettrait une détection précoce de ces maladies
Through their high frequencies and the lack of early diagnosis, breast and colorectal cancer remain poor prognosis’ diseases. Therefor, the identification of early markers appears as crucial. The proteomic approach isone of the potential tools to identify these biomarkers as it enables the study of tumour cell lines or tissues amples. Indeed, proteins enriched from a shotgun proteomic approach can be identified and quantified by mass spectrometry. In a previous study, we have analysed the proteome of colorectal tumour at different stages and defined Olfactomedine-4 (OLFM4) as a potential biomarker. While OLFM4 expression is increased at primary tumoral site only in non-invasive stages, we have observed that OLFM4 isover expressed in the blood of patients regardless of the cancer stage. The same analysis was made on breast cancer patients. Although OLFM4 has been described as a stem cell marker, its functions remain unclear. In this study, we found that OLFM4 confers cancer stem cell properties. It acts as a regulator of proliferation in low adhesion conditions, migration, mammosphere formation and tumor growth. These abilities could be dependent of Sonic Hedgehog signalling pathway, especially of transcriptional factor GLI1, and regulation of adhesion proteins like E-cadherin. According to the cellular background, all these features highlight a close relationship between a potential biomarker and its involvement in the acquisition of an aggressive phenotype

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FERRAIOLI, DOMENICO. "Assessment and relevance of the putative DNA/RNA helicase Schlafen-11 in ovarian and breast cancer." Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/989355.

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Abstract in English Schlafen 11 (SLFN11) is a putative DNA/RNA helicase, first described for its role in thymocyte development and differentiation in mouse models [1]. SLFN11 is part of a family of proteins with various degree of homology across species, but intriguingly being consistently present only in vertebrates and especially in mammals. Recently the role of this putative DNA/RNA helicase, SLFN11, was causal association with sensitivity to DNA damaging agents, such as platinum salts, topoisomerase I and II inhibitors, and other alkylators in the NCI-60 panel of cancer cell lines.13 In the first study, we validate an anti-SLFN11 antibody in formalin-fixed paraffin-embedded (FFPE) high-grade serous ovarian carcinoma (HGSOC) samples, developing a immunohistochemistry (IHC) protocol in order to determinate the expression of SLFN11 in our series of HGSOC. Indeed, we tested and validated a reliable SLFN 11 antibody (Ab) in IHC choosing between two anti-SLFN11 Ab used normally for Western Blot (WB) in culture cell block (CCB) of ovarian carcinoma and in an independent series of HGSOCs tissue micro-array (TMA). For each case, we evaluated both the Intensity Score (IS) and the Distribution Score (DS) evaluating at least 300 cells. A Histological Score (HS) was obtained as follow: HS=IS x DS. Successively, we applied our protocol to a large case series of HGSOC samples to confirm our preliminary results. We found one antibody to be reliable in CCB and TMA series allowing to determinate clearly IHC expression of SLFN11. These results were confirmed in our large case series of FFPE HGSOC samples. Briefly, as for TMA independent series, we found that the HS for SLFN11 expression presents a normal distribution with a prevalent (≈ 60%) intermediate expression. Parallel SLFN11 was not expressed in practically 40% of cases that clinically corresponded to the platinum resistant patients in about 60% of cases (16/27). So, we believe that low IHC expression of SLFN 11 should be correlated to response to the platinum based chemotherapy. In the second study, we investigate the transcriptional landscape of SLFN11 in breast cancer performing a gene expression microarray meta-analysis of more than 7000 cases from 35 publicly available data sets. By correlation analysis, we identified 537 transcripts in the top 95th percentile of Pearson’s coef- ficients with SLFN11 identifying “immune response”, “lymphocyte activation”and “T cell activation” as top Gene Ontology enriched processes. Furthermore, we reported very strong association of SLFN11 with immune signatures in breast cancer through penalized maximum like-lihood lasso regression Finally, through multiple corresponde analysis we discovered a subgroup of patients, defined “SLF11-hot cluster”, characterized by high SLFN11 levels, estrogen receptor negativity, basal-like phenotype, elevated CD3D, STAT1 signature, and young age and using Cox proportional hazard regression, we characterized SLFN11 high levels, high proliferation index, and ER negativity as independent parameters for longer disease-free interval in patients undergoing chemotherapy. We believe that our work supports proof of concept that: i) A clear and specific role for SLFN11 in breast cancer, in likely connection with the immune system modulation in such disease entity, ii) a strong correlation between high SFLN 11 and specific molecular subtype of breast cancer (estrogen receptor negativity, basal-like phenotype).

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Wong, Christina Misa Linnan Laura. "An evaluation of recruitment and retention strategies among Asian American women in the National Breast and Cervical Cancer Early Detection Program." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,1017.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Health Behavior and Health Education, School of Public Health." Discipline: Health Behavior and Health Education; Department/School: Public Health.

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Papin-Lefebvre, Frédérique. "L’organisation du dépistage des cancers en France : éthique et droits des patients." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05D008.

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Selon l’OMS, le dépistage organisé s’appuie sur la participation volontaire des sujets qui sont recrutés dans la population, dans le cadre de campagnes de dépistage. En France, deux dépistages sont organisés par les pouvoirs publics : le dépistage du cancer du sein et le dépistage colorectal. L’objectif de cette thèse était d’étudier sous l’angle éthique et médicolégal, les programmes français de dépistage organisé des cancers.Les valeurs éthiques applicables aux programmes nationaux de dépistage font l’objet de recommandations européennes et sont déclinées en France, dans des cahiers des charges annexés aux textes juridiques mettant en œuvre les programmes de dépistage. D’autres textes de portée plus générale encadrent cette pratique en France.Détaillé dans un rapport publié par l’INCa, l’analyse éthique du programme de dépistage organisé du cancer du sein pointe la nécessité d’optimiser l’information des patientes et de renforcer la place et le rôle d’un professionnel de santé référent, de l’entrée dans le dépistage jusqu’à la sortie éventuelle vers la filière de soins.L’étude des préférences des médecins généralistes dans l’organisation du dépistage du cancer colorectal montre que les questions relatives à l’information du patient et aux modalités de recueil de son consentement, ainsi qu’au suivi des patients, jouent une véritable influence sur leur adhésion au programme, au regard du risque médicolégal
According to WHO, organized screening is based on the voluntary participation of subjects who are recruited into the population through screening campaigns. In France, two are organized by the government: breast cancer screening and colorectal cancer screening. The aim of this thesis was to study by an ethical and forensic approach, the French organized programs for cancer screening.Ethical values of national screening programs are subject to European recommendations. In France, they are available in documents attached to the legal texts implementing screening programs. Some others texts more general, frame this practice in France.Detailed in a report published by INCa, the ethical analysis of organized screening program for breast cancer points the need to optimize patients’ information and to strengthen the position and role of the referring health professional, from the entry in the screening to the eventual output to the care.The study of GPs’ preferences in the organization of screening for colorectal cancer shows that issues related to patient information and procedures for collecting of consent, as well as patient monitoring, play a real impact on their adherence to the program, in terms of forensic risk

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Thomas, Sarah Nichole. "Decisions to Seek and Share: A Mixed Methods Approach to Understanding Caregivers Surrogate Information Acquisition Behaviors." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1595545894518707.

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46

Morris, Eva. "The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast, colorectal and lung cancer patients." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414496.

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Espejo, Herrera Nadia Carminia 1983. "Nitrate exposure and cancer risk : evidence from European case-control studies." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/323894.

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Ingested nitrate is a precursor of N-nitroso compounds that are carcinogens in animals, with limited evidence in humans. The main objective of this thesis was to evaluate whether the exposure to nitrate through drinking water and diet is associated with carcinogenic effects in humans. This thesis has been conducted in the Centre for Research in Environmental Epidemiology (CREAL) from 2011 to 2015, under the supervision of Cristina M. Villanueva Belmonte PhD. The results of this thesis consists of a compilation of four scientific papers including: a) a descriptive study of nitrate levels in drinking water in Spain (paper I), and b) three large European case-control studies evaluating the risk of prevalent tumors (bladder, breast and colorectal) associated with nitrate exposure through drinking water and diet (papers II, III and IV). This document also includes a general introduction, a description of the methodology, an overall discussion of the results, conclusions and an appendix section.
El nitrato ingerido es un precursor de compuestos N-nitroso, que son carcinógenos en animales, con poca evidencia en humanos. El objetivo principal de esta tesis fue evaluar si la exposición a nitrato a través del agua de consumo y la dieta está asociada a efectos carcinogénicos en humanos. Esta tesis fue llevada a cabo en el Centro de Investigación en Epidemiología Ambiental (CREAL) entre 2011 y 2015, bajo la supervisión de Cristina M. Villanueva Belmonte PhD. La parte principal de esta tesis es una compilación de cuatro artículos científicos, que incluyen: a) un estudio descriptivo de los niveles de nitrato en agua de consumo en España (artículo I) y b) tres estudios caso-control que evaluaron el riesgo de tres tumores prevalentes (vejiga, mama y colorrectal), asociados con la exposición a nitrato a través del agua de consumo y la dieta (artículos II, III and IV). Este documento incluye también una introducción general, una descripción de los métodos, una discusión y conclusiones generales y una sección de anexos.

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Nordman, Ina IC Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "Surrogate endpoints of survival in metastatic carcinoma." Publisher:University of New South Wales. Clinical School - St Vincent's Hospital, 2008. http://handle.unsw.edu.au/1959.4/42791.

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In most randomised controlled trials (RCTs), a large number of patients need to be followed over many years, for the clinical benefit of the drug to be accurately quantified (1). Using an early proxy, or a surrogate endpoint, in place of the direct endpoint of overall survival (OS) could theoretically shorten the duration of RCTs and minimise the exposure of patients to ineffective or toxic treatments (2, 3). This thesis examined the relationship between surrogate endpoints and OS in metastatic colorectal cancer (CRC), advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A review of the literature identified 144 RCTs in metastatic CRC, 189 in advanced NSCLC and 133 in MBC. The publications were generally of poor quality with incomplete reporting on many key variables, making comparisons between studies difficult. The introduction of the CONSORT statement was associated with improvements in the quality of reporting. For CRC (337 arms), NSCLC (429 arms) and MBC (290 arms) there were strong relationships between OS and progression free survival (PFS), time to progression (TTP), disease control rate (DCR), response rate (RR) and partial response (PR). Correlation was also demonstrated between OS and complete response (CR) in CRC and duration of response (DOR) in MBC. However, while strong relationships were found, the proportion of variance explained by the models was small. Prediction bands constructed to determine the surrogate threshold effect size indicated that large improvements in the surrogate endpoints were needed to predict overall survival gains. PFS and TTP showed the most promise as surrogates. The gain in PFS and TTP required to predict a significant gain in overall survival was between 1.2 and 7.0 months and 1.8 and 7.7 months respectively, depending on trial size and tumour type. DCR was a better potential predictor of OS than RR. The results of this study could be used to design future clinical trials with particular reference to the selection of surrogate endpoint and trial size.

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Zhang, Yuan. "Circadian clocks and cancer : The implication of BMAL1 (brain and muscle Arnt-like protein-1) in colorectal and breast carcinoma development and treatment." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS422.

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BMAL1, une protéine centrale de l'horloge circadienne.L’inactivation de BMAL1 (BMAL1-KO) entraîne une perte complète de la rythmicité dans les horloges central et périphérique. Le travail de ma thèse se concentre sur le rôle du gène BMAL1 dans la développement et le traitement des cancers du sein et du côlon.1. Pharmacodynamique in vitro de l’Everolimus en fonction du temps d’administration malgré une horloge circadienne défectueuse ((Zhang et al., 2018) (Zhang, Levi and Chang, 2018)L’everolimus (EV) est un inhibiteur de la mTOR chez les mammifères et il est utilisé pour traiter le cancer du sein positif aux oestrogènes (ER+). Nous avons focalisé nos recherches sur la chronopharmacologie de l’Everolimus administré sur des cellules MCF-7 (ER+). Les MCF-7 présentent une oscillation circadienne de l’activité de mTOR sans mise en évidence d’une oscillation des gènes d’horloge. L’oscillation d’activité de mTOR induirait une oscillation de synthèse et/ou de phosphorylation de protéines importantes dans la progression de la phase G1, notamment la Cycline D1 et RB phosphorylée. Ces variations rythmiques des MCF-7 synchronisées expliquent la chrono-efficacité de l’Everolimus selon des temps différents d’administration.Ce travail a révélé que même dans un système de cellules cancéreuses dont l’horloge était perturbée, l'intégration d'autres rythmes cellulaires dans la chronothérapie pouvait augmenter l'efficacité du médicament. Ce principe peut être appliqué à des traitements du cancer pour optimiser la chronothérapie du cancer.2. Le Knockdown BMAL1 a déclenché différents destins de cellules du carcinome du côlon (CRC) en modifiant l'équilibre délicat entre les voies AKT / mTOR et P21 / P53 (Article soumis)Premièrement, nos résultats ont révélé que le knockdown BMAL1 par le shRNA (BMAL1-KD) avait déclenché une activation plus évidente de l’AKT / mTOR dans deux lignées cellulaires primaires (HCT116 et SW480) que une lignée métastatique de CRC, SW620. De plus, bien que les deux lignées cellulaires primaires de CRC aient présenté une augmentation significative de l'activité de l'AKT/mTOR, elles avaient des statuts différents de P53 (WT ou mutant). Dans ce contexte, les cellules SW480 BMAL1-KD avec P53 mutant présentaient une sénescence accrue, mais les cellules HCT116 BMAL1-KD avec P53 WT présentaient d’abord une apoptose transitoire, puis un taux de prolifération plus élevé.Ainsi, nos travaux ont révélé le rôle crucial de BMAL1 pour équilibrer un régulateur central du métabolisme AKT / mTOR et une voie de réponse au stress P53 / P21 dans des lignées cellulaires de CRC, ce qui met en évidence l’importance de BMAL1 dans le développement de CRC et la progression du vieillissement.3. BMAL1 renforce les propriétés épithéliales et diminue la chimiorésistance des cellules du CRC (article en préparation)La transition épithélo-mésenchymateuse (EMT) est un événement critique dans l'invasion et la métastase des carcinomes, y compris le CRC.Dans ce travail, nous avons étudié comment BMAL1 knockdown (Bmal1-KD) altère l’équilibre délicat entre les propriétés épithéliales et mésenchymateuse de trois lignées cellulaires de CRC (HCT116, SW480 et SW620).Après BMAL1-KD, la diminution de l’expression Twist, un facteur de transcription favorisé l’EMT et des marqueurs mésenchymateux (N-Cadhérine, Vimentine) étaient associées à une expression accrue des marqueurs épithéliaux (E-cadhérine, CK20 et EpCAM). De manière constante, l'augmentation de l'expression de l’E-cadhérine après BMAL1-KD était accompagnée d'une co-localisation membranaire accrue de la β-caténine avec l'E-cadhérine, ainsi que d'une diminution de la localisation nucléaire de la β-caténine, suggérant une diminution de l'activation de la voie Wnt. De plus, les cellules BMAL1-KD ont montré une diminution des capacités de migration et de la résistance aux médicaments.Au total, ces données soulignent l’importance de BMAL1 dans l’EMT des cellules de CRC
BMAL1 is a core circadian clock protein, forming a heterodimer with CLOCK to initiate the transcription of circadian and output genes. Among canonical clock genes, only BMAL1 knockout results in complete loss of rhythmicity in both the SCN and peripheral tissues. My thesis work focuses on exploring the important role of BMAL1 in human breast and colon cancer progression and treatment. My work is divided into three main parts:1. Dosing time dependent in vitro pharmacodynamics of Everolimus despite a defective circadian clock (Zhang et al., 2018)(Zhang, Levi and Chang, 2018) Everolimus (EV) is an inhibitor of mammalian target of Rapamycin (mTOR) and is used to treat estrogen positive (ER+) breast cancer. Here, we investigated whether EV efficacy varied according to administration timing by using the ER+ breast cancer cell line MCF-7 as a model system. Serum shock synchronization induced a circadian oscillation in mTOR activity in MCF-7 cells, which rhythmically regulated the synthesis or phosphorylation of key G1 progression proteins, such as Cyclin D1 and phosphorylated RB, ultimately resulting in different G0/G1 blockage efficiency according to different EV administration timing. Thus, the different delivery schedule of EV presented different efficacy in G0/G1 phase blockage in serum shocked MCF-7 cells.This investigation revealed that, even in a breast cancer cell system with disrupted circadian organization, modulating drug administration according to other protein rhythms could still increase drug efficacy. This principle may be applied to many other cancer systems and treatment types to optimize cancer chronotherapy.2. Knockdown BMAL1 triggered different colon carcinoma cells fates by altering the delicate equilibrium between AKT/mTOR and P21/P53 pathways (Article in preparation)We tried to evaluate in vitro how knockdown BMAL1 (BMAL1-KD) by shRNA influences human colorectal cancer cell (CRC) behavior.The results revealed that BMAL1-KD triggered different CRC cell fates based on distinct p53 status in different cell lines. First, after BMAL1 knockdown, two primary CRC cell lines (HCT116 and SW480) presented a more evident AKT/mTOR activation than the metastatic colon carcinoma cell line, SW620. Furthermore, although both primary CRC cell lines presented a significant increase of AKT/mTOR activity, they had different P53 status (WT or mutant) and activation pattern. Under these context, SW480 BMAL1-KD cells exhibited increased senescence but HCT116 BMAL1-KD cells showed firstly a transient apoptosis and then higher proliferation rate.Thus, our work uncovered the crucial role of BMAL1 to balance a central metabolism regulator AKT/mTOR and a stress response pathway P53/P21 in CRC cell lines, which highlighted the importance of BMAL1 in CRC development and aging progression.3. BMAL1 knockdown leans epithelial–mesenchymal balance toward epithelial properties and decreased the chemoresistance of colon carcinoma cell (Article in preparation)Epithelial-mesenchymal transition (EMT) is a critical early event in the invasion and metastasis of carcinoma, including colorectal cancer (CRC). In this work, we studied how BMAL1-KD alters the delicate equilibrium between epithelial and mesenchymal properties of three colon carcinoma cell lines (HCT116, SW480 and SW620).The results showed the molecular alterations after BMAL1-KD promote mesenchymal-to-epithelial transition-like changes mostly appeared in two primary CRC cell lines (HCT116 and SW480) compared to the metastatic cell line SW620. Subsequently, BMAL1-KD HCT116 and SW480 cells harbored a decreased migration, invasiveness and drug resistance capacities relative to their scramble counterpart cells. All these data suggested the importance of BMAL1 on EMT inducing in colon carcinoma cells

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Binneman, Brigitte. "Selective induction of apoptosis by 7- methyljuglone, its derivatives and isolated compounds from foeniculum vulgare Mill. on human cancer cells." Diss., Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-06112009-173251/.

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Дисертації з теми "Cancer (colorectal, breast, cervical)"

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