Breast cancer is the most common cancer in women. It is a highly heterogeneous disease in terms of histology, therapeutic response and patient outcomes. Early and accurate detection of breast cancer is crucial as the patient prognosis varies greatly depending on the diagnosis of the disease. Nonetheless current breast cancer classification methods fail to precisely sub-classify the disease, resulting in potential inadequate therapeutic management of patients and subsequent poor clinical outcomes. Substantial effort is therefore put in cancer research to develop methods and find new biomarkers efficiently identifying and characterizing breast tumor cells. Moreover it is now well-recognized that the intensive cross-talk between cancer cells and their microenvironment (including non-tumor cells) highly influences cancer progression. Recently, a growing body of clinical evidence reported the prognostic and predictive value associated with the presence of tumor infiltrating lymphocytes (TILs) in the microenvironment of breast tumors. Although the evaluation of TILs would be of great value for the management of patients and the development of new immunotherapies, it is currently not assessed in routine practice. Furthermore Fourier transform infrared (FTIR) imaging has shown its usefulness to study a panel of human cancers. Infrared (IR) spectroscopy coupled to microscopy provides images composed of multiple spectra reflecting the biochemical composition and subtle modifications within biological samples. IR imaging therefore provides useful information to improve breast cancer identification and characterization. The ultimate aim of this thesis is to improve breast cancer diagnosis using FTIR imaging to better identify and characterize cancer cells and the tumor microenvironment of breast cancers. In a first step we carried out a feasibility study aiming at evaluating the impact of the sample fixation process on IR spectra. While spectra were undeniably influenced by this biochemical alteration, our results indicated that closely-related cell types were influenced similarly and could still be discriminated on the basis of their spectral features. We then demonstrated the capability of IR imaging to discriminate a tumor from a normal tissue environment based on the spectral features of tumor cells and the surrounding extracellular matrix. A particular focus was placed on the identification of lymphocyte spectral signatures of cells isolated from blood or present within secondary lymphoid organs such as tonsils. Our results revealed that IR imaging was sensitive enough to discriminate lymphocyte subpopulations and to identify a particular spectral signature that we assigned to lymphocyte activation. Finally we highlighted the potential value of IR imaging as complementary tool to identify and characterize TILs in breast tumor samples. Altogether, our results suggest that IR imaging provides interesting and reliable information to improve breast cancer characterization and to assess the immune microenvironment of breast tumors.<p>/<p>Le cancer du sein est le carcinome le plus fréquent chez la femme. C’est une maladie très hétérogène du point de vue histologique, de la réponse thérapeutique et de l’évolution clinique. Une détection rapide et précise de la maladie est cruciale, un diagnostic du cancer du sein dès les premiers stades de la maladie permet une meilleure prise en charge du patient et est directement associé à un meilleur pronostic. Néanmoins la classification actuelle des cancers du sein ne permet souvent pas de caractériser la maladie de manière précise, ce qui donne lieu à la mise en place de traitements moins ciblés et une évolution clinique peu favorable. Pour remédier à cela, des efforts conséquents sont réalisés en recherche, dans le but de mettre au point des méthodes capables d’identifier et de caractériser les cellules tumorales. De plus il est actuellement reconnu que le micro-environnement tumoral (composé des cellules non-tumorales) influence fortement la progression du cancer. Récemment de nombreuses études ont montré que la présence de lymphocytes au niveau des tumeurs mammaires (TILs) était corrélée à un meilleur facteur pronostic et prédictif. Bien que l’évaluation des TILs soit de grande importance dans le cadre des immunothérapies, cet élément n’est actuellement pas pris en compte dans les analyses de routine. Par ailleurs, l’imagerie infrarouge par transformée de Fourier (FTIR) a démontré son utilité dans l’étude de plusieurs cancers humains. La spectroscopie infrarouge (IR) couplée à la microscopie fourni des images composées de multiples spectres qui reflètent la composition biochimique et les modifications dans les échantillons biologiques. De ce fait l’imagerie infrarouge procure des informations utiles pour améliorer l’identification et la caractérisation du cancer du sein. L’objectif général de cette thèse est d’améliorer le diagnostic du cancer du sein par imagerie FTIR pour mieux identifier et caractériser les cellules cancéreuses et le micro-environnement tumoral des tumeurs mammaires. Dans un premier temps nous avons effectué une étude de faisabilité afin d’évaluer l’impact du protocole de fixation des tissus sur les spectres IR. Bien que les spectres soient indéniablement influencés par cette altération biochimique, nos résultats indiquent que des types cellulaires proches sont influencés de manière similaire et peuvent donc être discriminés sur base de leurs caractéristiques spectrales. Nous avons ensuite démontré la capacité de l’imagerie IR de distinguer un environnement tumoral d’un environnement normal sur base des particularités spectrales des cellules tumorales et de la matrice extracellulaire. Une attention particulière a ensuite été portée afin d’identifier des signatures spectrales de cellules immunitaires du sang et au sein d’organes lymphoïdes secondaires, tels que les amygdales. Nos résultats ont révélé que l’imagerie IR permet d'identifier une signature spectrale particulière, que nous avons associée à une stimulation lymphocytaire. Finalement nous avons mis en évidence l’utilité de l’imagerie IR en tant qu’outil complémentaire pour identifier et caractériser les TILs dans les échantillons tumoraux mammaires. De manière générale, nos résultats suggèrent que l’imagerie IR fournit des informations intéressantes et fiables pour améliorer la caractérisation et l’évaluation du micro-environnement immunitaire dans les tumeurs mammaires. / Doctorat en Sciences agronomiques et ingénierie biologique / info:eu-repo/semantics/nonPublished

Le cancer est l'une des principales causes de décès dans le monde et reste une maladie difficile à traiter du fait des difficultés de pronostic, du développement rapide de métastases et de la résistance aux médicaments. Il en résulte une forte demande en méthodologies d'imagerie innovantes pour le diagnostic précoce et précis ainsi qu’en nouveaux agents anticancéreux possédant de nouveaux mécanismes pour surmonter la résistance aux médicaments. Le but de mon projet de recherche de doctorat était donc de contribuer à cet objectif.La première partie de ma thèse de doctorat a porté sur la création de systèmes sensibles et précis d'imagerie pour la détection de tumeurs cancéreuses en utilisant une nanotechnologie novatrice permettant la délivrance des agents d'imagerie spécifiquement dans les lésions tumorales. Nous avons conçu de nouveaux dendrimères amphiphiles pour assurer le transport de différents agents d'imagerie pour les imageries PET/SPECT, par résonance magnétique et par fluorescence optique. Ces systèmes d'imagerie ont été préparés soit par encapsulation de petites sondes d'imagerie à l'intérieur de nanomicelles dendritiques ou par fonctionnalisation de la surface hydrophile ou de la queue hydrophobe du dendrimère. La deuxième partie a eu pour objectif de développer de nouveaux agents anticancéreux possédant nouveaux mécanismes d’action et une meilleure activité antitumorale. A cet effet, nous avons conçu une série de nucléosides arylvinyltriazoles par réaction oxydante de Heck, ce qui nous a permis d'obtenir les composés désirés pourtant difficiles à synthétiser avec un très large éventail de substrats et une stéréosélectivité unique. / Cancer is one of the leading causes of death in the world, and remains a difficult disease to treat because of poor prognosis, rapid tumor metastasis and drug resistance. Therefore, innovative imaging modalities for early and precise diagnosis as well as new anticancer drug candidates with novel mechanisms to overcome drug resistance are in high demand. The aim of my PhD research project was to contribute to this goal.The first part of my PhD thesis was focused on establishing sensitive and precise imaging systems for cancer detection using innovative nanotechnology to deliver imaging agents specifically into tumor lesions. We designed and constructed novel amphiphilic dendrimers to carry different imaging agents for PET/SPECT imaging, magnetic resonance imaging and optical fluorescence imaging. These innovative imaging systems were prepared by either encapsulation of small imaging probes within the dendrimer nanomicelles, or functionalization of the dendrimer hydrophilic surface or hydrophobic tail. The second part of my PhD program aimed to develop new anticancer drug candidates with novel mechanisms for better anticancer activity. Therefore, we designed and synthesized a series of challenging arylvinyltriazole nucleosides via the oxidative Heck reaction, which allowed us to obtain the desired compounds with excellent substrate scope and unique stereoselectivity.

This thesis is part of the project undertaken to develop a diffusive acoustic confocal imaging system (DACI) that aims to differentiate between healthy and the diseased tissues in the prostate. Speed of sound is chosen as the tool to quantify the alterations in the tissues’ mechanical properties at different pathological states. The current work presents a scanning configuration that features three components: an acoustic emitter, a focusing mirror and a point receiver. The focusing mirror brings the collimated acoustic beam from the emitter into a focused probe position, which needs to be located within the bladder or at the near surface of the prostate. This position is introduced as the virtual source, where the acoustic intensity diffusively scatters into all directions and propagates through the specimen. The system design was simulated using ZEMAX and COMSOL to validate the concept of the virtual source. Lesions in a phantom prostate were found in the simulated amplitude and phase images. The speed of sound variation was estimated from the 1D unwrapped phase distribution indicating where the phase discontinuities existed. The measurements were conducted in a water aquarium using the tissue-mimicking prostate phantom. Two-dimensional projected images of the amplitude and the phase distributions of the investigating acoustic beam were measured. A USRP device was set up as the signal generation and acquisition device for the experiment. Two different signal extractions methods were developed to extract the amplitude and the phase information. The experimental results were found to generally agree with the simulation results. The proof-of-concept design was successful in measuring both the phase and the amplitude information of the acoustic signal passing through the prostate phantom. In future, the 2D/3D speed of sound variation needs to be estimated by an appropriate image reconstruction method. / Graduate / 2018-12-06

In cancer diagnosis there is a goal of having the treatment being tailored to each patient. This in order to increase efficiency and reduce side effects. Using more data on each patient can help in achieving this. One such data source is histological images on tissues, such as lymph nodes. This report sets out to find a method in which such images on lymph nodes can be automatically segmented. This so that they can later be analysed and maybe tell in what stage a cancer is in. Such work is today done by hand, and this makes it a subjective process, that might differ between doctors and institutions. If there was a method done by a computer, the process would be replicable and objective. Also, a lot of time would be saved. The results show that such a method is reachable in this early stage of development. It is also quite efficient when segmenting the lymph node itself. The segmentation of smaller areas of the lymph nodes is not as efficient, but with further work in the area it might improve enough to be useful. Some issues are still had since the method relies in part on a person to decide a parameter in order to get a clean segmentation. The final conclusion is that one model is to prefer compared to the others and that further work on this might make it a useful tool in analysing histological images.

This thesis discusses the research, experimental methods, and data gathered for the investigation of a novel method for the diagnosis of melanoma skin cancer. First, a background about human skin tissue is presented. Then, a detailed description of melanoma along with current diagnosis techniques and treatment options are presented. In the experimental methods, the electrical properties of several types of tissue were analyzed, the purpose of which was to discover if a tissue type can be distinguished by its electrical properties alone. This would allow for the diagnosis of melanoma to be done by examining the electrical properties of the suspected tumor and comparing the results to known values of healthy and cancerous skin. After analyzing the data, it was concluded that tissue types can be identified by their electrical properties and it may be possible to diagnose melanoma through this method. Finally, the possibility of using a similar technology and radiofrequency tissue ablation to treat melanoma is presented.

Background. While the prevalence of a pathogenic variant in the BRCA1 and BRCA2 genes occurs in about 1:400 (0.25%) in the general population, the prevalence is as high as 1:40 (2.5%) among the Ashkenazi Jewish population. Despite cost-effective preventive measures for mutation carriers, Orthodox Jews constitute a cultural and religious group that presents challenges to BRCA1 and BRCA2 genetic testing. This study analyzed a dialogue of key stakeholders and community members to explore factors that influence decision-making about BRCA1 and BRCA2 genetic testing in the New York Orthodox Jewish community. Methods. Qualitative research methods, based in Grounded Theory and Narrative Research, were utilized to analyze the narratives of key stakeholders and community members in an analysis of qualitative data collected from 49 stakeholders. A content analysis was conducted to identify themes; inter-rater reliability was 71%. Results. Facilitators to genetic testing were prevention and education, while barriers to genetic testing included negative emotions, impact on family/romantic relationships, cost, and stigma. The role of religious figures and healthcare professionals in medical decision-making were viewed as controversial. Education, health, and community were discussed as influential factors. There were issues around disclosure, implementation, and information needs. Conclusion. This study revealed the voices of the Orthodox Jewish women (decision-makers) and key stakeholders (influencers) who play a critical role in the medical decision-making process. The findings have broad implications for engaging community stakeholders within faith-based or culturally distinct groups to ensure better utilization of healthcare services for cancer screening and prevention designed to improve population health.

<p>Mass spectrometry (MS) can provide rapid, sensitive, and specific analysis, making it a valuable tool to characterize biomolecules, especially their dynamic changes when involved in significant processes.  Compared to other analytical techniques, which mostly focus on solution-phase or solid-phase characterization, MS enjoys a more general and efficient detection of gas-phase analytes since it ultimately measures abundances of bare ions in vacuum. This unique detection capability of MS has been demonstrated, in this dissertation, by characterizing the neutral serine octamer, a gas-phase amino acid cluster that has been detected by MS only so far. Besides its existence, the progress of chiral enrichment has also been monitored and quantified by MS during octamer formation. The acquired MS data is crucial to interpreting the mechanism of chiral enrichment achieved by serine octamer and might suggest its involvement in the prebiotic world to eventually achieve biohomochirality. The work also showcases the capability of detecting neutral compounds by MS, which breaks the stereotype that MS is exclusively an ion-based technique. </p> <p><br></p> <p>Besides process monitoring in the open air, MS also monitors the highly complicated metabolism processes inside biosamples, primarily benefiting from its excellent sensitivity, specificity, and throughput of ion detection. Since altered cellular metabolism is being recognized as a hallmark of cancer, MS is suitable for cancer diagnostics, whose performance of diagnosing glioma, a common brain cancer, has been tested.  Desorption electrospray ionization(DESI) has been used as it avoids sample preparation and allows direct characterization of raw tissue, therefore well suited for on-site analysis such as in the operating room. In short, we have applied intraoperative DESI-MS analysis on raw brain biopsies to provide glioma diagnostics within 5 min. Specifically, the molecular features revealed by MS are translated into pathological information of analyzed tissue, like genetic mutations and tumor concentrations, which is highly desired during surgeries to guide tumor resection and improve patient management. </p> <p><br></p> <p>Knowledge of diagnostic biomarkers is essential to the translation from MS data to pathology, which can be obtained by metabolic profiling using MS. Despite the tradeoff between comprehensive characterization and analysis time, we have extensively explored endogenous metabolites by using tandem MS and expedited analysis by avoiding the use of chromatography. After fast profiling, statistical analysis of all MS features has been applied to discover diagnostic markers to distinguish healthy brain tissue from cancerous tissue. DESI-MS methods have been developed to facilitate a simple and rapid characterization of these biomarkers in tissue for a smooth clinical transition. </p> <p><br></p> <p>However, the complete characterization of endogenous metabolites in a complicated biomixture, like tissue, is challenging, especially without the orthogonal separation provided by chromatography. This unmet demand calls for the development of novel MS scans to improve the metabolite coverage. For lipidomics by direct infusion MS, the MS scans used for lipid profiling have not been greatly expanded since its introduction. These conventionalMS scans only target one structural moiety of lipids and leave the rest unresolved, which limits the structure elucidation and biological interpretation of diagnostic lipids. We have introduced additional lipid scans that target both the lipid headgroup and one fatty acyl chain, leaving the other fatty acyl chain flexible. These scans with higher specificity can further alleviate the matrix effect by uncovering fewer ions in each scan and provide more structural information to support lipid identification. As a proof-of-concept, we have used them to profile both common phospholipids and the rarer ether lipids that display significant variations between healthy mice tissue and those with metabolic syndrome. The additional structural information provided by these scans ensures a clear message expressed by the disease metabolism and potentially indicates invention points and therapeutic candidates.</p>

A model was developed in this study to understand women's cervical screening behaviour. It revealed that the interaction among institutional factors, risk appraisal, coping appraisal, and health beliefs and cultural factors contributed to the complex nature of screening behaviour among Chinese women. The institutional component provided the contextual factors within which women perceived the risk of cervical cancer, perceived the practice of cervical screening, and decided to take or not to take cervical screening. Risk appraisal provided the premise factor that induces women to seek coping strategies to reduce or remove the risk. During the process of coping appraisal, women's motivation to have cervical screening could be increased or decreased as the perceived benefits and costs of screening interacted with each other. The importance of the women's health beliefs and cultural factors was reflected in the way that they were affected by their notions of health behaviour and their cultural beliefs about cervical cancer risk and cervical screening participation. Commitment to participate in screening was a reinforcing factor inducing women to take up an offer of cervical screening. / Aim: To explore the knowledge and the perception of the risk of cervical cancer, identify the factors determining cervical screening behaviour, and develop a model to understand cervical screening behaviour among women in mainland China. / Background: Cervical cancer is the most common type of cancer, and is the second most common cause of cancer death in women in mainland China. Cervical screening is the most important intervention for the secondary prevention of cervical cancer. Theories of health behaviour and empirical research highlight risk perception as a significant factor motivating people to opt for cancer screening. However, little is known about the risk perception of cervical cancer and the factors influencing the screening participation of women in mainland China. / Conclusion: This study provides evidence of the complex factors influencing cervical screening behaviour and contributes new knowledge to the understanding of cervical screening behaviour within the Chinese cultural context. It further informs programmes for the promotion of cervical screening among this population. / Methods: A mixed method design consisting of two phases was used, employing both quantitative and qualitative methods of data collection. First, a cross-sectional survey was conducted to collect a baseline assessment of women's knowledge of cervical cancer and screening, their perceptions of the risk of cervical cancer, and the relationship between these factors and their cervical screening behaviour. Findings from this phase also guided the purposive sampling of participants in phase two. / Results: The findings from phase one demonstrated that the availability of an organized screening programme was a major motivator for women to opt for cervical screening. Multivariate analysis shows that having children (OR=2.57, p=0.026), a perception that visiting doctors regularly is important for health (OR-2.66, p=0.025), average (OR-4.84, 1)=0.006) and high levels of knowledge about cervical screening (OR-9.66, p=0.001) were significantly associated with having been screened in the previous three years. / Then in phase two, qualitative research was conducted using semi-structured interviews of 27 women, 16 of whom had been screened and 11 had not. The interview structure was based on an initial analysis of the data from phase one and from a review of the related literature. The data from the interviews were analyzed using latent content analysis, involving an interpretative reading of the symbolism underlying the surface structure in the text. The audio recordings of the interviews were transcribed verbatim in Chinese, and then the key phrases which were important for the objectives of the study were identified. The key phrases and words were grouped according to their commonality of meaning. Then, these groups of data were sorted and classified to create categories and sub-categories, which were mutually exclusive, explicit and accurate without overlapping. / Two themes emerged from the qualitative data from phase two. Theme I was that perceptions of cervical cancer and cervical screening included five categories: the perceived effects of suffering from cervical cancer; the perception of cervical screening; a lack of understanding about cervical cancer and screening; the perceived risk of cervical cancer; and factors related to the cultural beliefs system. Theme II was that the institutional and health care practitioner system included two categories: availability of an organised physical examination programme and the role of the health care practitioner in encouraging cervical screening utilization. / Gu, Can. / Adviser: Chan, Carmen. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 244-267). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

This qualitative study explored and described the experience of African women diagnosed with both HIV/AIDS and cervical cancer in order to gain an understanding of the experience of both illnesses as lived by these women. Phenomenological research methods were employed using in-depth semi-structured interviews. Communication as a strategy facilitating diagnosis, disclosure, acceptance and support for women with HIV/AIDS and cervical cancer emerged as the main theme, followed by the experience of physical symptoms and emotional experiences. The study shows the importance of communication in the management and support of these women attending public health institutions and in the community. For communication to occur the relationship between healthcare professionals and women diagnosed with HIV/AIDS and cervical cancer is very important. Treatment approaches in radiation therapy need to be developed for women diagnosed with HIV/AIDS and cervical. More research is needed in this area (HIV/AIDS and cervical cancer). / Health Studies / M.A. (Public Health)

Shared characteristics and predictors of psychological distress are beginning to be identified in research on women seeking genetic testing for BRCA1 and BRCA2 gene mutations. This study further explored patterns of psychological distress for 51 community women waiting to receive such genetic test results. There was no significant relationship between psychological distress and family cancer history, personal cancer history, social support networks, and family environment. Women in this sample tended to rely more on females and relatives for support than males and friends. Social support satisfaction was not related to gender or number of relatives providing support. Thirty-four of the 36 women classified on the family environment type were from Personal Growth-Oriented families. Comparisons with normal and distressed family means revealed increased cohesion and expressiveness with decreased conflict, indicative of supportive family environments. Limitations and implications are discussed.