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CATTIER, JEAN-MICHEL. "Contribution a l'etude de l'anurie dans les cancers pelviens : cancer de prostate, cancer colo-rectal, cancer du col de l'uterus". Limoges, 1988. http://www.theses.fr/1988LIMO0208.
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Fruka, Tayra. "An evaluation of cancer biomarkers in normal ovarian epithelial cells and ovarian cancer cell lines". University of the Western Cape, 2019. http://hdl.handle.net/11394/6920.
Testo completoAbstract (sommario):
Philosophiae Doctor - PhDIntroduction: Globally, there are over 190,000 new reported cases of ovarian cancers per annum. This comprises 3% to 4% of all cancers in women. Ovarian cancer is one of the leading causes of deaths in women. Ovarian cancer is the second most diagnosed gynaecological malignancy and over all the fifth cause leading to death among all types of cancer in the UK in 2004. More than 70% of epithelial ovarian cancers are diagnosed at an advanced stage. Consequently, the prognosis is poor and the mortality rate high. Thus, the survival rate is affected by how far the disease has progressed or spread. A dire need exists to identify ovarian cancer biomarkers, which could be used as good indicators of expression in ovarian cancer cells in vitro Aim: The aim of this study was to analyse selected cancer biomarkers, which are currently under intense investigation for their suitability to diagnose epithelial ovarian cancer at an early stage. These biomarkers were analysed in terms of their in vitro expression in normal epithelial cells and ovarian cancer cell lines, which allows for their genomic and proteomic classification. The expression analysis of each biomarker is related to the malignancy of a tumour and, therefore, advocates its use for potential future improvement of sensitive tumour markers. Methods: The primary human ovarian surface epithelial cell line (HOSEpiC), SKOV-3 cells and the OAW42 human epithelial ovarian tumour cell lines were used to evaluate the selected cancer biomarkers. Cells were cultured using appropriate media and supplements, and real-time quantitative polymerase chain reaction (RT-PCR) utilized to validate expression levels of the following genes: HDAC1, HDAC2, HDCA3, HDAC5, HDAC6, HDAC7, HDAC8, LPAR1, LPAR2, MUC16 and FOSL1, against normal housekeeping genes GAPDH and HPRT. In addition, immunocytochemistry was also used in the validation process of the aforementioned genes. Significance: ovarian cancer cells express gene signatures, which pose significant challenges for cancer drug development, therapeutics, prevention and management. The present study is an effort to explore ovarian cancer biomarkers to provide a better diagnostic method that may offer translational therapeutic possibilities to increase five- year survival rate. Results: HDAC5, HDAC6, LPAR1, LPAR2 and MUC16 expressed distinctively in ovarian cancers matched to other tissues or cancer types have already been identified by RT-QPCR and confirmed by immunocytochemistry and efforts to generate monoclonal antibodies to the other six genes (HDAC1, HDAC2, HDAC3, HDAC7, HDAC8 and FOSL1) encoded proteins are underway. Conclusions: here we provide strong evidence suggesting that HDAC5, HDAC6, LPAR1, LPAR2, except MUC16 are up regulated in ovarian cancer. These data were confirmed by examining Human Protein Atlas (HPA) databases, in addition to protein expression of HDAC5, HDAC6, LPAR1, LPAR2 and MUC16 in cells cytoplasm. For future prospective, using other techniques that assess the variant expression that could explain the release of these gene candidates into the circulation with serum tumour markers, and protein expression will be strengthened.
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Engler, Jennifer [Verfasser]. "Cancer Care and Cancer Patients’ Experiences with Cancer / Jennifer Engler". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1180994191/34.
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Stocks, Tanja. "Metabolic factors and cancer risk : prospective studies on prostate cancer, colorectal cancer, and cancer overall". Doctoral thesis, Umeå universitet, Urologi och andrologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-22567.
Testo completoAbstract (sommario):
Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited. Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI). Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can. Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer. Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors. Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer. Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.
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Eberst, Guillaume Nicolas. "Seconds cancers après traitement curatif d'un cancer broncho-pulmonaire". Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. http://www.theses.fr/2023UBFCE029.
Testo completoAbstract (sommario):
Le premier des objectifs du plan cancer 2014-2019 était de guérir plus de malades en favorisant les diagnostics plus précoces. Cet objectif laisse espérer davantage de diagnostic à des stades précoces accessibles à une résection chirurgicale. A l’heure actuelle, la chirurgie exérèse d’un cancer broncho-pulmonaire non à petites cellules (CBNPC) est le traitement offrant le plus d’espoir de guérison. Ce travail de thèse s’intéresse tout particulièrement au devenir des patients opérés.Malgré une intention curatrice, les patients opérés d’un CBNPC sont à risque de récidive du cancer opéré mais ont également un risque de second cancer, et en particulier de second cancer broncho-pulmonaire primitif (SCBP), supérieur à celui de la population générale, de l’ordre de 20% d’incidence cumulée à 10 ans. Lorsque survient une lésion pulmonaire de même diagnostic histologique que le cancer opéré, le diagnostic différentiel entre récidive du cancer opéré ou SCBP est difficile. Plusieurs définitions existent. En se basant sur l’hypothèse que les récidives sont le témoin d’une agressivité de la maladie cancéreuse, et donc le plus souvent de plus mauvais pronostic que les deuxièmes cancers, nous avons conduit dans un premier temps une revue systématique Cochrane de l’ensemble des définitions utilisées dans la littérature afin d’identifier celle qui offre la meilleure distinction pronostique, sur laquelle se baser pour le diagnostic différentiel entre récidive du cancer opéré et SCBP.Il y a quelques années, l'immunothérapie s'est imposée dans l'arsenal thérapeutique du cancer broncho-pulmonaire. D'abord utilisée en situation métastatique, l'immunothérapie est maintenant testée en situation péri-opératoire dans de nombreux essais. Cependant, en raison de la diversité des combinaisons et des stratégies thérapeutiques, qui n'ont pas toutes été comparées entre elles, une incertitude demeure quant à la meilleure thérapie péri-opératoire pour les patients opérés d'un CBNPC de stade précoce. Nous avons initié une revue systématique d’essais interventionnels avec méta-analyse en réseau selon la méthode Cochrane portant sur l'efficacité de ces traitements péri-opératoires chez les patients atteints de cancer du poumon non à petites cellules.L’étude IFCT-0302 est la seule large étude randomisée de surveillance des opérés d’un CBNPC. Elle a inclus 1775 patients. Son objectif était de comparer la survie globale de deux stratégies de surveillance : par clinique et radiographies thoraciques dans le groupe contrôle, et par clinique, radiographies thoraciques et scanners thoraco-abdominaux dans le groupe expérimental. La qualité de vie décrite par le patient (QdV) est une mesure de trois domaines de la santé perçue : physique, social et émotionnel. La QdV est impactée par une condition médicale ou son traitement. L'évidence suggère que la chirurgie du cancer du poumon a un impact significatif sur la QdV. L’objectif de notre travail a été d’évaluer l’influence du type de surveillance sur la QdV dans la population de l’étude IFCT-0302.Lorsqu’une image pulmonaire anormale est détectée, son diagnostic histologique s’obtient fréquemment par ponction transthoracique guidée par le scanner. La principale complication du geste est le pneumothorax. Les contraintes hospitalières ne permettent pas d’hospitaliser tous les patients après une ponction transthoracique. Nous avons dans ce troisième axe, travaillé à la validation d’un score prédictif de survenue d’un pneumothorax retardé après une ponction-biopsie transpariétale pulmonaire scannoguidée, afin de sélectionner les patients qui doivent être surveillés en hospitalisation conventionnelle. Ce travail a été réalisé sur une cohorte de patients du CHU de Besançon, une partie de la cohorte ayant permis d’élaborer le score, l’autre de le valider. Enfin un travail de validation externe sur une cohorte de patients de l’Hôpital Bichat – Claude Bernard a été réaliséThe first objective of the 2014-2019 cancer plan was to cure more patients by promoting earlier diagnosis. This objective gives hope for more diagnosis at early stages accessible to surgical resection. Currently, excisional surgery for non-small cell bronchopulmonary cancer (NSCLC) is the treatment offering the most hope for a cure. This thesis work is particularly interested in the future of operated patients.Despite a curative intention, patients operated on for NSCLC are at risk of recurrence of the operated cancer but also have a higher risk of second cancer, and in particular second primary lung cancer (SPLC), higher than that of the general population. , of the order of 20% cumulative incidence at 10 years.When a lung lesion with the same histological diagnosis as the operated cancer occurs, the differential diagnosis between recurrence of the operated cancer or SPLC is difficult. Several definitions exist. Based on the hypothesis that recurrences indicate an aggressiveness of the cancerous disease, and therefore most often have a worse prognosis than second cancers, we first conducted a Cochrane systematic review of the set of definitions used in the literature in order to identify the one which offers the best prognostic distinction, on which to base the differential diagnosis between recurrence of operated cancer and SCBP.A few years ago, immunotherapy established itself in the therapeutic arsenal for bronchopulmonary cancer. First used in the metastatic situation, immunotherapy is now tested in the perioperative situation in numerous trials. However, due to the diversity of combinations and therapeutic strategies, not all of which have been compared with each other, uncertainty remains regarding the best perioperative therapy for patients undergoing surgery for early-stage NSCLC. We initiated a systematic review of interventional trials with network meta-analysis according to the Cochrane method on the effectiveness of these perioperative treatments in patients with non-small cell lung cancer.The IFCT-0302 study is the only large randomized surveillance study of NSCLC patients. It included 1775 patients. Its objective was to compare the overall survival of two monitoring strategies: by clinic and chest x-rays in the control group, and by clinic, chest x-rays and thoraco-abdominal scans in the experimental group. Patient-described quality of life (HRQoL) is a measure of three domains of perceived health: physical, social, and emotional. QoL is impacted by a medical condition or its treatment. Evidence suggests that lung cancer surgery has a significant impact on QoL. The objective of our work was to evaluate the influence of the type of surveillance on HRQoL in the population of the IFCT-0302 study.When an abnormal lung image is detected, its histological diagnosis is frequently obtained by transthoracic puncture guided by the scanner. The main complication of the procedure is pneumothorax. Hospital constraints do not allow all patients to be hospitalized after a transthoracic puncture. In this third axis, we worked on the validation of a predictive score for the occurrence of delayed pneumothorax after a CT-guided transparietal lung biopsy, in order to select patients who must be monitored in conventional hospitalization. This work was carried out on a cohort of patients from Besançon University Hospital, one part of the cohort having made it possible to develop the score, the other to validate it. Finally, external validation work on a cohort of patients from the Bichat – Claude Bernard Hospital was carried out
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Pieters, Huibrie. "From 'Cancer Patient' to 'Cancer Survivor' oldest breast cancer survivors in transition /". Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=2023818721&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Jégu, Jérémie. "Cancer ultérieur chez les survivants d'un premier cancer : incidence et impact sur la survie". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ006/document.
Testo completoAbstract (sommario):
Les objectifs de cette thèse étaient d’étudier les tendances du risque de second cancer primitif (SPC) selon l’année de diagnostic d’un premier cancer des voies aéro-digestives supérieures (VADS) dans le Bas-Rhin, de produire les premières estimations de l’incidence des SPC à l’échelle nationale en France et d’estimer la survie des patients atteints d’un cancer des VADS selon la présence d’antécédents de cancer. Ce travail a montré que : 1) L’excès de risque de SPC des VADS et de l’œsophage a diminué de 53% entre 1975 et 2006 dans le Bas-Rhin, mais que le risque de SPC du poumon est resté stable ; 2) Le risque de SPC en France est augmenté de 36% chez les patients atteints de cancer par rapport à la population générale ; 3) La survie des hommes atteints d’un cancer des VADS était fortement associée à la présence d’antécédents de cancer. Des perspectives se dégagent de ce travail en termes de recherche épidémiologique, de recherche clinique et de politiques de santé publiqueThe objectives of this PhD thesis were: to study the trends of the risk of second primary cancer (SPC) among patients with a head and neck (HNSCC) cancer in Bas-Rhin, to provide first nationwide estimates of the risk of SPC in France and to assess the survival of patients with a HNSCC depending on their history of cancer. This work showed that : 1) The excess risk of SPC of head and neck and esophagus sites decreased by 53% over three decades among patients with a HNSCC, and that the excess risk of SPC of the lung did not change significantly. 2) The risk of SPC among cancer survivors in France was increased by 36% compared to the general population. 3) History of cancer was strongly associated with survival among HNSCC patients. Several epidemiological and clinical research perspectives can be established based on this work. These results also present an interest in a public health perspective in the framework of the third cancer plan
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Soerjomataram, Isabelle. "Multiple primary cancers in patients with breast ans skin cancer". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10779.
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Almutairi, Mikhlid Hammad. "Identification of novel human cancer-testis-antigen genes in cancers". Thesis, Bangor University, 2014. https://research.bangor.ac.uk/portal/en/theses/identification-of-novel-human-cancertestisantigen-genes-in-cancers(015fda5b-5bd3-42c1-a610-811f0acde19a).html.
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陳潔盈 e Kit-ying Loucia Chan. "Expression analysis of Candidate cancer genes in non-small cell lung cancer". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011163.
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Roué, Tristan. "Épidémiologie des cancers en Guyane : Analyse des données du registre des cancers de Guyane". Thesis, Antilles-Guyane, 2014. http://www.theses.fr/2014AGUY0743/document.
Testo completoAbstract (sommario):
L'objectif du registre des cancers de Guyane est de collecter l ensemble des tumeurs invasives et/ou in situ survenues depuis le 1er janvier 2003 chez des patients vivant en Guyane, quels que soient la localisation de la tumeur, le lieu de diagnostic et de traitement. Cette thèse a pour but de décrire la population atteinte d un cancer afin d améliorer les connaissances sur cette maladie et ainsi de permettre aux actions de santé publique d être plus efficaces.De 2003 à 2009, le taux d incidence des cancers standardisé sur l âge était, dans les deux sexes, 30% inférieur en Guyane par rapport à la France métropolitaine et n était pas différent de celui d Amérique du Sud.Nous avons comparé l incidence, la mortalité et la survie relative des patientes atteintes d un cancer invasif du sein (CIS) et des patientes atteintes d un cancer invasif du col de l utérus (CIC) entre la Guyane et la métropole.Le ratio incidence/mortalité indiquait que les cancers du sein étaient de plus mauvais pronostic en Guyane par rapport à la métropole.La survie relative des femmes atteintes d un CIS était inférieure en Guyane par rapport à la France métropolitaine.En Guyane, le taux standardisé d incidence du cancer du col de l utérus était 4 fois plus élevé qu en métropole. Les femmes vivant dans l intérieur de la Guyane semblaient être diagnostiquées à un stade plus tardif et plus souvent sur symptômes que les femmes du littoral. L accès aux soins des migrants est un challenge et une source d inégalité de santé. La détection précoce des cancers à travers des programmes de prévention est cruciale pour améliorer la survie par cancer et notamment chez les patients étrangersThe objective of the cancer registry of French Guiana is to compile all patients living in French Guiana with malignant invasive pathology and/or in situ lesions starting January 1st 2003 in persons living in French Guiana, whatever the tumoral location and the place of diagnosis and care. This study aimed to describe the population with invasive cancer to improve the knowledge about this disease in order to target public health interventions more effectively.The age standardised incidence rate was 30% times lower than in France in both sexes and the same than in South America.We compared incidence and relative survival of patients with invasive breast cancer (IBC) and patients with invasive cervical cancer (ICC) between women from French Guiana and metropolitan France.The ratio between incidence and mortality showed that the prognosis of IBC in French Guiana was worse than in metropolitan France.The relative survival rate among women with IBC in French Guiana was lower than among women in metropolitan France.In French Guiana, the age-standardized incidence rate of cervical cancer was four times higher than in France. Women living in remote areas seemed to be diagnosed later and more often following symptoms.Access to care for migrants is challenging and sustains health inequalities. Early detection through prevention programs is crucial for increasing cancer survival notably for foreign-born patients. Further studies with more patients and other variables could improve the knowledge about these diseases
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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.
Testo completoAbstract (sommario):
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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Gharavi, Catherine. "Récidive après traitement conservateur pour cancer du sein : registre des cancers de Côte d'Or". Dijon, 1996. http://www.theses.fr/1996DIJOM038.
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Turner, Nicola Jane. "Cancer in older people : studies in lung cancer". Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399662.
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Coulson-Gilmer, Camilla Lucette. "Cancer stem cells and chemoresistance in ovarian cancer". Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/18470/.
Testo completoAbstract (sommario):
The high mortality rate associated with epithelial ovarian cancer (EOC) is due to its insidious onset, leading to late diagnosis as well as eventual development of chemoresistance in the majority of patients. Cancer stem-like cells (CSCs) are thought to contribute to development of multi-drug resistant (MDR) tumours partly through their high level of ABC-transporter expression, which enables them to survive chemotherapy. ABC-transporter (MRP1, MRP2, BCRP, Pgp) and putative CSC-marker (ALDH1A1, CD44) expression was therefore evaluated by immunohistochemistry in a paraffin-embedded cohort of 57 high-grade EOC tumours. Typically 9-12% of cells in tumours expressed CD44 / ALDH1A1. These may represent a population enriched for CSCs. ABC-transporters were expressed in 10- 43% of cells on average. Using Spearman rank test, there was no correlation between CSC- marker and ABC-transporter expression, however correlation was observed between many of the ABC-transporters, suggesting existence of highly drug-resistant populations within tumours. Expression of CA125 (a glycoprotein expressed by EOC cells and used clinically to detect EOC relapse) and EpCAM (a cell adhesion molecule expressed by EOC cells) was also investigated. Interestingly, patient tumours with the highest level of EpCAM had longer overall survival by Kaplan-Meier analysis. In addition, increased expression of MRP1 and CD44 predicted poorer patient outcome by Cox regression analysis. In vitro functional assays were also used to identify CSCs. Cells derived from ascites samples had a mean colony-forming efficiency (CFE) or 6.3%, and in unsorted tumours this was 11.4%. Cancer cells were then isolated from primary ascites and tumour samples (using CA125 and EpCAM). On average, self-renewing assays revealed a 2.2-2.4-fold increase in CFE for CA125 or EpCAM positive sorted cells compared to CA125 or EpCAM negative cells. Future studies could characterise these self-renewing populations, which may lead to identification of novel CSC targets for use in EOC treatment.
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Prokopishyn, Nicole Lesley. "Integrin Ã3ß1, cancer-associated glycans and colon cancer". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq23967.pdf.
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Zajac, Olivier. "Cancer associated fibroblasts stimulate cancer resistance to therapy". Electronic Thesis or Diss., Université Paris sciences et lettres, 2024. http://www.theses.fr/2024UPSLS001.
Testo completoAbstract (sommario):
Les patients atteints d'un cancer du rectum localement avancé reçoivent généralement une chimioradiothérapie à base de 5-FU et de radiation. Cependant, seulement 10 à 30 % d'entre eux obtiennent une réponse complète au traitement avec une excellente survie à long terme. En plus de la résistance inhérente des cellules cancéreuses au traitement, le microenvironnement de la tumeur semble jouer un rôle crucial dans a réponse tumorale. Les fibroblastes associés au cancer (CAFs), les cellules non cancéreuses prédominantes dans le cadre de la tumeur, sont organisés autour des cellules cancéruses et, avec la matrice extracellulaire (MEC) qu'ils produisent, forment une "capsule" autour de la tumeur. Nos études récentes indiquent que ces CAFs exercent des forces de compression sur les cellules cancéreuses, ce qui nous amène à émettre l'hypothèse que cette pression pourrait moduler la réponse des cellules cancéreuses au traitement.Pour étudier cela, nous avons développé un modèle de culture cellulaire en 3D mimant l'architecture tumorale, constitué de sphères tumorales englobées par dans du collagène I, peuplées de CAFs. De manière intéressante, nous avons découvert que la présence physique des CAFs augmentait la résistance des cellules tumorales au 5-FU, tandis que les molécules sécrétées par les CAFs avaient un impact limité. En utilisant des billes de polyacrylamide (billes PAA) comme substitut de forces de compression dans la même matrice de collagène 3D, nous avons constaté que les billes se réduisaient, suggérant une compression induite par les CAFs.En creusant davantage l'interaction entre les CAFs et les sphères tumorales, nous avons constaté que les CAFs se disposaient de manière similaire à ce qui est observé dans les échantillons de tumeurs réels, créant une structure de type capsule à la périphérie de la tumeur. En incorporant des billes PAA dans notre modèle et en inhibant la contractilité des CAFs, nous avons noté une réduction de la compression, laissant entendre un rôle actif des CAFs dans l'exercice de la pression. Nous avons étendu nos découvertes en traitant les sphères tumorales en présence de CAFs dont la capacité contractile de la myosine-IIA avait été réduite. De manière remarquable, la réduction de la capacité contractile des CAFs a restauré la sensibilité des cellules tumorales au 5-FU, mettant en évidence le rôle de la compression active induite par les CAFs dans la résistance au traitement.Pour tester si la pression est une cause directe de la résistance aux médicaments, nous avons comprimé des sphères cancéreuses en utilisant du dextran de poids moléculaire élevé en l'absence de CAFs. De manière intéressante, cette compression passive n'a pas modifié les niveaux de résistance des cellules tumorales. Ainsi, un puzzle est apparu : la compression statique via le dextran n'a pas conféré de résistance, tandis que la compression active par les CAFs est impliquée. Nous avons émis alors l'hypothèse que la différence réside dans la nature dynamique et cyclique de la compression induite par les CAFs. Pour confirmer cela, nous avons observé que les CAFs contractaient de manière dynamique le collagène-I, comme en témoigne leurs effets sur des piliers en PDMS. Nous avons conclu que la compression cyclique et oscillatoire exercée par les CAF pourrait être le facteur clé favorisant la résistance au traitementPatients with locally advanced rectal cancer typically receive chemoradiotherapy involving 5-FU and radiation. However, only 10-30% achieve a complete response with excellent long-term survival. Aside from the cancer cells' inherent resistance to treatment, the tumor microenvironment seems to play a crucial role in treatment outcomes. Cancer-associated fibroblasts (CAFs), the predominant non-cancer cells in the tumor setting, align themselves along the edges of the tumor, and together with the extracellular matrix (ECM) they produce, they form a 'capsule' around the tumor. Our recent studies indicate that these CAFs exert compression forces on cancer cells, leading us to hypothesize that this pressure could modulate how cancer cells respond to therapy.To investigate this, we developed a 3D cell culture model mimicking tumor architecture, consisting of tumor spheres embedded in collagen I, populated with CAFs. Interestingly, we discovered that the physical presence of CAFs increased the tumor cells' resistance to 5-FU, while molecules secreted by CAFs had a minimal impact. Using polyacrylamide beads (PAA-beads) as a proxy for compressive forces in the same 3D collagen matrix, we found that the beads shrunk, suggesting CAF-induced compression.Further probing into the interaction between CAFs and tumor spheres revealed that CAFs align similarly to what is seen in actual tumor samples, creating a capsule-like structure around the tumor periphery. By incorporating PAA beads in our model and inhibiting CAF contractility, we noted reduced compression, hinting at an active role of CAFs in exerting pressure. We extended our findings by treating tumor spheres in the presence of Myosin-IIA-depleted CAFs. Remarkably, reducing CAF contractile ability restored the tumor cells' sensitivity to 5-FU, underscoring the role of active CAF-induced compression in therapy resistance. To test if pressure is a direct cause of drug resistance, we compressed cancer spheres using high molecular weight dextran in the absence of CAFs. Interestingly, this passive compression didn't alter the tumor cells' resistance levels. Thus, a puzzle emerged: static compression via dextran didn't confer resistance, whereas active compression by CAFs did. We hypothesized that the difference lies in the dynamic, cyclic nature of CAF-induced compression. Confirming this, we observed that CAFs contract collagen-I dynamically, as evidenced by their effect on PDMS pillars. We concluded that the cyclic, oscillatory compression exerted by CAFs may be the key factor in promoting treatment resistance
18
Nicolle, Rémy. "Regulatory networks driving bladder cancer". Thesis, Evry-Val d'Essonne, 2015. http://www.theses.fr/2015EVRY0009/document.
Testo completoAbstract (sommario):
La carcinogénèse est une conséquence de la continuelle activation de la prolifération cellulaire. Dans les cellules normales, les signaux mitogéniques sont traités par un réseau complexe d’interactions protéiques et de réactions enzymatiques, appelées voies de signalisation. Dans certains cas, le signal peut induire l’activation de nouveaux gènes et ainsi déclencher la mitose. Lors du développement ou de la cicatrisation, cette régulation du phénotype cellulaire contrôle étroitement le nombre et le comportement des cellules contribuant ainsi au maintien d’un tissu fonctionnel sain. A partir de profils génomiques, transcriptomiques et protéomiques de tumeurs de la vessie ainsi que des transcriptomes de cellules urothéliales normales dans différents états de prolifération et de différenciation, j’ai mis au point de nouvelles méthodologies pour caractériser les voies de signalisation et de régulation responsables des cancers de la vessie. Dans un premier temps, j’ai développé des outils pour l’identification et la visualisation des programmes transcriptionnels spécifiques à une tumeur ou à un sous-type tumoral et ce, par l’inférence d’un réseau de co-régulation et la prédiction de l’activité des facteurs de transcription. Ces méthodes sont disponibles dans un package Bioconductor, CoRegNet (bioconductor.org). La mesure de l’activité transcriptionnelle est basée sur l’influence d’un facteur de transcription sur l’expression de ses gènes cibles. Cette mesure a été utilisée pour identifier les régulateurs les plus actifs de chaque sous-type de cancer de la vessie. L’intégration de profils génomiques a mis en avant deux facteurs de transcription génétiquement altérés et ayant des rôles oncogènes dans les tumeurs luminales et basales. L’un d’entre eux a été validé expérimentalement dans ce travail.L’utilisation de CoRegNet a mis en évidence une large utilisation dans les tumeurs,des réseaux normaux de la différenciation et de la prolifération des cellules normales. Un régulateur de la prolifération normale est identifié comme étant activé de fa¸con constitutive par des altérations génétiques dans les tumeurs. Son impact sur la prolifération des cellules tumorales de la vessie a été expérimentalement validé. Par ailleurs, il a été constaté que l’un des régulateurs de la différenciation urothéliale présentant une baisse d’activité dans la quasi-totalité des tumeurs, est fréquemment muté. De plus amples analyses ont mis en avant son rôle majeur dans les tumeurs différenciées. Dans le but de caractériser les voies de signalisation à partir de données protéomiques d’expériences d’immunoprécipitations, j’ai développé un nouvel algorithme visant à construire un réseau dense à partir d’une liste de protéines d’intérêt et d’un ensemble d’interactions protéiques connues. L’algorithme est proposé sous la forme d’une application Cytoscape et s’intitule Pepper: Protein Complex Expansion using Protein-Proteininteraction networks (apps.cytoscape.org) Enfin, en utilisant à la fois le profil protéomique d’une expérience d’immunoprécipitation de FGFR3 ainsi que le profil transcriptomique des gènes qu’il régule en aval, j’ai appliqué Pepper pour caractériser la voie de signalisation de FGFR3 depuis ses partenaires protéiques jusqu’aux facteurs de transcription en aval. Enfin, ce travail a plus particulièrement permis d’identifier un lien de régulation entre FGFR3 et le gène suppresseur de tumeurs TP53Carcinogenesis is a consequence of the unceasing activation of cell proliferation. In normal cells, mito-genic stimuli are processed by a complex network of protein interactions and enzymatic reactions, often referred to as pathways, which can eventually trigger the activation of new genes to engage the cell into mitosis. During developmental or wound healing processes, this complex regulation of cellular phenotypes results in a tight control of the number and behavior of cells and therefore contributes to the maintenance of a functional and healthy tissue architecture. Based on genomic, transcriptomic and proteomic profiles of bladder tumors and transcriptomes of nor-mal urothelial cells at various states of proliferation and differentiation, I devised novel methodologies to characterize the pathways driving bladder cancer. I first developed a set of tools to identify and visualize sample and subtype-specific transcriptional pro-grams through the inference of a co-regulatory network and the prediction of transcription factor activity. These methods were embedded in a Bioconductor package entitled CoRegNet (bioconductor.org). The measure of transcriptional activity is based on the influence of a transcription factor on the expression of its target genes and was used to characterize the most active regulators of each bladder cancer subtypes. The integration of genomic profiles highlighted two altered transcription factors with driver roles in lumi-nal-like and basal-like bladder cancer, one of which was experimentally validated. The use of CoRegNet to model the contribution of regulatory programs of normal proliferation and diffe-rentiation in bladder cancers underlined a strong preservation of normal networks during tumorigenesis. Furthermore, a regulator of normal proliferation was found to be constitutively activated by genetic al-terations and its influence on bladder cancer cell proliferation was experimentally validated. In addition, a master regulator of urothelial differentiation was found to have a loss of activity in nearly all tumors. This was then associated to the discovery of frequent inactivating mutations and further analysis unco-vered a major role in differentiated tumors. In order to characterize signaling pathways from proteomic pull-down assays, I then designed a novel algorithm to grow a densely connected network from a set of proteins and a repository of protein interac-tions. The proposed algorithm was made available as a Cytoscape application named Pepper for Protein Complex Expansion using Protein- Protein interaction networks (apps.cytoscape.org). Finally, using both a proteomic pull-down assay of the bladder cancer oncogene FGFR3 and a transcrip-tomic profiling of its downstream regulated genes, I applied Pepper to characterize the full FGFR3 signa-ling pathway from its protein partners to the downstream transcriptional regulators. In particular, this uncovered a regulatory link between FGFR3 and the tumor suppressor TP53
19
Simons, Jean Paul François Henri Auguste. "Cancer cachexia". Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5927.
Testo completo
20
Dadi, C. N. "Cancer immunotherapy". Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/40532.
Testo completoAbstract (sommario):
Over the years we have resorted to radiation, chemotherapy
and surgery in fighting cancer. Unlike the latter mentioned forms of
therapy cancer immunotherapy is one of the more recent approaches.
Cancer immunotherapy focuses on enhancing the body‘s immune
system in fighting cancer.
21
Holt, Jim. "Prostate Cancer". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6456.
Testo completo
22
Turner, Michelle Catherine. "Allergy and cancer: Analysis of the American Cancer Society Cancer Prevention Study II prospective cohort". Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26788.
Testo completoAbstract (sommario):
The presence of allergy may reduce cancer risk. Literature searches identified 142 epidemiological studies on this association. Data from the American Cancer Society Cancer Prevention Study-II cohort were used to explore the relationship between self-reported asthma and/or hay fever and cancer mortality in 508 318 men and 483 079 women who were cancer-free at baseline. During 18 years of follow-up from 1982--2000, there were 44 524 cancer deaths in men and 36 567 in women. Cox proportional hazards models were used to obtain adjusted relative risks for overall cancer mortality and for cancer mortality at 12 sites. There was approximately a 10% reduction in overall cancer mortality among people with asthma and hay fever. Asthma and/or hay fever were also associated with a reduced risk of cancer at a number of other sites, and some of the associations were modified by gender and smoking status.
23
Zucchero, Renee A. "Marital adjustment of older adult couples with breast cancer, prostate cancer, and couples without cancer". Virtual Press, 1998. http://liblink.bsu.edu/uhtbin/catkey/1117099.
Testo completoAbstract (sommario):
The purpose of this study was to explore the marital adjustment of older adult couples with breast cancer, prostate cancer, and couples who have experienced neither. Participants were 64 couples in which at least one of the spouses was over 55 years of age, including 19 breast cancer couples, 20 prostate cancer couples, 25 couples who had experienced neither of these cancers. Most participants were young-old, Protestant, Caucasians from a high socioeconomic class. The breast cancer and prostate cancer participants had completed treatment an average of 39.5 months prior to participation. The methodology was a mail survey. Participants completed a demographic questionnaire, the Marital Satisfaction Questionnaire for Older Adults (MSQFOP) (Haynes et al., 1992), Primary Communication Inventory (PCI) (Navran, 1967), Miller Social Intimacy Scale (MSIS) (Miller & Lefcourt, 1982), and the Index of Sexual Satisfaction (ISS) (Hudson et al., 1981).There were no differences in the amount of discordance between the couples groups' level of marital satisfaction, communication, intimacy, and sexual satisfaction. In addition, there were no differences in the level of marital satisfaction, communication, intimacy, and sexual satisfaction between the participant groups. There was a significantly greater correlation between the prostate cancer couples' scores on the ISS than the correlation between the breast cancer couples' scores and the scores of the couples who had not experienced breast cancer or prostate cancer.The level of marital satisfaction, communication, intimacy, and sexual satisfaction reported was similar to that of the normative samples. There was no difference between the marital adjustment of the cancer couples and older couples who had experienced neither type of cancer. These results are good news for breast and prostate cancer survivors, and professionals. Older adults may be better able to incorporate the experience of cancer into their lives or are better prepared for chronic illness through anticipatory socialization. The high degree of agreement between the prostate cancer spouses on the ISS may be related to the sexual dysfunction that frequently accompanies treatment for this cancer. Future research should be qualitative and longitudinal and continue to explore the psychosocial implications of prostate cancer.Center for Gerontology
24
Ninalga, Christina. "Cancer Immunotherapy : A Preclinical Study of Urinary Bladder Cancer". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6761.
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25
Li, Xinjun. "Familial risks for cancer with reference to lung cancer /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-007-9/.
Testo completo
26
Wu, Tsung-Jung. "Integration of Cancer-Related Mutations for Pan-Cancer Analysis". Thesis, The George Washington University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1556905.
Testo completoAbstract (sommario):
Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated sequence feature database, provides a framework for automated and manual curation and integration of cancer-related sequence features so that they can be used in NGS analysis pipelines. Sequence feature information in BioMuta is collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, UniProtKB and through biocuration of information available from publications. Additionally, nsSNVs identified through automated analysis of NGS data from TCGA are also included in the database. Due to the petabytes of data and sequence information present in NGS primary databases, a High-performance Integrated Virtual Environment (HIVE) platform for storing, analyzing, computing and curating NGS data and associated metadata has been developed. Using HIVE, 31,979 nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All variations identified through this process are stored in a Curated Short Read archive, and the nsSNVs from the tumor samples are included in BioMuta. Currently, BioMuta has 26 cancer types with 13,896 small scale and 308,986 large scale study-derived variations. Integration of variation data allows identifications of novel or common nsSNVs that can be prioritized in validation studies.
27
Ji, Jia. "Translational Research in Cancer: Preclinical Pharmacodynamics and Cancer Epidemiology". The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1250092164.
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28
Bebek, Gurkan. "Functional Characteristics of Cancer Driver Genes in Colorectal Cancer". Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1495012693440067.
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29
Pagotto, Anna. "Functional analysis of cancer/testis antigens in human cancer". Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711647.
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30
Revi, Bhindu. "Novel approach to cancer therapeutics using comparative cancer biology". Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/28996.
Testo completoAbstract (sommario):
Developing personalized cancer therapies based on cancer genomics methodologies forms the basis for future cancer therapeutics. A genomics platform was developed based on canine cancer to produce a proof-of-concept for personalized genomics led therapeutic choices but also developing personalized therapeutics for canine cancer patients themselves. The platform identified the genetic state of a canine cancer patient within two drugable pathways; p53 and HSP90/IRF1. The former gene was wild-type p53 thus directing the use of p53 activating molecules. The latter mutations in both HSP90 and IRF1 suggested an investigation into HSP90 and interferon signalling molecules as drug leads. Drugs that target both of these pathways were subsequently used to measure drug effects in cell line models but also to identify novel biomarkers of drug responses. My study focused on the effect of the HSP90-inhibitor Ganetespib had on its client proteins, particularly IRF-1. Briefly my results indicated the following:(i) Ganetespib downregulated IRF-1 protein levels in A375 cell lines and this attenuation was not mediated by either MDM2 or CHIP (E3 ligase). IFNγ- induced IRF-1 was also observed to be downregulated when Ganetespib was used in combination therapy.(ii) Insitu proximity ligation assay showed induced HSC70 upregulation upon HSP90 inhibition by Ganetespib and HSC70/MDM2 complexes were seen to be stabilized compared to the usage of MDM2/p53 inhibitor-nutlin. I hypothesize that MDM2/HSC70 complex might chaperon IRF-1 into lysosome for degradation via chaperon mediated autophagy pathway. (iii) My results also indicate that Ganetespib can downregulate IFN γ- induced PDL-1 expression in melanoma cell lines. Pre-sensitizing the cells with Ganetespib prior to the addition of IFNγ could attenuate PDL-1 to basal levels. (iv) My results also showed that the downregulation of PDL-1 by Ganetespib is an IRF-1 dependent mechanism. Therefore, my results suggest that HSP90 represents an important emerging target for cancer therapy because its inactivation results in the simultaneous blockade of multiple signalling pathways and can also sensitize tumor cells to other anticancer agents. Targeting HSP90 could also help to disrupt PD1/PDL- 1 interaction and activate immune system to recognise tumor cells. I conclude that HSP90 and IRF-1 play a critical role in types II interferon pathways and these findings establish a novel basis for the design of future Ganetespib-based combinatorial approaches to improve patient outcomes in this disease. These approaches finally demonstrate that cancer genomics can stratify choice of cancer drugs used on patients but also provide evidence that cancer patient samples can be used for the specific stratification of cancer drug choice based on cancer genomics data.
31
Li, Xing. "Novel brachytherapy techniques for cervical cancer and prostate cancer". Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/1682.
Testo completoAbstract (sommario):
Intensity-modulated brachytherapy techniques, compensator-based intensity modulated brachytherapy (CBT) and interstitial rotating shield brachytherapy (I-RSBT), are two novel conceptual radiation therapies for treating cervical and prostate cancer, respectively. Compared to conventional brachytherapy techniques for treating cervical cancer, CBT can potentially improve the dose conformity to the high-risk clinical target volume (CTV) of the cervix in a less invasive approach. I-RSBT can reduce the dose delivered to the prostate organ at risks (OARs) with the same radiation dose delivered to the prostate CTV. In this work, concepts and prototypes for CBT and I-RSBT were introduced and developed. Preliminary dosimetric measurements were performed for CBT and I-RSBT, respectively.
A CBT prototype system was constructed and experimentally validated. A prototype cylindrical compensator with eight octants, each with different thicknesses, was designed. Direct metal laser sintering (DMLS) was used to construct CoCr and Ti compensator prototypes, and a 4-D milling technique was used to construct a Ti compensator prototype. Gafchromic EBT2 films, held by an acrylic quality assurance (QA) phantom, were irradiated to approximately 125 cGy with an electronic brachytherapy (eBT) source for both shielded and unshielded cases. The dose at each point on the films were calculated using a TG-43 calculation model that was modified to account for the presence of a compensator prototype by ray-tracing.
With I-RSBT, a multi-pass dose delivery mechanism with prototypes was developed. Dosimetric measurements for a Gd-153 radioisotope was performed to demonstrate that using multiple partially shielded Gd-153 sources for I-RSBT is feasible. A treatment planning model was developed for applying I-RSBT clinically. A custom-built, stainless steel encapsulated 150 mCi Gd-153 capsule with an outer length of 12.8 mm, outer diameter of 2.10 mm, active length of 9.98 mm, and active diameter of 1.53 mm was used. A partially shielded catheter was constructed with a 500 micron platinum shield and a 500 micron aluminum emission window, both with 180° azimuthal coverage. An acrylic phantom was constructed to measure the dose distributions from the shielded catheter in the transverse plane using Gafchromic EBT3 films. Film calibration curves were generated from 50, 70, and 100 kVp x-ray beams with NIST-traceable air kerma values to account for energy variation.
In conclusion, CBT, which is a non-invasive alternative to supplementary interstitial brachytherapy, is expected to improve dose conformity to bulky cervical tumors relative to conventional intracavitary brachytherapy. However, at the current stage, it would be time-consuming to construct a patient-specific compensator using DMLS, and the quality assurance of the compensator would be difficult. I-RSBT is a promising approach to reducing radiation dose delivered to prostate OARs. The next step in making Gd-153 based I-RSBT feasible in clinic is developing a Gd-153 source that is small enough such that the source, shield, and catheter all fit within a 16 guage needle, which has a 1.65 mm diameter.
32
Walker, Meagan. "Assessment of Cancer-Related Fatigue in Breast Cancer Survivors". ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7348.
Testo completoAbstract (sommario):
Cancer-related fatigue (CRF) is a persistent and debilitating problem for many breast cancer survivors. Although many CRF measurement tools are available, no consensus exists on the most appropriate tool to use for breast cancer survivors. The purpose of this project was to identify the best method of assessing CRF in breast cancer survivors. The practice-focused question inquired about the most appropriate way to assess fatigue in breast cancer survivors. The central concepts of the project were CRF and cancer survivorship. This project was informed by the theory of health as expanding consciousness and Mishel's theory of uncertainty in illness. The sources of evidence included multi-database searches and literature from professional organizations. Results were tracked using preferred reporting items for systematic reviews and metasystems and a literature review matrix. The search identified 14 sources, which were assessed for quality using the grading of recommendations, assessment, development, and evaluation process. The results of this systematic review did not support the use of any particular assessment tool; however, 2 clinical practice guidelines recommended screening using a numerical severity scale followed by detailed assessment of clinically significant fatigue using available assessment tools. Screening can be implemented into the survivorship clinic, allowing nurses to identify potentially clinically significant fatigue so that further workup is done and interventions are implemented. Identifying, assessing, and intervening for clinically significant fatigue can improve the quality of life for breast cancer survivors, contributing to positive social change.
33
Haffey, Kerry Elaine Buckhalt Joseph Archie. "The relationship between emotional intelligence and psychological adjustment in children with cancer". Auburn, Ala., 2006. http://repo.lib.auburn.edu/2006%20Fall/Dissertations/HAFFEY_KERRY_22.pdf.
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34
Sridhar, Gayathri. "Meta-analysis: Racial Disparities in Prostate Cancer Survival and Case-Control Study: Association between Family History of Cancers, Obesity and Prostate Cancer". VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1758.
Testo completoAbstract (sommario):
This is a compilation of 3 abstracts for the three manuscripts included in this dissertation. I. Meta-Analysis: Racial Disparities in Prostate Cancer Survival: Prostate cancer is the second leading cause of cancer-related mortality in men. Previous studies have drawn inconsistent conclusions on racial differences in prostate cancer survival. This meta-analysis was conducted to investigate the relationship between race and survival from prostate cancer. A systematic review of published articles from 1968 to 2007 assessing survival from prostate cancer among African American and White men was conducted. The search yielded 20 eligible published manuscripts. Analysis of unadjusted studies showed African American men have an increased risk of all-cause mortality (Hazard ratio (HR) = 1.47, 95% confidence interval (CI): 1.31, 1.65, P < 0.001). However, examination of adjusted studies showed no difference (HR = 1.07, 95% CI: 0.94, 1.22, P = 0.308). No statistically significant difference was observed in prostate cancer-specific survival in both analyses using unadjusted (HR = 1.11, 95% CI: 0.94, 1.31, P = 0.209) and adjusted studies (HR = 1.15, 95% CI: 0.95, 1.41, P = 0.157). There was evidence of heterogeneity that was unexplained by factors analyzed in overall survival but explained by stage in prostate cancer-specific survival. This meta-analysis concludes that there are no racial differences in the overall and prostate cancer-specific survival between African American and White men. II. Case-Control study: Association between Family History of Cancers and Prostate Cancer: Family history of prostate cancer is an established risk factor for prostate cancer. However, the relationship between family history of cancers other than prostate cancer and prostate cancer risk is inconclusive. This study sought to examine the association between family history of cancers and prostate cancer. A case-control study was conducted in which cases and controls were randomly selected from a large urology clinic in Central Virginia. Cases were 600 histologically confirmed prostate cancer patients who were diagnosed between January 2000 and December 2005, and controls were 686 patients who visited the clinic during the same period and diagnosed with urological illnesses other than cancers and prostate-related problems. Data on family history of cancers, lifestyle and demographic factors were collected. Unconditional logistic regression analysis was used to estimate the odds ratios and the corresponding 95% confidence intervals after adjustment for potential confounding factors. Multiple comparisons adjustments were made using Bonferroni adjustment. Men with family history of any cancer in first-degree relatives including parents (OR=2.42, 95% CI: 1.53, 3.84) and parents only (OR=1.90, 95% CI: 1.23, 2.94) were at increased risk of developing prostate cancer compared to men with no such family history of cancer. Significant increased risk was also observed with family history of prostate cancer in first-degree relatives (OR=2.68, 95% CI: 1.53, 4.69) and parents only (OR=3.26, 95% CI: 1.71, 6.24) compared to men with no family history of prostate cancer. Even after adjustments for multiple comparisons, the significance persisted both in first-degree relatives (OR=2.68, 95% CI: 1.16, 6.21) and parents alone (OR=3.26, 95% CI: 1.24, 8.63). No association was found with family history of other cancers including breast, colon, lung, skin, digestive tract, stomach, liver, pancreas, female cancers, urogenital, urinary bladder, brain, blood and lymph node and other cancers and risk of prostate cancer. This study demonstrated an increased prostate cancer risk for men with a family history of any cancer or prostate cancer in first-degree relatives including parents and parents alone. Health care providers need to be aware of the potential risk of family history of cancers on prostate cancer. III. Case-Control study: Association between Obesity and Prostate Cancer: Obesity is a major public health problem in the United States. Several studies have investigated the association between obesity and prostate cancer risk. However the impact of early-adult obesity on prostate cancer is not well studied. This study proposes to investigate the relationship between prostate cancer and early-onset obesity and current obesity. A case-control study was conducted to investigate the relationship between obesity and prostate cancer in a large urology clinic population in Central Virginia. Cases included histologically confirmed prostate cancer patients of all stages and grades diagnosed from January 2000 to December 2005. Controls were patients who were diagnosed with urological illness other than cancers and prostate-related problems. Self-reported data was collected on anthropometric, lifestyle and demographic factors through a mail survey. Unconditional logistic regression analysis was conducted to investigate the association between prostate cancer and early-onset obesity (BMI at age 18) and current obesity. Odds ratios and corresponding 95% confidence intervals were calculated after accounting for significant interaction terms and adjusting for potential confounding variables. This study showed statistically significant association between BMI at age 18 and prostate cancer risk in the multivariate analysis when BMI was evaluated as a continuous variable. There was a 7% decrease in the odds of prostate cancer risk for every 1 kg/m(2) increment in BMI at age 18 (OR=0.93, 95% CI: 0.87, 0.98). Analysis of BMI at age 18 as a categorical variable also showed reduced risk though statistically non-significant. Obese men (OR=0.62, 95% CI: 0.12, 3.08) and overweight men (OR=0.60, 95% CI: 0.35, 1.05) had a non-significant decreased risk of developing prostate cancer compared to normal weight men at age 18. Examination of current BMI showed a non-statistically significant decreased risk of prostate cancer when examined as a continuous variable. However, there was significant interaction between current BMI treated categorically and age. This study concludes that there is decreased prostate cancer risk associated with increasing BMI at age 18. Future large prospective studies are needed to better understand the association between early-onset obesity and risk of prostate cancer and explore the biological factors associated especially in the early ages. This document was created in Microsoft Word 2003.
35
Cong, Chunling. "Statistical Analysis and Modeling of Breast Cancer and Lung Cancer". Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3563.
Testo completoAbstract (sommario):
The objective of the present study is to investigate various problems associate with breast cancer and lung cancer patients. In this study, we compare the effectiveness of breast cancer treatments using decision tree analysis and come to the conclusion that although certain treatment shows overall effectiveness over the others, physicians or doctors should discretionally give different treatment to breast cancer patients based on their characteristics. Reoccurrence time of breast caner patients who receive different treatments are compared in an overall sense, histology type is also taken into consideration. To further understand the relation between relapse time and other variables, statistical models are applied to identify the attribute variables and predict the relapse time. Of equal importance, the transition between different breast cancer stages are analyzed through Markov Chain which not only gives the transition probability between stages for specific treatment but also provide guidance on breast cancer treatment based on stating information.
Sensitivity analysis is conducted on breast cancer doubling time which involves two commonly used assumptions: spherical tumor and exponential growth of tumor and the analysis reveals that variation from those assumptions could cause very different statistical behavior of breast cancer doubling time.
In lung cancer study, we investigate the mortality time of lung cancer patients from several different perspectives: gender, cigarettes per day and duration of smoking. Statistical model is also used to predict the mortality time of lung cancer patients.
36
Kottabi, Zahra. "Statistical Modeling and Analysis of Breast Cancer and Pancreatic Cancer". Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4350.
Testo completoAbstract (sommario):
Abstract
The object of the present study is to apply statistical modeling and estimate the mean of optimism of breast cancer patients as function of attribute variables; delay, education and age for each race of breast cancer patients. Moreover, to investigate the nonlinear association between optimism, education, age and delay with respect to each race and both. Furthermore, to develop differential equations that will characterize the behavior of the pancreatic cancer tumor size as a function of time. Having such differential equations, the mean solution of which once plotted will identify the rate of change of tumor size as a function of age. The structures of the differential equations characterize the growth of pancreatic cancer tumor. Once we have developed the differential equations and their solutions, and the object of the present study is to probabilistically evaluate commonly used methods to perform survival analysis of medical patients to validate the quality of the differential system and discuss its usefulness.
In the last study, a comparison of parametric, semi-parametric and nonparametric analysis of probability survival time models. The first part of the evaluation of survival time by applying the statistical tests will guide us to how precede the actual cancer data and second part, identifying the parametric survival time function for each race and both. Moreover, we will evaluate the Kernel density, the popular Kaplan-Meier (KM) and the Cox Proportional Hazard (Cox PH) models by using actual pancreatic cancer data. As expected, the parametric survival analysis when applicable gives the best results followed by the not commonly used nonparametric Kernel density approach for evaluations actual cancer data.
37
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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38
Hobson, N. J. "Nanoparticle theranostics for applications in cancer diagnostics and cancer therapy". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1546610/.
Testo completoAbstract (sommario):
Traditionally, medicine has been conducted using a diagnostic procedure followed by an appropriate therapy and monitored were possible. On the whole, these steps have happened independently of each other. In recent years however many have started to question this independent approach and have asked whether technologies that seek to combine diagnostics and therapies would be more beneficial at treating diseases. This new medical discipline has been termed theranostics. The aim of this project was to design and synthesise a novel theranostic nanoparticle, using a micelle forming amphiphilic carbohydrate, with the overall hypothesis of determining whether using a nanomedicine that can simultaneously image and treat would improve the effectiveness of a cancer treatment. Super paramagnetic iron oxide nanoparticles (IONPs) have gained considerable attention as an MRI contrast agent due to their unique magnetic properties and relatively inoffensive toxicity profile. Before IONPs may be used in a biological environment they must overcome several challenges, including being stable to aggregation and organ targeting. In this project a modified chitosan amphiphilic polymer was used to successfully formulate IONPs into colloidal stable aqueous dispersions using two different methods which produced blackberry nanoparticles and raspberry nanoparticles. The raspberry nanoparticles were extensively characterised in vitro and in vivo and were found to be highly effective as an MRI imaging probe for the liver and spleen. Following this, they were tested for their cancer imaging properties in an in vivo mouse tumour model. The drug loading capacity of the raspberry nanoparticles was investigated using lomustine, paclitaxel and methotrexate, however no effective drug encapsulation was determined in this project. Overall, a highly effective MRI probe was engineered and characterised, although its future success will be determined by its activity towards a disease target.
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Sarvi, Sana. "Small cell lung cancer and cancer stem cell-like cells". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9542.
Testo completoAbstract (sommario):
Small cell lung cancer (SCLC) is a highly aggressive malignancy with extreme mortality and morbidity. Although initially chemo- and radio-sensitive, almost inevitable recurrence and resistance occurs. SCLC patients often present with metastases, making surgery not feasible. Current therapies, rationally designed on underlying pathogenesis, produce in vitro results, however, these have failed to translate into satisfactory clinical outcomes. Recently, research into cancer stem cells (CSCs) has gained momentum and form an attractive target for novel therapies. Based on this concept, CSCs are the cause of neoplastic tissue development that are inherently resistant to chemotherapy, explaining why conventional therapies can shrink the tumour but are unable to eliminate the tumour completely, leading to eventual recurrence. Here I demonstrate that SCLC H345 and H69 cell lines contain a subset of cells expressing CD133, a known CSC marker. CD133+ SCLC sub-population maintained their stem cell-like phenotype over a prolonged period of culture, differentiated in appropriate conditions and expressed the embryonic stem cell marker Oct-4 indicating their stem-like phenotype. Additionally, these cells displayed augmented clonogenic efficacy, were chemoresistant and tumorigenic in vivo, distinct from the CD133- cells. Thus, the SCLC CD133 expressing cells fulfil most criteria of CSClike definition. The molecular mechanisms associated with CD133+ SCLC chemoresistance and growth is unknown. Up-regulated Akt activity, a known promoter of resistance with survival advantage, was observed in CD133+ SCLC cells. Likewise, these cells demonstrated elevated expression of Bcl-2, an anti-apoptotic protein compared to their negative counterpart explaining CD133+ cell chemoresistance phenotype. Additionally, CD133+ cells revealed greater expression of neuropeptide receptors, gastrin releasing peptide (GRP) and V1A receptors compared to the CD133- cells. Addition of exogenous GRP and arginine vasopressin (AVP) to CD133+ SCLC cells promoted their clonogenic growth in semi-solid medium, illustrating for the first time neuropeptide dependent growth of these cells. A novel peptide (peptide-1) was designed based on the known structure of the substance P analogues that have shown benefit in animal models and in early clinical trials. This compound inhibited the growth of SCLC cells in in vitro with improved potency and stability compared to previous analogues and reduced tumorigenicity in vivo. Interestingly, peptide-1 was more effective in CD133+ cells due to increased expression of neuropeptide receptors on these cells. In conclusion, my results show that SCLC cells retain a sub-population of cells that demonstrate CSC-like phenotype. Preferential activation of Akt and Bcl-2 survival pathways and enhanced expression of neuropeptide receptors contribute to CD133+ SCLC chemoresistance and growth. Therefore, it can be proposed that CD133+ cells are the possible cause of SCLC development, treatment resistance and disease recurrence. Despite being chemoresistant, CD133+ cells demonstrated sensitivity to peptide-1. The identification of such new analogue that demonstrates efficacy towards resistant CD133+ SCLC cells is a very exciting step forward in the identification of a potential new therapy for resistant disease.
40
McMenamin, Úna. "Pharmacological exposures, cancer treatments and disease progression among cancer patients". Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.679267.
Testo completoAbstract (sommario):
The evidence base for the effect of common pharmacological exposures among patients diagnosed with cancer is sparse. Routinely collected health data however, can facilitate the conduct of pharmacoepidemiological research into cancer care and outcomes. This PhD study comprised (i) a systematic review of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use and cancer progression and survival; (ii) a systematic review and meta-analysis of non-steroidal anti-inflammatory drug (NSAID) use and colorectal cancer outcomes; (iii) a nested-case control study of ACEI and ARB use and risk of breast cancer mortality; (iv) a nested-case control study of ACEI and ARB use and risk of prostate cancer mortality and; (v) an overview of cancer treatments received among women, recently diagnosed with breast cancer in Northern Ireland. Individual studies identified within the first systematic review showed inconsistencies with respect to the association between ACEls/ARBs and cancer outcomes and following on from this, findings from two large population-based studies indicated little evidence of a beneficial association between ACEI or ARB use and breast and prostate cancer mortality outcomes, respectively, although a possible protective association was noted for ACEls and risk of prostate cancer mortality. Similarly, there was limited evidence to suggest an association between NSAID use and clinical outcomes from colorectal cancer, based on findings from the second systematic review and meta-analysis. Using data sources from within the Northern Ireland Cancer Registry, a retrospective population-based dataset of breast cancer patients, recently diagnosed in Northern Ireland was constructed. Cancer treatments were deemed appropriate and particular attention was given to adjuvant systemic therapies (including chemotherapy and hormone therapy). This dataset will enable future data linkage with dispensed medication records. Considering the frequency with which ACEls, ARBs, as well as NSAIDs are prescribed, further research into cancer outcomes with respect to these agents is warranted.
41
Roos, Leonie. "Epigenomic studies of twins for cancer and cancer risk factors". Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/epigenomic-studies-of-twins-for-cancer-and-cancer-risk-factors(f500e15c-26e9-48b6-a2ed-e7d30d0f67d9).html.
Testo completoAbstract (sommario):
A complex interaction of environmental factors, stochastic events, and genetic susceptibility can lead to cancer development. The aim of this thesis is to investigate the DNA methylome for cancer, cancer risk, and prediction potential. Studies were performed in peripheral blood to explore systemic changes associated with cancer, and in skin for an in-depth view of total body naevus count, the strongest risk factor for melanoma. Peripheral blood DNA methylomes of 41 cancer-discordant female monozygotic (MZ) twin-pairs were assessed for changes associated with any cancers. The epigenome-wide association study (EWAS) identified one genome-wide significant and several suggestive differential methylated positions (DMPs), three of these showed predictive biomarker potential (near SASH1, COL11A2, and LINC00340). Early breast cancer specific DNA methylation changes were identified in peripheral blood obtained prior to diagnosis. The DNA methylomes were assessed by two genome-wide DNA methylation techniques in a total of 28 breast cancer discordant MZ twin-pairs. Three novel significant breast-cancer differential methylated regions (DMRs) were identified (in MECOM, PCGF3, and near ELN) that were suggestive of predictive biomarker potential. Skin DNA methylomes were investigated in association with the number of naevi across the body in 322 female individuals. Three genome-wide significant DMPs were identified in novel genes METRNL, C15orf48, and ARRDC1. Suggestive results included CTC1 and RAF, which are known genes involved in naevi predisposition and melanoma progression. Approximately half of the 48 suggestive DMRs were correlated with gene expression in cis. Overall, DNA methylation changes related to cancer, pan-cancer and breast cancer specifically, as well as with the melanoma risk factor naevus count were identified. These loci are excellent candidates for further research into their potential as biomarkers or risk factor biological mechanisms in cancer.
42
Wolfman, Jessica Heather Kloss Jacqueline D. "Cancer specific stress and insomnia severity among breast cancer patients /". Philadelphia, Pa. : Drexel University, 2009. http://hdl.handle.net/1860/3024.
Testo completo
43
Wright, Nicola. "Role of cancer stem cells in breast and prostate cancer". Thesis, Sheffield Hallam University, 2016. http://shura.shu.ac.uk/17363/.
Testo completoAbstract (sommario):
Cancer stem cells (CSC) are thought to be responsible for the initiation, propagation and tumour re-occurrence. CSC have been identified in most solid and haematological cancers and account for ~1% of the total cell population. Culturing cancer cell lines in monolayers enriches for the most dominant subpopulation which in most cases does not represent the slow dividing CSC population. We investigated the expression of CSC markers in 2D vs. 3D cell culture with the aim of identifying CSC-like cells via a nanog-reporter cell line and enable the subsequent targeting of these cells with CSC-targeting agents. SUM159 and MCF7 cell lines cultured in 3D cell culture significantly enriched for the CD44+/CD24- breast cancer stem cell phenotype when compared against 2D cell culture (p < 0.05 and 0.001 respectively) and also enriched for expression of CD181 (p < 0.05 and 0.001 respectively). However, this method did not enrich for the prostate CSC with the CD44+/CD133+ phenotype in PC3, DU145 and LNCAP cells. Using reporter cell lines to further identify the CSC population in SUM159 cell line that express GFP in response to Nanog (NRE-GFP), found that these cells were GFP+ve in the absence of Nanog protein. As these reporters were selected based on GFP that was supposedly Nanog driven other mechanistic studies were examined to determine how GFP is expressed in the NRE-GFP and control cell line. It was found that GFP could be induced in apoptosis, CSC enriching medium, hypoxia and by inhibiting the proteasome in the absence of Nanog protein. It was concluded that reporter cell lines that respond to a response element may not identify the CSC population as other factors can induce GFP expression. Compounds related to Withaferin A have been proposed to specifically target CSCs. Prostate and breast cancer cell lines cultured in 2D and 3D were treated with a novel withanolide derivative (LG-02) and Withanilode E to determine if these compounds were more effective at inducing cell cycle arrest and apoptosis using flow cytometry and microscopy. It was determined that LG-02 and WE primary mode of action is cell cycle inhibition and both compounds are more potent cell cycle inhibitors than Withaferin A. G1 phase accumulation was observed in the SUM159, PC3 and LNCAP cell lines and G2/M phase accumulation in the DU145 cell line. Cell cycle arrest was inconclusive in the MCF7 cell line. An apoptotic morphology was only significantly induced at higher concentrations in MCF7, PC3, DU145 and LNCAP. Withanolide derivatives also target the androgen response pathway, demonstrated by a decrease in PSA and androgen receptor in prostate cancer cell lines. LG-02 slowed growth of breast cancer cell lines cultured in 3D and inhibited spheroid formation of prostate cancer cell lines, however the androgen-dependent cell line LNCAP was consistently able to form 3D colonies, most likely via pAkt activation. We conclude that 3D cell culture does enrich for the CSC population in breast cancer cell lines but using a reporter cell line expressing GFP under the control of a NRE is not a suitable model for identifying the CSC population for subsequent drug treatment. In addition, Withanolide derivatives have potential anti-tumour activity and may represent a novel class of anti-androgenic agents.
44
Clinton, Christine. "Socioeconomic Status and Cancer Risks in Employer-Insured Cancer Survivors". ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5616.
Testo completoAbstract (sommario):
Chronic illnesses such as cancer continue to be among the costliest for employers who provide health insurance to their employees. Despite efforts to incorporate health improvement programs in the workplace, there are concerns about the effectiveness of these programs that do not always deliver a positive return on investment. Little is known about the specific socioeconomic status of employees for whom these workplace health improvement programs are designed for. Guided by the social-ecological model, this study sought to understand the relationship between cancer health risks about socioeconomic factors among cancer survivors in the employer-insured population. Data were extracted from the 2013 Behavioral Risk Factor Surveillance System for employer-insured individuals who identified as having been diagnosed with cancer at some point in their life (N = 7,007). A multivariate linear regression analysis was used to assess the effect of household income, level of education, race/ethnicity of respondents on cancer health risks based on the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention (ACS). The analysis of variance indicated that the overall model was significant (P < .05). College graduates had the highest level of compliance with requirement for cancer prevention; participants' adherence to the guidelines varied depending on their household income. This study may contribute to positive social change as it suggests that socioeconomic characteristics of employer-insured individuals, including health history, need to be taken into consideration in the development and implementation of worksite health improvement programs.
45
Kishi, Masae. "Strategies of Cancer Immunotherapy : Model of Triple Negative Breast Cancer". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS070.
Testo completoAbstract (sommario):
Les cellules souches cancéreuses (CSC) sont à l’origine de la progression tumorale, des métastases et rechutes tardives. Elles ont été identifiées dans de nombreux cancers, comme le cancer du sein triple négatif (TNBC) et cancers de grade III-IV. Elles sont résistantes aux chimiothérapies et radiothérapie et résident dans une niche immuno-répressive. Cette étude vise à évaluer une stratégie d’immunothérapie qui cible sélectivement les CSC dans le modèle murin 4T1-GFP-Luc mimant le TNBC. Le phénotype/ génotype des mamosphères a été initialement caractérisé. Basée sur l’analyse génomique des CSC, nous avons développé une immunothérapie active associée à des agents immuno-modulateurs. Nous avons mesuré la taille des tumeurs et suivi l’apparition des métastases par bioluminescence. Une étude immunologique et analyse génomique de la tumeur a été réalisée. La combinaison thérapeutique provoque le recrutement dans la tumeur de lymphocytes T (CD4 +, CD8 +) et lymphocytes B par augmentation de CXCL13, une réduction des lymphocytes T reg et cellules myéloïdes suppressives. Cette induction de réponse immunitaire provoque la diminution de la taille de la tumeur et des métastases. Cette nouvelle immunothérapie active de type vaccinale pourra être utilisée en association avec les traitements actuels pour des mesures prophylactiques et curatives dans une grande variété de cancersCancer stem cells (CSCs) are responsible for tumor progression, metastases, and late relapses. They have been identified in many cancers, such as triple negative breast cancer (TNBC) and grade III to IV cancers. They are resistant to chemotherapy and radiotherapy and reside in an immuno-repressive niche.This study aims to evaluate a immunotherapy strategy that selectively targets CSCs in the mouse model 4T1-GFP-Luc mimicking TNBC. The phenotype / genotype of mammosphere was initially characterized. Based on genomic analysis of CSC, we have developed an active immunotherapy associated with immunomodulatory agents. We measured the size of tumors and monitored the appearance of metastases by bioluminescence. We performed an immunological study and genomic tumor analysis. The therapeutic combination causes the recruitment of CD4 + and CD8 + T lymphocytes and B lymphocytes with increased CXCL13, the reduction of T reg cells and suppressive myeloid cells in the tumor. This induction of intra-tumor immune response leads to a decrease in tumor size and metastases.This new active immunotherapy can be used in combination with current treatments for prophylactic and curative measures in a wide variety of cancers
46
Kishi, Masae. "Strategies of Cancer Immunotherapy : Model of Triple Negative Breast Cancer". Electronic Thesis or Diss., Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS070.
Testo completoAbstract (sommario):
Les cellules souches cancéreuses (CSC) sont à l’origine de la progression tumorale, des métastases et rechutes tardives. Elles ont été identifiées dans de nombreux cancers, comme le cancer du sein triple négatif (TNBC) et cancers de grade III-IV. Elles sont résistantes aux chimiothérapies et radiothérapie et résident dans une niche immuno-répressive. Cette étude vise à évaluer une stratégie d’immunothérapie qui cible sélectivement les CSC dans le modèle murin 4T1-GFP-Luc mimant le TNBC. Le phénotype/ génotype des mamosphères a été initialement caractérisé. Basée sur l’analyse génomique des CSC, nous avons développé une immunothérapie active associée à des agents immuno-modulateurs. Nous avons mesuré la taille des tumeurs et suivi l’apparition des métastases par bioluminescence. Une étude immunologique et analyse génomique de la tumeur a été réalisée. La combinaison thérapeutique provoque le recrutement dans la tumeur de lymphocytes T (CD4 +, CD8 +) et lymphocytes B par augmentation de CXCL13, une réduction des lymphocytes T reg et cellules myéloïdes suppressives. Cette induction de réponse immunitaire provoque la diminution de la taille de la tumeur et des métastases. Cette nouvelle immunothérapie active de type vaccinale pourra être utilisée en association avec les traitements actuels pour des mesures prophylactiques et curatives dans une grande variété de cancersCancer stem cells (CSCs) are responsible for tumor progression, metastases, and late relapses. They have been identified in many cancers, such as triple negative breast cancer (TNBC) and grade III to IV cancers. They are resistant to chemotherapy and radiotherapy and reside in an immuno-repressive niche.This study aims to evaluate a immunotherapy strategy that selectively targets CSCs in the mouse model 4T1-GFP-Luc mimicking TNBC. The phenotype / genotype of mammosphere was initially characterized. Based on genomic analysis of CSC, we have developed an active immunotherapy associated with immunomodulatory agents. We measured the size of tumors and monitored the appearance of metastases by bioluminescence. We performed an immunological study and genomic tumor analysis. The therapeutic combination causes the recruitment of CD4 + and CD8 + T lymphocytes and B lymphocytes with increased CXCL13, the reduction of T reg cells and suppressive myeloid cells in the tumor. This induction of intra-tumor immune response leads to a decrease in tumor size and metastases.This new active immunotherapy can be used in combination with current treatments for prophylactic and curative measures in a wide variety of cancers
47
Irobi, Edward Okezie. "Time to Diagnosis of Second Primary Cancers among Patients with Breast Cancer". ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2661.
Testo completoAbstract (sommario):
Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan-Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, 95% CI [1.03 - 2.11], White = 1.511, 95% CI [1.18 - 1.94], and American Indian/Hawaiian = 1.424, 95% CI [1.12 -1.81] showing positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.
48
Niksic, Maja. "Public cancer awareness and cancer survival in England : recognition of cancer symptoms and perception of barriers to seeking medical help in relation to breast, lung and bowel cancer survival in England". Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/public-cancer-awareness-and-cancer-survival-in-england(d8715922-6635-4840-8c4f-66c26adbf0c2).html.
Testo completo
49
Tong, Ka-keung. "Cancer Treatment Centre". Click to view the E-thesis via HKUTO, 1996. http://sunzi.lib.hku.hk/hkuto/record/B31983066.
Testo completoAbstract (sommario):
Thesis (M.Arch.)--University of Hong Kong, 1996.Includes special report study entitled : Hospital planning study for the cancer treatment centre. Includes bibliographical references. Also available in print.
50
Knudsen, Anne Kari. "Cancer pain classification". Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for kreftforskning og molekylær medisin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-16631.
Testo completoAbstract (sommario):
Klassifikasjon av kreftsmerte Kreftsmerte – hva skal et fremtidig klassifikasjonssystem inneholde? Smerte er et subjektivt, sammensatt og plagsomt symptom som forekommer hyppig hos kreftpasienter. Til tross for eksisterende retningslinjer, er det mange kreftpasienter som ikke får god smertebehandling, særlig ved langkommet sykdom. En av mange årsaker til dette, er mangelen på et allment akseptert klassifiseringssystem for kreftsmerte – et verktøy for å stille en korrekt diagnose. På bakgrunn av ovennevnte forhold ble den internasjonale EU-finansierte forskningsgruppen ‘European Palliative Care Research Collaborative’ (EPCRC) dannet. En av gruppens hovedmålsettinger var å utvikle klassifikasjonssystem for tre vanlige symptomer hos kreftpasienter med langtkommet sykdom: smerte, depresjon og ufrivillig vekttap. Arbeidene i denne avhandlingen har vært utført i nær tilknytning til EPCRC. Det overordnete målet med avhandlingen er å bidra i utviklingsprosessen av et internasjonalt klassifikasjonssystem for smerte hos kreftpasienter blant annet ved å finne frem til noen faktorer som er avgjørende for å kunne beskrive en smertetilstand og derved å kunne stille en korrekt smertediagnose. Hovedfunnene i avhandlingen er: Det foreligger flere systemer for klassifisering av smerte hos kreftpasienter, men ingen av disse er i utstrakt bruk, verken i forskning eller klinisk praksis. Smertens intensitet og patofysiologi, forekomst av gjennombruddssmerte, psykisk stress og respons på behandling inngår i to eller flere av de seks formelle systemene som ble funnet ved systematisk litteraturgjennomgang. Pasienter bekreftet i intervju at faktorer påvist å være viktige for kreftsmerte i tidligere studier, også var relevante for deres smerteopplevelse. De vektla fysiske og psykiske aspekter ved det å ha smerte, og søvn ble ansett som en viktig faktor. I en europeisk studie hvor mer enn 2000 kreftpasienter som brukte sterke smertestillende (opioider) deltok, ble følgende faktorer funnet å ha betydning for grad av smerteintensitet og/eller smertelindring: gjennombruddssmerte, smertens lokalisasjon, opioiddose, bruk av svake smertestillende, søvn, psykisk stress, smertens patofysiologi, misbruk av alkohol/narkotika, kreftdiagnose og lokalisasjon av spredning av kreftsykdommen. I en italiensk studie hvor 1800 kreftpasienter deltok, ble de fem førstnevntes relevans bekreftet. Videre ble det i den samme studien påvist at smerteintensitet og opplevd smertelindring målt ved studiens oppstart samt forekomst av gjennombruddssmerte, smertens lokalisasjon, alder og kreftdiagnose var faktorer som kunne predikere smerte etter to uker. Minst tre hovedutfordringer må løses for å komme nærmere et internasjonalt klassifikasjonssystem for kreftsmerte: å velge de mest relevante faktorene for inklusjon i systemet, inkludert å velge et tilstrekkelig antall faktorer, å oppnå enighet om hvilke endepunkt som skal brukes og til slutt å innføre det fremtidige klassifikasjonssystemet i klinisk praksis.Cancer pain classification – what should be the content of a future system? Pain is a subjective, complex and burdensome symptom which is very common in cancer patients. Despite existing treatment guidelines, several cancer patients still do not receive optimal pain treatment, in particular patients with advanced disease. The lack of a common classification system for cancer pain – a diagnostic tool – has been identified as one of several causes for this undertreatment. Motivated by these considerations, the international EU-funded ‘European Palliative Care Research Collaborative’ (EPCRC) was established. One of the main aims was to develop a classification system for three common symptoms in cancer patients with advanced disease: pain, depression, and cancer related weight loss. The papers included in this thesis have been performed in close collaboration with the EPCRC. The overall aim of the thesis is to contribute in the development process of an international classification system for pain in cancer patients by for example to identify factors that are important for describing pain and thus improve diagnostics and treatment of cancer pain. The main results in this thesis are: There are several systems for pain classification in cancer patients, but none of these are widely used in research or in clinical practice. Pain intensity and pathophysiology, the presence of breakthrough pain, psychological distress, and response to treatment are included in two or more of the six formal systems that were identified by systematically reviewing existing literature. Patients confirmed in interviews that the factors identified to be important for cancer pain in previous studies, were relevant also for their experience of pain. They emphasised physical and psychological aspects of being in pain, and sleep was considered important. In an European study where more than 2000 cancer patients using strong pain medication (opioids) participated, the following factors were identified to be of importance for the degree of pain intensity and pain relief: breakthrough pain, localisation of pain, opioid dose, use of weak pain medication, sleep, psychological distress, pathophysiology of pain, substance abuse, cancer diagnosis, and localisation of metastases. In an Italian study where 1800 cancer patients participated, the relevance of the five first factors listed above was confirmed. Furthermore, results from the same study showed that pain intensity and pain relief measured at study start as well as the presence of breakthrough pain, localisation of pain, age, and cancer diagnosis were factors that could predict pain after two weeks. At least three major challenges for the further development a future international classification system for cancer pain: to choose the most relevant factors (and how many) to include in the system, to achieve agreement on what outcomes to use, and finally to start using the classification system in clinical practice