Dissertations / Theses: 'Cancer Clusters'

1

Rattican, Debra. "Symptom Clusters in Lung Cancer Patients." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/352.

Full text

Abstract:

SYMPTOM CLUSTERS IN LUNG CANCER PATIENTS By Debra Rattican, PhD, RN A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Director: Debra E. Lyon, PhD. Professor and Chair Family and Community Health Nursing The purpose of the study was to examine selected relationships among symptoms common to individuals with lung cancer. The specific aims were: 1) To examine the relationship between the symptoms of dyspnea and anxiety in patients with lung cancer. 2) To examine the relationships among the symptoms of dyspnea, anxiety, and symptom cluster components (depressive symptoms, fatigue, pain) in patients with lung cancer. 3) To examine the correlation between functional ability and quality of life in patients with lung cancer. 4) To explore the relationships among the symptoms of dyspnea, anxiety, and symptom cluster components (depressive symptoms, fatigue, pain) in patients with lung cancer and patients’ functional ability. 5) To explore the relationships among the symptoms of dyspnea, anxiety, and symptom cluster components (depressive symptoms, fatigue, pain) in patients with lung cancer and patients’ quality of life. Data were gathered through online survey and analyzed using descriptive, correlation, principal component analysis, exploratory factor analysis, and forward stepwise regression techniques. A strong positive correlation was found between dyspnea and anxiety (both anxiety in general and anxiety at the time the survey was completed. While results of this study cannot provide conclusive evidence of the existence of a symptom cluster composed of depressive symptoms, fatigue, and pain, the results are consistent with other studies in this area. Significant positive correlations among these three symptoms indicate that this is a possible symptom cluster experienced by lung cancer patients in general. This study provides preliminary data on how these symptoms are related and how they affect functional ability, or the ability to perform routine activities of daily living (ADLS) and instrumental activities of daily living (IADLS), and quality of life in patients with lung cancer. Further study is needed on to better understand the symptom experience of these individuals in order to develop robust interventions targeting effective symptom management.

APA, Harvard, Vancouver, ISO, and other styles

2

Chau, Hau-yan, and 周厚仁. "Symptom clusters among Chinese women with breast cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48422563.

Full text

Abstract:

Background: breast cancer patients were found to experience multiple concurrent symptoms. These concurrent symptoms (termed symptom cluster) could have synergistic effects on patient functional status and quality of life. Understanding symptom cluster provided us new insight in symptom assessment and symptom management. Previous studies on symptom cluster among breast cancer patients focused on Caucasian. The current study attempt to identify symptom cluster and the factors associated with it among Chinese breast cancer patients. Methods: this study was a secondary analysis on a sample of 348 breast cancer patients. Data on symptom distress (assessed by Memorial symptom Assessment scale Short Form) was retrieved. Symptom clusters were identified through factor analysis using principal components method and Varimax rotation. Demographics and medical characteristics were proposed to be associated with symptom cluster. Uni-variate analysis and linear regression performed on these variables. Results: four symptom clusters (namely gastrointestinal cluster, general malaise cluster, self image cluster, and cutaneous cluster) were identified. Recurrence of breast cancer and chemotherapy were associated with either gastrointestinal cluster or general malaise cluster. Age, cancer status and occupation were associated with self image cluster while no variable was associated with cutaneous cluster. Conclusion: The current study provided empirical evidence that Chinese breast cancer patients experienced similar symptom clusters as Caucasian. Future study could be done to verify these four symptom clusters and identify underlying mechanism. Recommendations: health care providers could pay more attention to those suffer from breast cancer recurrence or currently receiving chemotherapy. These patients tend to experience gastrointestinal cluster and general malaise cluster. Clinical setting and evaluation tools could be adjusted to fit these high risk groups.
published_or_final_version
Public Health
Master
Master of Public Health

APA, Harvard, Vancouver, ISO, and other styles

3

Maguire, Roma. "Where is the person in symptom cluster research? : the experience of symptom clusters in patients with advanced lung cancer." Thesis, University of Stirling, 2011. http://hdl.handle.net/1893/3423.

Full text

Abstract:

Where is the Person in Symptom Cluster Research? The Experience of Symptom Clusters in Patients with Advanced Lung Cancer This thesis describes a three-year qualitative study which aimed to explore the experience of symptom clusters in patients with advanced lung cancer. The study employed a patient-focused approach utilising Interpretative Phenomenological Analysis (IPA) (Smith et al. 2009a). This methodology (IPA), informed by a contextual constructionist stance, was selected to explore the experience of symptom clusters, for its focus on the lived experience, the context and meanings which surround such experiences and its idiographic approach. Ten patients (a sample size which is the upper limit of the number of participants advocated for studies employing IPA (Smith et al. 2009b;Reid et al. 2005;Smith and Osborn 2004)) with advanced lung cancer took part in the study and data were collected using unstructured, in-depth interviews at two time points: on recruitment and three to five weeks later. Data were analysed using Interpretative Phenomenological Analysis, within the framework advocated by Smith and Osborn (2003). The study generated interesting and significant findings. The experience of symptom clusters in patients with advanced lung cancer was characterised by two super-ordinate themes: ‘The lived experience of symptom clusters and the role of context and meaning’ and ‘Symptom clusters and loss of sense of self’. The super-ordinate theme of ‘The lived experience of symptom clusters and the role of context and meaning’ in the first instance, illustrates that the participants in this study were experiencing symptom clusters and providing detail on the components, nature and patterning of the symptom clusters reported, particularly the way that one or two salient symptoms were commonly highlighted from all the other symptoms experienced. This super-ordinate theme also demonstrates the core role that context and meaning play in the lived experience of symptom clusters, with many of the participants in this study framing their experiences of symptom clusters within a fear of death, stigma and loss of sense of self. The second super-ordinate theme informing this thesis is ‘Symptom clusters and loss of sense of self’. This super-ordinate theme illustrates the impact of symptom clusters on the participants’ lives, and how this, in turn, impacted on their sense of self in a number of different ways. For some, their sense of self was compromised by the concurrent symptoms that they were experiencing, as they prevented them from undertaking roles and activities that they were accustomed to in the past. This super-ordinate theme also highlights the role of the body relative to the self, and describes how the participants’ sense of self was transiently lost during periods when they experienced symptom clusters of high severity. The findings presented also demonstrate the knock-on effect of loss of sense of self experienced, with the participants feeling like they were a burden due to their incapacitation, and at times hiding the multiple symptoms that they were experiencing, in a bid to protect their loved ones from their illness. In light of the loss of sense of self experienced, this super-ordinate theme also demonstrates how the participants employed various strategies in a bid to try and maintain a coherent and valued sense of self. The findings presented illustrate how the use of IPA facilitated the collection of data that provided an in-depth understanding of the complexity of the experience of symptom clusters in patients with advanced lung cancer, adding a unique contribution to this body of knowledge. The results of this study highlight the limitations of definitions that currently underpin the study of symptom clusters in patients with cancer and the current empirical base to date, particularly the way that they do not acknowledge the core role that context and meaning play in the lived experience of this phenomenon. This lack of recognition of these core elements of the patient experience of symptom clusters poses the risk of this body of research producing data that have limited relevance to the patient and therefore clinical practice. It is therefore proposed that the study of symptom clusters in patients with cancer needs to move away from the reductionist approach which currently dominates and to broaden its scope, to one that acknowledges the complexity of the experience of symptom clusters, the core role that context and meaning play in such experiences, and contributions that patient experience can make in advancing this important and emerging body of research.

APA, Harvard, Vancouver, ISO, and other styles

4

Kim, Jung-Eun Esther. "Multiple symptoms and symptom clusters in patients with cancer." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3324589.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Stults, Dawn Michelle. "Human ribosomal RNA gene clusters are recombinational hotspots in cancer." Lexington, Ky. : [University of Kentucky Libraries], 2009. http://hdl.handle.net/10225/1122.

Full text

Abstract:

Thesis (M.S.)--University of Kentucky, 2009.
Title from document title page (viewed on May 6, 2009). Document formatted into pages; contains: v, 27 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 25-26).

APA, Harvard, Vancouver, ISO, and other styles

6

Morrison, Eleshia JP. "Examining the Presence of Symptom Clusters in Patients with Advanced Cancer." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1259769198.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Dong, Skye Tian. "Symptom Clusters in Patients with Advanced Cancer: A mixed methods investigation." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/14987.

Full text

Abstract:

Patients with advanced cancer typically experience symptom clusters or multiple concurrent symptoms, which have a detrimental impact on patient outcomes. Research in symptom management has predominantly focused on investigating single symptoms in isolation. Although the literature on symptom clusters is growing, the composition of symptom clusters differs depending on the various clinical variables and the method of their assessment and statistical analysis. Effective management of multiple concurrent symptoms in advanced cancer patients remains a clinical challenge across healthcare settings. Minimal attention has been given to gaining a broad and in-depth understanding about the experiences, perspectives, and attitudes of patients with multiple symptoms and clinicians treating symptom clusters. This thesis describes a systematic review of symptom clusters in advanced cancer (Study 1) and three empirical studies that aimed to explore: the composition of symptom clusters in advanced cancer and their influence on patient outcomes (Study 2); patients’ experiences of living with multiple symptoms (Study 3); and multidisciplinary clinicians’ attitudes and strategies towards managing symptom clusters in advanced cancer (Study 4). The overarching purpose of this thesis was to qualitatively investigate the experience of multiple concurrent symptoms from patients’ and clinicians’ perspectives, whilst simutaneously examine how this converges with and diverges from a quantitative investigation of symptom clusters in advanced cancer patients. This mixed methods study design allows for a complete understanding of the impact of symptom clusters on both qualitative and quantitative accounts of quality of life and functioning. Chapter 3 – Systematic review Method: In Study 1, to understand what is known about the composition, stability, consistency, and impact of symptom clusters in advanced cancer patients, the relevant literature was systematically reviewed. Medline, CINAHL, Embase, Web of Science, and PsychINFO were searched to identify studies investigating variants of symptom clusters, cancer, and palliative care. After screening 977 potentially eligible articles, 33 articles were systematically reviewed and assessed for quality. Results: Four common groupings of symptom clusters were found: anxiety-depression, nausea-vomiting, nausea-appetite loss, and fatigue-dyspnea-drowsiness-pain. Symptom clusters in most cases were not stable longitudinally and the various statistical methods used tended to reveal different symptom clusters. The predictors and outcomes of symptom clusters and measurement tools used were also inconsistent across studies. Future studies need to explore the influence of statistical methods on symptom cluster composition, which symptom clusters predict patient outcomes, and patients’ subjective experience of symptom clusters. Chapter 5 – Quantitative study Method: Study 2 examined the extent to which different statistical methodologies differ in the symptom cluster composition solutions they produce across five primary cancer sites, and determine which symptom clusters predict patient outcomes. One hundred and fifty variations of principal component analysis, exploratory factor analysis, and hierarchical cluster analysis were used on an existing data set (N = 1562) of advanced cancer patients who completed the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30. Results: Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. Chapter 6 – Qualitative study on patients with advanced cancer Method: Study 3 examined advanced cancer patients’ experiences of multiple concurrent symptoms using thematic analysis and an adapted grounded theory approach to data collection and analysis. Semi-structured interviews (N = 58) were conducted with 23 inpatients and 35 outpatients recruited purposively from two palliative care centres and two hospital-based oncology departments in Sydney, Australia. Participants were sampled to include a range of cancers and phases in advanced cancer. Results: Six major themes were identified: imminence of death and deterioration; overwhelming loss of control; impinging on autonomy and identity; psychological adaptation; burden of self-management responsibility; and valuing security and empowerment. Multiple symptoms have a profound impact on patients’ autonomy, function, and psychological state and patients transitioning from oncology to palliative care settings were more vulnerable to self-management burden. Chapter 7 – Qualitative study on clinicians managing symptom clusters in advanced cancer Method: Study 4 examined clinicians’ experiences, strategies, and attitudes towards the management of multiple concurrent symptoms in advanced cancer patients using thematic analysis and adapted grounded theory. In-depth semi-structured interviews (N = 48) were conducted with 10 palliative care physicians, 6 oncologists, 6 general practitioners, 12 nurses, and 14 allied health providers, purposively recruited from two acute hospitals, two palliative care centres, and four community general practices in Sydney, Australia. Results: Six themes were identified: uncertainty in decision making; attunement to patient and family; deciphering cause to guide intervention; balancing complexities in medical management; fostering hope and empowerment; and depending on multidisciplinary expertise. Managing symptom clusters, is both an art and a science currently fraught with uncertainty in decision making. Increased scientific evidence for treating symptom clusters and effective collaboration across settings is vital. Conclusions Integration of symptom cluster research into clinical practice is in its infancy. A psychosocial pathway in the management of symptom clusters was proposed as possibly improving quality of life, and biological mechanisms underpinning symptom clusters require further investigation. Multiple symptom management and integrated care is needed to empower advanced cancer patients and reduce their struggles with self-management burden, particularly as they transition between oncologic and palliative care. Strengthening multidisciplinary collaboration, continuity of care, more pragmatic planning of clinical trials to address the multiple symptom experience, and training in symptom cluster assessment and management is crucial. Future research needs to target translating the body of symptom cluster literature into clinically relevant guidelines and interventions across settings, to support a move towards advancing healthcare and research for symptom management in advanced cancer patients.

APA, Harvard, Vancouver, ISO, and other styles

8

Skerman, Helen Mary. "Alternative analytical methods for the identification of cancer-related symptom clusters." Thesis, Queensland University of Technology, 2010. https://eprints.qut.edu.au/34503/1/Helen_Skerman_Thesis.pdf.

Full text

Abstract:

Advances in symptom management strategies through a better understanding of cancer symptom clusters depend on the identification of symptom clusters that are valid and reliable. The purpose of this exploratory research was to investigate alternative analytical approaches to identify symptom clusters for patients with cancer, using readily accessible statistical methods, and to justify which methods of identification may be appropriate for this context. Three studies were undertaken: (1) a systematic review of the literature, to identify analytical methods commonly used for symptom cluster identification for cancer patients; (2) a secondary data analysis to identify symptom clusters and compare alternative methods, as a guide to best practice approaches in cross-sectional studies; and (3) a secondary data analysis to investigate the stability of symptom clusters over time. The systematic literature review identified, in 10 years prior to March 2007, 13 cross-sectional studies implementing multivariate methods to identify cancer related symptom clusters. The methods commonly used to group symptoms were exploratory factor analysis, hierarchical cluster analysis and principal components analysis. Common factor analysis methods were recommended as the best practice cross-sectional methods for cancer symptom cluster identification. A comparison of alternative common factor analysis methods was conducted, in a secondary analysis of a sample of 219 ambulatory cancer patients with mixed diagnoses, assessed within one month of commencing chemotherapy treatment. Principal axis factoring, unweighted least squares and image factor analysis identified five consistent symptom clusters, based on patient self-reported distress ratings of 42 physical symptoms. Extraction of an additional cluster was necessary when using alpha factor analysis to determine clinically relevant symptom clusters. The recommended approaches for symptom cluster identification using nonmultivariate normal data were: principal axis factoring or unweighted least squares for factor extraction, followed by oblique rotation; and use of the scree plot and Minimum Average Partial procedure to determine the number of factors. In contrast to other studies which typically interpret pattern coefficients alone, in these studies symptom clusters were determined on the basis of structure coefficients. This approach was adopted for the stability of the results as structure coefficients are correlations between factors and symptoms unaffected by the correlations between factors. Symptoms could be associated with multiple clusters as a foundation for investigating potential interventions. The stability of these five symptom clusters was investigated in separate common factor analyses, 6 and 12 months after chemotherapy commenced. Five qualitatively consistent symptom clusters were identified over time (Musculoskeletal-discomforts/lethargy, Oral-discomforts, Gastrointestinaldiscomforts, Vasomotor-symptoms, Gastrointestinal-toxicities), but at 12 months two additional clusters were determined (Lethargy and Gastrointestinal/digestive symptoms). Future studies should include physical, psychological, and cognitive symptoms. Further investigation of the identified symptom clusters is required for validation, to examine causality, and potentially to suggest interventions for symptom management. Future studies should use longitudinal analyses to investigate change in symptom clusters, the influence of patient related factors, and the impact on outcomes (e.g., daily functioning) over time.

APA, Harvard, Vancouver, ISO, and other styles

9

Crane, Tracy E., and Tracy E. Crane. "Symptom Clusters and Trajectories of Depression and Anxiety in Latina Breast Cancer Survivors." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/621858.

Full text

Abstract:

Background: Latinas experience a greater number of symptoms and are at an elevated risk for depression and anxiety following a diagnosis of breast cancer compared to Non-Hispanic Whites and African Americans. Cancer-related symptom clusters are frequently reported in women with breast cancer and research suggests these women follow distinct trajectories for depression and anxiety. However, little is known about the trajectories of anxiety and depression or cancer-related symptom clusters in Latinas with breast cancer. Methods: 296 Latinas previously recruited and diagnosed with breast cancer comprised this sample. Questionnaires for depression (the Center for Epidemiological Studies-Depression) and Anxiety (Speilberger State-Trait Inventory and PROMIS Anxiety) were administered at baseline, 2 and 4 months post enrollment. To identify classes of Latina breast cancer survivors based on patterns of symptom occurrence, symptoms latent class analysis was used to describe symptom clusters. Group-based growth mixture modeling was utilized to identify classes of women who followed distinct trajectories of depression and anxiety. Results: On average women reported 4.2±3 symptoms with an overall symptom distress score of 6.4±2.5 (out of a scale of 10). Three symptom classes were identified: Weary and Sleepy (class 1), Weary (class 2) and Weary, Sleepy and Hurting (class 3). Women were most likely to cluster in class 1, followed by class 2 and 3 with fatigue (labeled weary) being the most prevalent symptom for all three classes. Three trajectories emerged for both depression and anxiety. For depression, the majority of women (79.6%) fell in the high then reducing trajectory for depression followed by the low and remaining low (17%) and the high and increasing (worsening) trajectories of depression (3%). For anxiety the majority (78% of women) followed the moderate to increasing (worsening) trajectory of anxiety followed by 14% in the moderate to declining (improving) and 8% in the low to slightly increasing (worsening) trajectories for anxiety. Conclusion: This study suggests Latina breast cancer survivors experience burdensome cancer-related symptom clusters and distinct trajectories for depression and anxiety. Further research is needed in minority women with breast cancer to adequately understand and treat cancer-related symptom clusters as well as depression and anxiety.

APA, Harvard, Vancouver, ISO, and other styles

10

Stults, Dawn Michelle. "STRUCTURAL INSTABILITY OF HUMAN RIBOSOMAL RNA GENE CLUSTERS." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/68.

Full text

Abstract:

The human ribosomal RNA genes are critically important for cell metabolism and viability. They code for the catalytic RNAs which, encased in a housing of more than 80 ribosomal proteins, link together amino acids by peptide bonds to generate all cellular proteins. Because the RNAs are not repeatedly translated, as is the case with messenger RNAs, multiple copies are required. The genes which code for the human ribosomal RNAs (rRNAs) are arranged as clusters of tandemly repeated sequences. Three of four catalytic RNAs are spliced from a single transcript. The genes are located on the short arms of the five acrocentric chromosomes (13, 14, 15, 21, and 22). The genes for the fourth rRNA are on chromosome 1q42, also arranged as a cluster of tandem repeats. The repeats are extremely similar in sequence, which makes them ideal for misalignment, non‐allelic homologous recombination (NAHR), and genomic destabilization during meiosis , replication, and damage repair. In this dissertation, I have used pulse‐field gel electrophoresis and in‐blot Southern hybridization to explore the physical structure of the human rRNA genes and determine their stability and heritability in normal, healthy individuals. I have also compared their structure in solid tumors compared to normal, healthy tissue from the same patient to determine whether dysregulated homologous recombination is an important means of genomic destabilization in cancer progression. Finally, I used the NCI‐60 panel of human cancer cell lines to compare the results from the pulsed‐field analysis, now called the gene cluster instability (GCI) assay, to two other indicators of homologous‐recombination-mediated genomic instability: sister chromatid exchange, and 5‐hydroxymethyl‐2’deoxyuridine sensitivity.

APA, Harvard, Vancouver, ISO, and other styles

11

Le, Boiteux Elisa. "Altération du contrôle de H3K27me3 et dérégulation transcriptionnnelle dans les gliomes : études des clusters HOX." Thesis, Université Clermont Auvergne‎ (2017-2020), 2019. http://www.theses.fr/2019CLFAS027.

Full text

Abstract:

Il est largement documenté que les patrons épigénétiques sont altérés dans les cancers. Pour autant, l’étendue et la nature précise de ces altérations, tout comme leur impact sur l’expression des gènes, restent encore peu appréciés. Mon projet de thèse est bâti sur ce constat, et s’inscrit en particulier dans la recherche des causes et conséquences des altérations épigénétiques dans les gliomes. Ces tumeurs du système nerveux central représentent en effet un excellent modèle, car elles présentent des défauts de méthylation de l’ADN permettant de discriminer deux populations de tumeurs avec des caractéristiques cliniques différentes. Notre stratégie, basée sur des analyses moléculaires exhaustives, s’est appuyée sur une cohorte de 70 échantillons tumoraux, classés sur la base de leur statut IDH, et de six lignées de cellules souches de glioblastomes (CSG).Ces travaux ont tout d’abord permis de relativiser la contribution de la méthylation de l’ADN dans les dérégulations transcriptionnelles observées dans les gliomes. Il apparait en effet que ce sont plutôt les altérations au niveau de la chromatine bivalente, et plus spécifiquement de la marque H3K27me3, qui sont la cause principale de ces dérégulations transcriptionnelles. Spécifiquement, nos données supportent un modèle selon lequel l’altération dans le contrôle de la marque H3K27me3, et plus spécifiquement dans les interactions entre le complexe PRC2 et la machinerie de transcription spécifique au cerveau, est la cause principale des altérations transcriptionnelles dans les gliomes.Cette étude révèle également que les gènes à homéodomaine, et en particulier les gènes HOX, constituent une catégorie à part dans les gliomes les plus agressifs (IDHwt). Leur signature moléculaire, associant gain d’expression et gain de méthylation de l’ADN, est en effet atypique. Nos données révèlent que cette altération est généralisée aux quatre clusters HOX, et que la réactivation de ces gènes est liée à la perte drastique et spécifique de la marque H3K27me3 sur ces régions. Cette étude conduit également à proposer un modèle original selon lequel l’hypométhylation globale de l’ADN est un élément déclencheur de l’expression ectopique détectée au niveau de nombreux gènes, et dont l’altération des gènes HOX aurait, via un effet domino, un rôle central. L’observation de l’altération de la marque H3K27me3 dans les gliomes, et en particulier aux clusters HOX, nous a également amené à nous interroger sur le rôle des ARN non codants dans ces mécanismes. En ce sens, un transcrit non codant encore peu caractérisé, nommé HOXA-AS2 (situé en antisens au niveau du cluster HOXA), a été identifié. Ce transcrit est significativement et spécifiquement surexprimé dans les gliomes IDHwt. Des approches de sous-expression dans des lignées bien caractérisées de CSG suggèrent un rôle central de HOXA-AS2 dans la biologie de ces cellules. Il contribuerait ainsi au caractère pathologique des CSG en inhibant les voies de l’inflammation et en favorisant la capacité des cellules à proliférer.Dans son ensemble, ce travail revisite le lien entre altérations épigénétiques et défauts d’expression dans les cancers et met en évidence qu’une altération dans le contrôle de la marque H3K27me3 est la principale cause des défauts d’expression des gènes
Epigenetic alterations are a well-known signature of cancer cells. However, the causes of these defects, as well as their consequence on gene expression, remain elusive. My thesis project specifically lies in this thematic, and focuses on the causes and consequences of epigenetic alterations in gliomas. These brain tumors can be divided into two subsets, based on IDH mutation status, that are characterized by different methylation profiles. Interestingly, the mutation of IDH is also associated with a better prognosis. Our strategy, based on exhaustive molecular analyses, relies on the study of 70 glioma samples, classified according to their IDH status, and of six glioblastoma stem cell (GSC) lines.We found that most transcriptional alterations in tumor samples were DNA methylation-independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between Polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Also, our study revealed that homeodomain genes, and in particular HOX genes, are characterized by an atypical defect in aggressive gliomas (IDHwt), associating a gain of expression with an aberrant gain of methylation. We determined that this alteration affect all the four HOX clusters, and that the reactivation of these genes is likely a consequence of the aberrant loss of H3K27me3 that specifically affect these clusters. This study allows to propose a model whereby global DNA hypomethylation triggers ectopic expression of numerous genes through a cascade of events, in which HOX gene alteration would have a central role.The observation that H3K27me3 is deregulated in gliomas, and particularly on HOX genes, also lead us to investigate for the role of non-coding RNA in these mechanisms. We have identified HOXA-AS2, a yet poorly characterized long non-coding RNA located at HOXA locus, that is specifically and significantly overexpressed in IDHwt gliomas. The inhibition of HOXA-AS2 in well-characterized CSG lines suggests that this transcript play a central role in the biology of these cells. Thus, it would contribute to the aggressiveness of CSG by inhibiting inflammatory pathways and promoting cell proliferation. Altogether, these works revisit the relationship between epigenetic alterations and aberrant transcription, and present the control of H3K27me3 as the main cause of transcriptionnel defects in cancer

APA, Harvard, Vancouver, ISO, and other styles

12

Fukuyama, Keita. "Gene expression profiles of liver cancer cell lines reveal two hepatocyte-like and fibroblast-like clusters." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/265181.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Hagihara, Takeshi. "Hydrodynamic stress stimulates growth of cell clusters via the ANXA1/PI3K/AKT axis in colorectal cancer." Kyoto University, 2020. http://hdl.handle.net/2433/253210.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Joseph, Anny-Claude. "Assessing the Impact of Incorporating Residential Histories into the Spatial Analysis of Cancer Risk." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5949.

Full text

Abstract:

In many spatial epidemiologic studies, investigators use residential location at diagnosis as a surrogate for unknown environmental exposures or as a geographic basis for assigning measured exposures. Inherently, they make assumptions about the timing and location of pertinent exposures which may prove problematic when studying long latency diseases such as cancer. In this work we explored how the association between environmental exposures and disease risk for long-latency health outcomes like cancer is affected by residential mobility. We used simulation studies conditioned on real data to evaluate the extent to which the commonly held assumption of no residential mobility 1) affected the ability of generalized additive models to detect areas of significantly elevated historic environmental exposure and 2) increased bias in the estimates of the relationship between environmental exposures and disease in a case-control study. While the literature suggests that some researchers have begun to develop methods to incorporate historic locations in studies of health outcomes, a number of questions remain. One reason for the knowledge gap is that residential histories have not been collected in most U.S. epidemiologic studies. In our work we evaluated the impact of using public-record database generated histories to estimate the effects of exposure in lieu of using subject-reported addresses collected during a study. Finally, we evaluated the effect of environmental exposure on cancer risk in a case-control study using an approach that combined a multiple membership conditional autoregressive (CAR) model with an environmental exposure index for temporally correlated time-varying exposure assigned based on residential histories. We used this model in a data application to explain bladder cancer risk in the New England Bladder Cancer Study. We included a temporal arsenic exposure index in the model to assess a large number of correlated arsenic exposures.

APA, Harvard, Vancouver, ISO, and other styles

15

Ivermark, Katarina. "Attacking cancer biomarker clusters from all sides : - bispecific, bivalent and polyspecific affinity proteins towards HER family receptors." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-292941.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Weston, William Christopher. "A SPATIAL ANALYSIS OF INVASIVE BREAST CANCER CLUSTERS IN ASSOCIATION WITH ENVIRONMENTAL RISK FACTORS: ILLINOIS 1996 TO 2000." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/theses/896.

Full text

Abstract:

This retrospective study assesses invasive breast cancer counts reported at the Illinois ZIP code scale during the study period of 1996 to 2000. The research objective is to evaluate the spatial and statistical associations between breast cancer risk and sources of potential environmental contamination. A thorough literature review illustrates a profound list of cancer risk factors within the study space. Public health principles are utilized to prepare breast cancer incidence for analysis, accompanied with the development of a case/control ecological model. Exploratory analyses suggest that breast cancer intensity is predominantly a rural problem. A generalized linear mixed model is employed, illustrating statistical associations between environmental risk factors and breast cancer risk. Coal Mines, Oil/Gas Wells, and Large Quantity Hazardous Waste Generators, display high statistical significance (p<0.001) in association with increased breast cancer risk. Unique socioeconomic attributes distinguish urban risk from rural risk, as can be seen in a discriminant function analysis. The modeling techniques utilized in this research display classic spatial epidemiological approaches that account for particular types of confounding effects, while also defining zones of disease risk through cluster detection. Results from this analysis are useful for future studies intended to account for epidemiological, clinical, chemical and biological disease-related information.

APA, Harvard, Vancouver, ISO, and other styles

17

Jurvilliers, Xavier. "Nanoparticules fonctionnalisées pour une vectorisation médicale active." Vandoeuvre-les-Nancy, INPL, 2003. http://www.theses.fr/2003INPL085N.

Full text

Abstract:

La première partie de ce travail décrit la préparation de nouveaux nanohybrides organique / inorganique destinés à la détection ainsi qu'à la destruction sélective de cellules cancereuses. La partie organique est notamment constituée d'acide folique qui joue le rôle de vecteur. Les récepteurs de ce composé sont, en effet, hyperexprimés à la surface de nombreuses cellules cancéreuses (mammaires, ovariennes et colorectales). L'unité inorganique est, quant à elle, composée de nanoparticules d'or de tailles, comprises entre 5 et 20 nm. Le lien entre ces deux fragments est assuré par un espaceur de la famille des aminothiols. La seconde partie de ce mémoire décrit la préparation de clusters d'or de morphologie contrôlée par réduction d'un sel d'or (+3) à l'aide d'un hydrure alcalin activé par un alcoolate. Il a notamment été montré que par un choix judicieux de l'hydrure (NaH ou LiH) et / ou du solvant de la réaction, il était possible d'accéder soit à des clusters sphériques d'une taille voisine de 2 nm, soit à des prismes d'or (aiguilles, triangles et hexagones)
The first part of this work describes the preparation of new organic/inorganic naanohybrids which are intended to be used for the detection and the selective destruction of cancer cells. We describe the synthetic methodology for covalent attachment of folie acid (organic moiety) to gold nanoparticles (inorganic moiety) sized between 5 and 20 mn. Aminothiols spacers were used for the linking of folic acid with gold particles. The second part describes the preparation of size-controlled gold clusters by reduction of gold (+3) bromide with an alkoxide activated hydride. We have demonstrated that an appropriate choice of hydride (NaH or LiH) end / or of the solvent used for the reduction allows either the preparation of 2 nm sized spherical gold clusters or gold nanoprisms (nanowires and polygonal shapes)

APA, Harvard, Vancouver, ISO, and other styles

18

Abduljawad, Suzan Fouad. "Fatigue-related Symptom Clusters and their Relationship with Depression, and Functional Status in Older Adults Hospice Patients with Cancer." Scholar Commons, 2018. https://scholarcommons.usf.edu/etd/7659.

Full text

Abstract:

The hospice care population with cancer are often older adults who report many cancer-related symptoms experienced often in clusters. Most prevalent of these symptoms is fatigue and often it co-occurs with depressive symptoms and poor physical functioning. This dissertation examined fatigue, symptom clusters, depression, physical activity, and functional status in older adults with cancer. The aims of the literature review were to understand the relationship among physical functioning, cancer fatigue, fatigue-related symptom clusters, and their relationship with functional status In older adults. The literature related to these associations is insufficient and inconclusive. The methods section aimed to investigate the reliability and validity of the Center for Epidemiology Studies-Depression scale, Boston Short Form (CESD-10). Using Structural Equation Modeling (SEM) for confirmatory factor analysis, the factor structure of responses in a cross-sectional sample (N = 200) of adults with different types and stages of cancer was examined. Internal consistency reliability estimate Cronbach’s alpha =0.737. The CESD-10 four-factor model (positive affect, depressive affect, somatic complaints, and interpersonal challenges) fits the data well. The CESD-10 was a valid and reliable measure for assessing depressive symptoms in this study. The final section examined fatigue related symptom clusters and their relationships with functional status in older adult hospice patients with cancer (N=519). The fatigue-related symptom cluster (lack of energy, feeling drowsy and lack of appetite), significantly predicted poor functional status. Experiencing physical and psychological symptoms has a significant impact on functional dependence. Hospice healthcare professionals should be alert to older adults’ symptom cluster experience during assessment and management.

APA, Harvard, Vancouver, ISO, and other styles

19

Guajardo, Olga A. "A critical assessment of geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee River, Michigan /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1594501451&sid=11&Fmt=2&clientId=1509&RQT=309&VName=PQD.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Bonaldi, Christophe. "Analyse de clusters sur le temps : application en carcinologie et en épidémiologie." Montpellier 1, 2003. http://www.theses.fr/2003MON1T017.

Full text

Abstract:

L'objectif de ce travail est de repondre a la problematique de l'analyse d'apparition d'evenements medicaux anormalement agreges dans le temps. Traditionnellement utilisee dans le cadre de la surveillance de maladies "rares" (leucemie infantile) ou d'etiologie meconnue (cancers), l'analyse de clusters est usuellement une premiere etape justifiant la recherche de facteurs de risque ou epidemiques. Des methodes statistiques ont ete developpees pour tester une tendance au regroupement des observations ou pour detecter la periode d'agregation et tester si cette derniere pouvait etre le fait du hasard. Nous proposons une revue exhaustive de ces methodes et nous essaierons de repondre a cette problematique en proposant une methode originale basee sur une regression puis en modelisant le taux du processus d'occurence des evenements par une methode de monte carlo par chaine de markov a sauts reversibles. L'ensemble de ces methodes est applique a des bases de donnees en carcinologie constituees par les registres des tumeurs de huit departemens francais.

APA, Harvard, Vancouver, ISO, and other styles

21

Di, Puma Salvatore Davide. "Progettazione sintesi e valutazione biologica dei lipopeptidi contenenti clusters multimerici dell'epitopo immunodominante pdtrp per l'immunoterapia attiva del cancro." Doctoral thesis, Università di Catania, 2012. http://hdl.handle.net/10761/1174.

Full text

Abstract:

During carcinogenesis MUC-1 cell-surface carbohydrates undergo incomplete glycosylation that causes exposure of highly immunodominant peptide PDTRP contained in the tandem repeat sequence of mucin core (GVTSAPDTRPAPGSTAPPAH). The incomplete glycosylation results also in the exposure of the normally cryptic carbohydrate antigens like Tn (GalNAc-O-Ser/Thr). In a previous work, we synthesized a macromolecular construct containing four unit of Tn antigen clustered onto a calix[4]arene scaffold bearing an immunoadjuvant moiety (P3CS). This construct gave in mice higher immune response when compared to monovalent reference compound, and the outlined data clearly showed a so called "cluster effect". The aim of this project was to synthesize multimeric lipopeptide constructs containing clusters of the PDTRP antigen assembled on calixarene scaffolds together with the immunoadjuvant tripalmitoyl-S-glyceryl-Cys-Ser (P3CS). The purpose was to investigate the role of the cluster effect in amplifying the antibody production with respect to a simple concentration increase of antigen units. In addition, the role of the scaffold flexibility was also examined using the relatively rigid tetrameric calix[4]arene and the more flexible calix[8]arene as platforms to realize the constructs. The PDTRP sequence was assembled by solid-phase peptide synthesis using Fmoc-protected amino acids in combination with Barlos s resin. The protected PDTRP-COOH was coupled via glycine spacer to calix[4]arene and calix[8]arene derivatives containing, at the upper rim, 4 and 8 glycine unit respectively, and, at the lower rim, 1 unit of P3CS. These calixarenes constructs were synthesized as previously reported in collaboration with CNR-ICB of Catania (Dr C. Geraci). The final constructs were characterized by 1H-NMR and MALDI-TOF. Five groups of six mice were immunized two times, at 1-week intervals, by intraperitoneal injections of the two synthesized constructs (0.030 micro mol/mouse) or the reference compound, Mono-PDTRP-P3CS, administered at three concentration levels (0.030, 0.120 and 0.240 micro mol/mouse). After 21 days from the first immunization antibodies specific to PDTRP antigen in sera were detected and quantified by end-point dilution ELISA. Mice immunized with the synthesized multimeric constructs showed a substantial and significant production of antibodies. For Octa-PDTRP-Gly-Calix[8]arene-P3CS and Tetra-PDTRP-Gly-Calix[4]-P3CS a significant (p<0.05) increase of the end-point titers of 32- and 8-fold were measured with respect to the mice group immunized using equimolar level of the reference monovalent construct. Even when the concentration of monovalent construct was increased 4- and 8-fold, in order to compare solutions with the same number of PDTRP antigen units, the reactivity elicited by octameric and tetrameric constructs were significantly higher (p < 0.05) with a 8- and 4-fold increase in the end-point titer values. The immunogenic response induced by the Octa-PDTRP-Gly-Calix[8]-P3CS was significantly higher (p<0.05) with respect to the tetrameric construct with an increase of 4-fold in the antibodies production. Novel, well-defined synthetic multivalent lipopeptide vaccine candidates have been designed and synthesized. All the multimeric constructs are able to induce specific PDTRP antibodies production in mice. The most active derivative is the Octa-PDTRP-Gly-Calix[8]-P3CS that ensure an activity double with respect to the tetrameric construct. In addition, the "cluster effect" observed is more evident for the octameric construct that is more flexible with respect to the calix[4]arene construct. The increased conformational flexibility could allow a better arrangement of PDTRP antigens array on the calix[8]arene scaffold, ensuring a good mimicking of the natural motif encountered in vivo in the cancer cells. This reveals perspectives for potential applications in cancer immunotherapy.

APA, Harvard, Vancouver, ISO, and other styles

22

Newman, Christopher Miles. "Randomised controlled trial to evaluate a direct referral service for investigation of patients with low risk sympton clusters suggestive of colorectal cancer, as against usual care." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431949.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Sundqvist, Martina. "Stability and selection of the number of groups in unsupervised clustering : application to the classification of triple negative breast cancers." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASM026.

Full text

Abstract:

Dans cette thèse, je traite, d'un point de vue statistique, le sujet de la classification des tumeurs du cancer du sein triple négatif (TNBC). Je me concentre principalement sur l'utilisation de la stabilité des clusters pour sélectionner le nombre de groupes dans le clustering, la méthode généralement utilisée pour la classification des TNBC. L'objectif de cette méthode est d'obtenir une classification robuste, c'est-à-dire facilement reproductible sur des données similaires.Malgré sa popularité, on sait encore peu de choses sur la façon dont cette méthode fonctionne. Pour cette raison, je propose deux contributions méthodologiques importantes : (1) un package R, clustRstab}, qui permet d'estimer, de manière flexible, la stabilité d'un clustering avec différents paramètres. Ce package est accompagné d'une étude de simulation et d'une étude d'application qui examine sous quelles conditions cette méthode fonctionne. (2) Une version modifiée de la version Ajusté du Rand Index (ARI), un score populaire pour les comparaisons de clusters, étape cruciale pour estimer la stabilité d'un clustering. Je corrige ce score en le basant sur une hypothèse de distribution multinomiale qui lui permet de prendre en compte la dépendance entre les clusters et de faire des inférences statistiques. Ce ARI modifié (M ARI) est implémenté dans le package R aricode. Ces deux méthodes sont ensuite appliquées à une large cohorte de tumeurs TNBC et les résultats sont discutés en relation avec des résultats des classification du TNBC de la littérature
In this thesis, I treat the topic of classifying Triple Negative Breast Cancer (TNBC) tumors from a statistical point of view. After proposing a classification of TNBC based on proteins, I mainly focus on the use of cluster stability for selecting the number of groups in unsupervised clustering. Indeed, this is the method generally employed when classifying TNBC. The aim of this method is to obtain a classification that is robust, that is, easily replicable on similar data. This is measured by its sensibility to small changes, such as subsamplig of the dataset.Despite the popularity of this method, little is still known about how or when it works. For this reason, I propose two important methodological contributions, increasing the usability and interpretability of this method: (1) an R-package, clustRstab, that easily enables to estimate the stability of a clustering in different parameter settings. This package is accompanied by a simulation and an application study investigating when and how this method works. (2) A Modified version of the Adjusted Rand Index (ARI), a popular score for cluster comparisons which is a crucial step for estimating the stability of a clustering. I correct this score by basing it on a multinomial distribution hypothesis which enables it to take into account dependence between clusterings and conduct statistical inference. This Modified ARI (M ARI) is implemented in the R package texttt{aricode}.These two methods are then applied to a large cohort of TNBC tumors and the results are discussed in relation to earlier classification results of TNBC

APA, Harvard, Vancouver, ISO, and other styles

24

Hassan, Sara. "Epithelial-mesenchymal plasticity in circulating tumour cells from patients with metastatic cancers and PDX models." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228621/8/Sara_Hassan_Thesis.pdf.

Full text

Abstract:

There is growing concern about the relevance of epithelial mesenchymal plasticity (EMP) status of primary tumours in influencing their metastatic potential. Circulating tumour cells (CTCs) provide a window into the metastatic process, and molecular characterisation of CTCs could lead to better understanding of the mechanisms involved in the metastatic cascade. This thesis is an investigation of molecular characteristics of EMP in tumours and CTCs using patient-derived xenograft models and patient blood samples. The CTC heterogeneity observed emphasises the complexity in CTC isolation and classification and supports the increasingly recognised importance of the epithelial-mesenchymal hybrid state in cancer progression and metastasis.

APA, Harvard, Vancouver, ISO, and other styles

25

Graffeo, Nathalie. "Méthodes d'analyse de la survie nette : utilisation des tables de mortalité, test de comparaison et détection d'agrégats spatiaux." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5067/document.

Full text

Abstract:

La survie nette, indicateur clé de l'efficacité des systèmes de soin dans la lutte contre le cancer, est un concept théorique représentant la survie que l'on observerait dans un monde hypothétique où le cancer étudié serait la seule cause de décès. En s'affranchissant de la mortalité due aux causes autres que ce cancer, elle permet des comparaisons entre populations. Dans cette thèse, après présentation du concept et des méthodes d'estimation de la survie nette quand la cause de décès est inconnue, nous étudions trois problématiques. La première porte sur les tables de mortalité utilisées pour estimer la survie nette. En France, ces tables sont stratifiées sur âge, sexe, année et département. Il serait intéressant d'utiliser des tables stratifiées sur d'autres facteurs impactant la mortalité. Nous étudions l'impact du manque de stratification sur les estimations des effets des facteurs pronostiques sur la mortalité en excès (celle due au cancer en l'absence des autres causes de décès) par des études de simulations et sur données réelles. La deuxième problématique porte sur la construction d'un test de type log-rank pour comparer des distributions de survie nette estimées par l'estimateur Pohar-Perme, estimateur non paramétrique consistant de la survie nette. Notre troisième problématique est de déterminer dans une aire géographique des zones différentes en termes de survie nette. Nous adaptons une méthode de détection de clusters à la survie nette en utilisant le test précédemment développé comme critère de découpage. Ce travail propose ainsi des développements et outils nouveaux pour étudier et améliorer la qualité de la prise en charge des patients atteints d'un cancer
In cancer research, net survival is a key indicator of health care efficiency. This theoretical concept is the survival that would be observed in an hypothetical world where the disease under study would be the only possible cause of death. In population-based studies, where cause of death is unknown, net survival allows to compare net cancer survival between different groups by removing the effect of death from causes other than cancer. In this work, after presenting the concept and the estimation methods of net survival, we focus on three complementary issues. The first one is about the life tables used in the estimates of net survival. In France, these tables are stratified by age, sex, year and département. Other prognostic factors impact on mortality. So it would be interesting to use life tables stratified by some of these factors. We study the impact of the lack of stratification in life tables on the estimates of the effects of prognostic factors on excess mortality by simulations and real data studies. In 2012, the Pohar-Perme estimator was proposed. It is a consistent non parametric estimator of net survival. The second issue involves the building of a log-rank type test to compare distributions of net survival (estimated by the Pohar-Perme estimator) between several groups. Our third issue is to propose a method providing potential spatial clusters which could contain patients with similar net cancer survival rates. We adapt a clustering method using the test we have built as a splitting criterion. This work proposes new developments and new tools to study and improve the quality of care for cancer patients. These methods are suitable to other chronic diseases

APA, Harvard, Vancouver, ISO, and other styles

26

Guo, Ling. ""Clustering categorical response" application to lung cancer problems in living scales." unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-04202008-163156/.

Full text

Abstract:

Thesis (M.S.)--Georgia State University, 2008.
Title from file title page. Jiawei Liu, Yu-sheng Hsu, committee co-chairs; Jeff Qin, committee member. Electronic text (82 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Aug. 20, 2008. Includes bibliographical references (p. 65-66).

APA, Harvard, Vancouver, ISO, and other styles

27

Weber, Erich. "Biochemical, immunological and functional characterization of the human small cell lung cancer related cell surface antigens cluster-1 (N-CAM CD56), cluster-4 (CD24) and cluster-5/5A /." [S.l.] : [s.n.], 1994. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10735.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Gu, Jin. "Statistical partition problem for exponential populations and statistical surveillance of cancers in Louisiana." ScholarWorks@UNO, 2014. http://scholarworks.uno.edu/td/1921.

Full text

Abstract:

In this dissertation, we consider the problem of partitioning a set of k population with respect to a control population. For this problem some multistage methodologies are proposed and their properties are derived. Using the Monte Carlo simulation techniques, the small and moderate sample size performance of the proposed procedure are studied. We have also considered at statistical surveillance of various cancers in Louisiana.

APA, Harvard, Vancouver, ISO, and other styles

29

Serier, Asma. "Étude de l’activité anti-tumorale des entérotoxines staphylococciques codées par l’enterotoxin gene cluster." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10171.

Full text

Abstract:

Du fait de leurs propriétés immunostimulantes, les entérotoxines de Staphylococcus aureus (SEs) sont aussi considérées comme des outils thérapeutiques anticancéreux potentiels. Cependant, leurs implications dans de nombreuses pathologies humaines limitent leurs utilisations. Récemment, un opéron dénommé enterotoxin gene cluster (egc) codant pour cinq entérotoxines (SEG, SEI, SElM, SElN et SElO) supposées être de moindre virulence pour l’organisme, a été mis en évidence. En 2004, des patients atteints de carcinome broncho-pulmonaire ont été traités par l’administration d’un surnageant de culture d’une souche de S. aureus, contenant l’opéron egc. Ce traitement a permis d’allonger la durée de survie, et n’a eu aucun effet secondaire. Dans ce cadre, l’objectif de cette thèse a été d’étudier l’activité anti-tumorale des toxines de l’egc. Nos travaux ont mis en évidence l’activité tumoricide de ces toxines, induite par l’activation du système immunitaire. Cette toxicité est médiée par la sécrétion de nombreux médiateurs solubles comme le TNF-α et le NO. Nous avons confirmé le caractère pro-inflammatoire de type Th1 des toxines de l’egc. Nos travaux ont également montré qu’hormis SEI, les toxines de l’egc induisent des sécrétions de cytokines, chimiokines, protéases matricielles (MMPs) et facteurs de croissances nettement inférieures à celle induites par le reste des SEs. Ces résultats pourraient expliquer la faible toxicité associée aux toxines de l’egc. Enfin, nous avons montré que SElO possèdent une toxicité intrinsèque vis-à-vis des lignées tumorales. Cette étude plaide en faveur de l'intérêt des toxines de l’egc dans le développement de nouvelles approches en thérapie anti-tumorale
The use of classical superantigens (e.g. SEA, SEB and SEC) for treatment of cancer has resulted in a low response rates due to serious toxicity in humans. However, in a recent clinical study, remarkable results in treating lung cancer were obtained using superantigens encoded by the enterotoxin gene cluster (egc) without causing any significant toxicity. The current study was performed to investigate how egc superantigens (i.e. SEG, SEI, SElM, SElN and SElO) have tumoricidal activity with low toxicity. Indeed, we first demonstrated that tumoricidal activity of egc-SEs is mediated by immune cell activation, in particular, by secretion of soluble mediators such as nitric oxide and TNF-α. Thus, the proteomic analysis of the PBMC supernatants, showed that SEs-egc enhance the expression of pro-inflammatory cytokines, chimokines and many other biomarkers. Interestingly, levels were significantly higher in supernatants of SEA-stimulated PBMC than those with egc superantigens suggesting that staphylococcal superantigens differs in their inflammatory proprerties. Our results suggest that the relative lower pro-inflammatory activity of egc toxins may explain the low toxicity of these toxins observed during the clinical trial. Finally, we showed that SElO have a direct cytostatic activity against tumor cells. These findings suggest that egc-SEs seems to be good candidates for the development of new drugs in cancer therapy

APA, Harvard, Vancouver, ISO, and other styles

30

Al-Hinnawi, Abdel-Razzak. "Computer aided detection of clustered micro-calcifications in the digitised mammogram." Thesis, University of Aberdeen, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301076.

Full text

Abstract:

The presence of distributed micro-calcifications can be an indicator of early breast cancer. On the mammogram, they appear as bright smooth particles superimposed on the normal breast image background. Radiologists determine the occurrence of this lesion by detecting the individual micro-calcifications and then examining their distribution within the breast tissue. Due to the visual complexity of the mammogram, the detection sensitivity is usually less than 100%. The digital environment has the potential to increase the radiologist's accuracy. We have developed a computer aided detection (CAD) scheme that can identify clinically indicative clusters of micro-calcifications. The CAD algorithm emulates some aspects of the radiologists' approach by using contrast texture energy segmentation and morphological distribution analysis. On a local database of 61 mammograms digitised at 100μm with 8 bits intensity resolution, the CAD returns: a) 85% sensitivity (91% for malignant lesions and 78% for those that are benign), b) 0.33 false positive clusters (FPC) per image and c) 92% specificity. Therefore, the output from the CAD is shown to compare favourably with the performance of an expert radiologist. It also compares favourably with other CAD techniques, exceeding many algorithms which employ a higher level of mathematical complexity. The scheme is tested on an international database provided by the Mammographic Image Analysis Society. In this case it returns a) 96.4% sensitivity (100% for malignant lesions and 92% for those that are benign) b) 2.35 FPC rate per image and c) 33% specificity. The higher FPC rate is attributed to the different acquisition and production of the digital mammograms. It is concluded that this can be reduced by employing a shape analysis procedure to the CAD's final output. It is shown that the image processing principles we have implemented are generally successful on databases which are produced at other centres under different technical conditions.

APA, Harvard, Vancouver, ISO, and other styles

31

Meddis, Alessandra. "Inference and validation of prognostic marker for correlated survival data with application to cancer." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASR005.

Full text

Abstract:

Les données de survie en grappes sont souvent recueillies dans le cadre de la recherche médicale. Elles sont caractérisées par des corrélations entre des observations appartenant à un même groupe. Ici, nous discutons des extensions a des données en grappes dans différents contextes : évaluation de la performance d'un biomarqueur candidat, et l’estimation de l'effet du traitement dans une méta-analyse sur données individuels (IPD) avec risques concurrents. La première a été motivée par l'étude IMENEO, une méta-analyse où l'intérêt portait sur la validité pronostique des cellules tumorales circulantes (CTCs). Notre objectif était de déterminer dans quelle mesure les CTCs discriminent les patients qui sont morts de ceux qui ne l'ont pas fait dans les t-années, en comparant des individus ayant le même stade de tumeur. Bien que la courbe ROC dépendante du temps ait été largement utilisée pour la discrimination des biomarqueurs, il n'existe pas de méthodologie permettant de traiter des données en grappes censurées. Nous proposons un estimateur pour les courbes ROC dépendantes du temps et pour l'AUC lorsque les temps d'évènements sont correlés. Nous avons employé un modèle de fragilité partagée pour modéliser l'effet des covariables et du biomarqueur sur la réponse afin de tenir compte de l'effet de la grappe. Une étude de simulation a été réalisée et a montré un biais négligeable pour l'estimateur proposé et pour un estimateur non paramétrique fondé sur la pondération par la probabilité inverse d’être censuré (IPCW), tandis qu'un estimateur semi-paramétrique, ignorant la structure en grappe est nettement biaisé.Nous avons également considéré une méta-analyse IPD pour quantifier le bénéfice de l'ajout de la chimiothérapie à la radiothérapie sur chaque risque concurrent pour les patients avec un carcinome nasopharyngien . Les recommandations pour l'analyse des risques concurrents dans le cadre d'essais cliniques randomisés sont bien établies. Étonnamment, aucune recommendation n'a encore été proposée pour l’anlayse d'une méta-analyse IPD avec les risque concurrents. Pour combler cette lacune, ce travail a détaillé la manière de traiter l'hétérogénéité entre les essais par un modèle de régression stratifié pour les risques concurrents et il souligne que les mesures standardes d'hétérogénéité pour évaluer l'incohérence peuvent facilement être utilisées. Les problèmes typiques qui se posent avec les méta-analyses et les avantages dus à la disponibilité des caractéristiques au niveau du patient ont été soulignées. Nous avons proposé une approche landmark pour la fonction d'incidence cumulée afin d'étudier l'impact du temps de suivi sur l'effet du traitement.L'hypothèse d'une taille de grappe non informative était faite dans les deux analyses. On dit que la taille de grappe est informative lorsque la variable réponse dépend de la taille de grappe conditionnellement à un ensemble de variables explicatives. Intuitivement, une méta-analyse répondrait à cette hypothèse. Cependant, la taille de grappe non informative est généralement supposée, même si elle peut être fausse dans certaines situations, ce qui conduit à des résultats incorrects. La taille des grappes informatives (ICS) est un problème difficile et sa présence a un impact sur le choix de la méthodologie. Nous avons discuté plus en détail de l'interprétation des résultats et des quantités qui peuvent être estimées et dans quelles conditions. Nous avons proposé un test pour l'ICS avec des données en grappes censurées. À notre connaissance, il s'agit du premier test sur le contexte de l'analyse de survie. Une étude de simulation a été réalisée pour évaluer la puissance du test et quelques exemples sont fournis à titre d'illustration.L'implémentation de chacun de ces développements est disponible sur https://github.com/AMeddis
Clustered data often arises in medical research. These are characterized by correlations between observations belonging to the same cluster. Here, we discuss some extension to clustered data in different contexts: evaluating the performance of a candidate biomarker, and assessing the treatment effect in an individual patient data (IPD) meta-analysis with competing risks. The former was motivated by the IMENEO study, an IPD meta-analysis where the prognostic validity of the Circulating Tumor Cells (CTCs) was of interest. Our objective was to determine how well CTCs discriminates patients that died from the one that did not within the t-years, comparing individuals with same tumor stage. Although the covariate-specific time dependent ROC curve has been widely used for biomarker's discrimination, there is no methodology that can handle clusteres censored data. We proposed an estimator for the covariate-specific time dependent ROC curves and area under the ROC curve when clustered failure times are detected. We considered a shared frailty model for modeling the effect of the covariates and the biomarker on the outcome in order to account for the cluster effect. A simulation study was conducted and it showed negligible bias for the proposed estimator and a nonparametric one based on inverse probability censoring weighting, while a semiparametric estimator, ignoring the clustering, is markedly biased.We further considered an IPD meta-analysis with competing risks to assess the benefit of the addition of chemotherapy to radiotherapy on each competing endpoint for patients with nasopharyngeal carcinoma. Recommendations for the analysis of competing risks in the context of randomized clinical trials are well established. Surprisingly, no formal guidelines have been yet proposed to conduct an IPD meta-analysis with competing risk endpoints. To fill this gap, this work detailed: how to handle the heterogeneity between trials via a stratified regression model for competing risks and it highlights that the usual metrics of inconsistency to assess heterogeneity can readily be employed. The typical issues that arise with meta-analyses and the advantages due to the availability of patient-level characteristics were underlined. We proposed a landmark approach for the cumulative incidence function to investigate the impact of follow up on the treatment effect.The assumption of non informative cluster size was made in both the analyses. The cluster size is said to be informative when the outcome depends on the size of the cluster conditional on a set of covariates. Intuitively, a meta-analysis would meet this assumption. However, non informative cluster size is commonly assumed even though it may be not true in some situations and it leads to incorrect results. Informative cluster size (ICS) is a challenging problem and its presence has an impact on the choice of the correct methodology. We discussed more in details interpretation of results and which quantities can be estimated under which conditions. We proposed a test for ICS with censored clustered data. To our knowledge, this is the first test on the context of survival analysis. A simulation study was conducted to assess the power of the test and some illustrative examples were provided.The implementation of each of these developments are available at https://github.com/AMeddis

APA, Harvard, Vancouver, ISO, and other styles

32

Sakr, Lama. "Phenotypic heterogeneity of potentially curable non-small cell lung cancer: cohort study with cluster analysis." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116984.

Full text

Abstract:

Background: The Tumor, Node, Metastasis (TNM) staging system in non-small cell lung cancer (NSCLC) is currently the most reliable prognostic tool. However, significant differences in clinical course and outcome are observed among patients with apparent curable disease by TNM staging. A more elaborate classification system that simultaneously incorporates the various facets of NSCLC may help identify specific disease patterns, therefore providing a more reliable prediction of outcome. Objectives: 1) to classify patients with potentially curable NSCLC into distinct phenotypic groups using cluster analysis, a multivariate statistical technique. 2) To validate the clinical relevance of these phenotypic clusters by assessing their differences with regard to outcome. Methods: A review of prospectively-collected data from stage I-III NSCLC patients, seen in a single hospital-based centre between January 2004 and October 2010, was conducted. Multiple correspondence analysis (MCA) was applied on a number of baseline variables, and followed by hierarchical clustering using Ward's linkage method. . Overall and disease-free survival estimates were compared among clusters using Kaplan-Meier curves and Cox proportional hazards modeling. Results: The total cohort (n=367) and a surgical sub-cohort (n=169) of patients with early-stage surgically resected NSCLC were analysed. In the total cohort, four and three-cluster models were identified to classify the patients. Clusters were distinct from each other, mainly with respect to gender distribution, smoking status, disease stage, degree of histologic differentiation- and to some extent histologic subtype- tumour metabolic activity on PET, and thyroid transcription factor 1 staining on immunohistochemistry. The surgical sub-cohort was also best classified using four or three-cluster algorithms. Clusters were determined on the basis of the previously cited variables, as well as EGFR mutational status and microscopic vascular and visceral pleural invasion. Overall and disease-free survival estimates differed significantly among various clusters in both the total cohort and surgical sub-cohort. Adjustment for age did not affect results significantly. Conclusion: Cluster analysis allowed the identification of distinct NSCLC phenotypes that exhibit differences in disease presentation, clinical course and outcome.
Contexte: La classification TNM dans le cancer bronchique non à petites cellules (CBNPC) est actuellement le meilleur outil pronostique. Cependant, une hétérogénéité significative quant à la présentation et l'évolution clinique de la maladie est observée chez les patients dont le stade est potentiellement curable. Un système de classification plus élaboré, incorporant de façon simultanée plusieurs aspects de la maladie, permettrait d'identifier certains profils distincts du CBNPC, et ainsi offrir une meilleure prédiction de l'évolution clinique. Objectifs : 1) Classifier les patients avec CPNPC en phénotypes distincts, à l'aide de l'analyse de partitionnement de données (APD)- une technique statistique multi-variée. 2) Valider la pertinence clinique de ces phénotypes en comparant l'évolution clinique de chacun. Méthodes : Une revue de données prospectives sur les patients avec CBNPC stades I- III, diagnostiqué entre Janvier 2004 et Octobre 2010, a été effectuée. L'analyse des correspondances multiples a été appliquée sur un ensemble de variables de base, et suivie d'une APD hiérarchique utilisant la méthode de Ward. Des analyses de survie ont été effectuées à l'aide de la technique Kaplan-Meier. Les paramètres de survie globale et de survie sans progression ont été comparés entre les différents phénotypes, en ayant recours au modèle à risques proportionnels de Cox. Résultats: La cohorte complète (n= 367), ainsi qu'une sous-cohorte chirurgicale (n=169), ont été analysés. Dans la cohorte complète, un modèle de partitionnement de données à 3 ou 4 groupes est illustré. Les phénotypes se distinguaient par la distribution des sexes, tabagisme, stade de la maladie, degré de différentiation- et parfois le sous-type histologique- activité métabolique de la tumeur, et l'expression du facteur de transcription thyroïdienne en analyse immunohistochimique. La sous-cohorte chirurgicale était également représentée par un modèle de partition en 3 ou 4 groupes, se démarquant par les facteurs décrits ci-haut, en plus du statut de l'EGFR et l'invasion microscopique vasculaire et de la plèvre viscérale. Les paramètres de survie globale et sans progression différaient de façon significative entre les phénotypes établis, et ce, dans les deux cohortes. L'ajustement pour l'âge n'a pas modifié les résultats de façon notable. Conclusion: L'APD permet l'identification de phénotypes distincts de CBNPC, ayant des différences importantes quant à la présentation et l'évolution clinique de la maladie.

APA, Harvard, Vancouver, ISO, and other styles

33

Nguyen, Ly Thuy. "A psycho-educational intervention for symptom cluster management among cancer patients undergoing treatment in Vietnam." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/116352/1/Ly%20Thuy_Nguyen_Thesis.pdf.

Full text

Abstract:

This thesis is the first to explore self-management interventions for patients experiencing cancer related symptoms in Vietnam. The study represents one of the few trials of psycho-educational symptom cluster interventions across the world. Findings provide preliminary evidence supporting the role of psycho-educational interventions in reducing the impact of the cancer related symptom cluster comprising fatigue, pain and sleep disturbance.

APA, Harvard, Vancouver, ISO, and other styles

34

Lau, Sze-hang Billy, and 劉思行. "Identification and characterization of key genes involved in the development and progression of hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39346924.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Bravi, F. "DIETARY PATTERNS AND ESOPHAGEAL CANCER: A POSTERIORI DIETARY PATTERNS IDENTIFIED THROUGH FACTOR ANALYSIS AND CLUSTER ANALYSIS." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/215074.

Full text

Abstract:

Background: Because of the complexity of diet and the potential interactions between dietary components, the use of dietary patterns has been proposed, to describe variations in overall dietary intakes in a specific population and to analyze the relationship between diet and cancer risk. In the present work, factor analysis and cluster analysis were used in combination to identify groups of subjects with similar dietary patterns. Patients and methods: We analyzed data from an Italian case–control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. A varimax rotation was applied to achieve a simpler loading structure. Nutrients with absolute rotated factor loading greater or equal to 0.63 on a given pattern were used to name the patterns. For each pattern, participants were grouped into categories according to quartile of factor scores among the control population, and the odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models accounting for potential confounding variables. Then, cluster analysis was performed on factor scores obtained from factor analysis. The main analysis was carried out using the k-means method with Euclidean distance. The initial seeds were obtained performing preliminarily a hierarchical method (Ward’s) and cutting the resulting dendrogram at the level corresponding to 6 clusters. Results from the main analysis were compared with those from other clustering solutions identified using the k-means method with Manhattan, Lagrange and Correlation coefficient similarity measure distances and the Partitioning around Medoids method, with both Euclidean and Manhattan distances. The identified clusters were characterized by examining the distribution of several sociodemographic and lifestyle variables, and the average consumption of selected nutrients and food groups, within cluster. The ORs were estimated for each of the identified clusters, and corresponding 95% CIs were obtained referring to the floating absolute risks method. Results: PCFA allowed to identify five major dietary patterns, which explained about 80% of the total variance in the original nutrients. The Animal products and related components pattern (with high factor loadings on calcium, phosphorus, riboflavin, animal protein, saturated fatty acids, cholesterol, and zinc) was positively related to esophageal cancer risk (OR=1.64, 95% CI: 1.06-2.55). The Vitamins and fiber (with high loadings on vitamin C, total fiber, beta-carotene equivalents, soluble carbohydrates, and total folate) and the Other polyunsaturated fatty acids and vitamin D (with high loadings on other polyunsaturated fatty acids, vitamin D, and niacin) were inversely related to esophageal cancer (OR=0.50, 95% CI: 0.32-0.78, and OR=0.48, 95% CI: 0.31-0.74, respectively), while no relationship with this cancer was observed for the Starch-rich (starch, vegetable protein, and sodium) characterized by high loadings on (OR=0.80, 95% CI: 0.50-1.28) and the Other fats (with high loadings on linoleic acid, linolenic acid, and vitamin E) patterns (OR=1.04, 95% CI: 0.67-1.63). The naming of the factors, based on high factor scores characterizing each pattern, was confirmed by the distributions of selected nutrients and food groups. The subsequent cluster analysis, based on differences in the dietary patterns, yielded 6 clusters, one of which (C3) was characterized by the lowest intakes of all nutrients and food groups considered, while the remaining clusters were determined by an extreme value of the dietary patterns, one-by-one. Subjects in the C1 cluster were characterized by the highest values of the Vitamins and fiber pattern, subjects in the C2 cluster had the highest values of the Other polyunsaturated fatty acids pattern, the C4 cluster was characterized by the highest scores of the Animal products and related components, subjects in the C5 cluster had the highest values of the Other fats pattern, the C6 cluster was characterized by the highest scores of the Starch-rich pattern and had the highest intakes of bread, and pasta and rice. Significant inverse relations were observed between the C1, C5 and C6 clusters (OR=0.59, 95% CI:0.40-0.88, OR=0.42, 95% CI:0.20-0.86, and OR=0.60, 95% CI: 0.42-0.86, respectively) – which were characterized by high values of the Vitamins and fiber, Other fats, and Starch-rich patterns, respectively – as compared to the C3 cluster. No significant risk was observed for the C2, and C4 clusters (OR=0.76, 95% CI: 0.51-1.13, and OR=1.29, 95% CI: 0.80-2.07). Conclusion: The combined application of factor and cluster analyses, allows to identify key dietary aspects in a specific population, and to obtain mutually exclusive groups of subjects who are similar for these characteristics. The two techniques have limitations that arise from the subjective decisions involved in the analyses. In this application, various alternative options were tried, to check robustness and solution stability. Among these complementary analyses, results from PCFA were compared with those from another principal axis factoring, and those from PCFA analyses performed separately in strata of center and gender, and in randomly generated split samples. Moreover, the internal consistency of the identified patterns was evaluated using the Cronbach’s coefficient alphas. All these checks supported the decisions adopted in the main analyses. As concern cluster analysis, to limit the influence of the starting point, the initial seeds used in the k-means method were obtained performing a hierarchical clustering (Ward’s method) and cutting the corresponding dendrogram at the level k=6. Moreover, some alternative solutions were identified through different methods and distances, yielding comparable clustering solutions. Another limitation of cluster analysis is its sensitivity to the presence of outliers; however, the exclusion of 8 potential outliers did not materially change the results.

APA, Harvard, Vancouver, ISO, and other styles

36

Glackin, A. J. "The synergy of gemcitabine with clusterin antisense oligonucleotides in the treatment of bladder cancer." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426981.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

So, Kwok-Wei. "The symptom cluster of fatigue, pain and psychological distress and its impact on the quality of life in Chinese patients with breast cancer undergoing cancer treatment /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

Find full text

Abstract:

Thesis (Ph.D. in Nursing) -- University of Colorado Denver, 2007.
Typescript. Includes bibliographical references (leaves 168-181). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

APA, Harvard, Vancouver, ISO, and other styles

38

Sakiragaoglu, Onur. "Strategies for Knockdown of Gene Products That Promote Cancer Growth." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/366861.

Full text

Abstract:

Cancer is second only to cardiovascular disease in the number of deaths every year and millions of deaths are caused by cancer globally. Current therapies for many cancers are still not sufficient to achieve a long term cure. One of the important hallmarks of cancer is rapid cell division. Another hallmark of cancer is avoidance of senescence. Telomere stabilisation facilitates rapid cell division and is one of various factors that contribute to the avoidance of senescence. Telomeres are tandemly repeated sequences found at the end of eukaryotic chromosomes. Telomerase is an enzyme complex that extends telomeric repeat sequences, protects cells from senescence and has a major role in the acquisition of high proliferative potential by cancer cells. Thus, down-regulation of expression of the catalytic subunit of telomerase may be an effective way to treat cancer. Interventions that target cancer metabolism can also prevent proliferation of cancer cells. Downregulation of expression or complete silencing of expression of those genes which encode products that are essential for cancer metabolism is one of the key future strategies for cancer treatment. In this regard, the products of genes including lactate dehydrogenase A (LDHA), monocarboxylate transporter 1 (MCT1), cluster of differentiation 147 (CD147) and pyruvate kinase isoenzyme 2 (PKM2) are critically required for aerobic glycolysis and are possible targets for cancer therapy. Upregulation of expression of these gene products favours tumour progression. Thus, silencing the expression of these gene products may provide a non-conventional approach for cancer treatment.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text

APA, Harvard, Vancouver, ISO, and other styles

39

Wells, Kristen. "The Development and Use of a Geographic Information System for Evaluating the Association between Pesticide Exposure and Prostate Cancer." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2243.

Full text

Abstract:

Abstract 1 – A Geographic Information System for Evaluating Residential Pesticide Exposure and Prostate Cancer Incidence Agricultural pesticide exposure is hypothesized to be a risk factor for prostate cancer, and such exposures are of particular concern for men living in farming communities where large-scale pesticide applications occur. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006, and county and census tract level age-adjusted incidence rates were calculated. Historical crop-specific land use records and pesticide sales data for the state of Iowa during 1990 were integrated into a geographic information system (GIS), where estimates of predicted exposure to the four most commonly used pesticides in Iowa (atrazine, metolachlor, cyanazine, alachlor) were produced. Ecological correlation between pesticide exposure and prostate cancer incidence was evaluated using Spearman’s (rank) correlation coefficient and linear regression analysis. Statistically significant associations between prostate cancer incidence and percent of acres of corn and soybean crops were found at both the county (r=0.22, p=.031 and r=0.33, p=.001, respectively) and census tract (r=0.10, p=.007 and r=0.13, p<.001, respectively) level. The associations between percent of land exposed to the specific pesticides and prostate cancer were not statistically significant. Our findings suggest that residential proximity to corn and soybean fields, and by association the pesticides used on those crops, is correlated with increased prostate cancer risk, but that the increase in risk is not correlated with exposure to the four most commonly used pesticides in Iowa in 1990. Findings from this study underscore the need for continued investigation of the association between agricultural exposures and prostate cancer incidence. Abstract 2 – Spatial Analysis of Prostate Cancer Incidence and Residential Pesticide Exposure in Iowa A statistically significant positive association between prostate cancer incidence and residential proximity to corn and soybean fields in Iowa exists. Research suggests that exposure to pesticides used on these crops increases prostate cancer risk. The objective of this study was to investigate clustering of prostate cancer risk in the presence of potential exposure to pesticides in Iowa. Prostate cancer incidence data (1996-2006) were obtained from the State Health Registry of Iowa. Using SaTScan software, clusters of high and low prostate cancer risk were identified. Ecological correlation between exposure to the four most commonly used pesticides (atrazine, metolachlor, cyanazine, alachlor) in Iowa during 1990 and residence in a cluster of relatively high or low prostate cancer incidence was evaluated using Pearson’s chi-square test statistic and logistic regression analysis. Clusters of increased prostate cancer risk were associated with a greater percentage of land used for all crops of interest (i.e., corn and soybean farming (p <0.001), corn farming (p <0.001), soybean farming (p <0.001)) and low exposure to alachlor (p =0.032) than did clusters with decreased risk of prostate cancer. After adjustment for percent of land used for each crop type, no association between pesticide exposure and prostate cancer risk was observed. Residence in or near agricultural communities increases prostate cancer risk. Our findings suggest that residential proximity to exposures specific to corn and soybean farming increases prostate cancer risk. Evaluation of exposure to less commonly used pesticides and those used in lower quantities is needed. Abstract 3 – Multilevel Analysis of Residential Pesticide Exposure and Prostate Cancer Incidence An association between residential exposure to factors specific to corn and soybean farms in Iowa exists. The objectives of this study were to statistically assess spatial autocorrelation in prostate cancer incidence in Iowa and to evaluate the effect of residential exposure to the most commonly used pesticides for corn and soybean farms in Iowa in 1990 on prostate cancer incidence. Prostate cancer incidence data were obtained from the State Health Registry of Iowa for the years 1996 through 2006. Spatial patterning of age-adjusted incidence rates was assessed via Moran’s I global index of spatial autocorrelation. A hierarchical regression modeling approach with an assumed Poisson distribution was used to characterize the relationship between census tract level prostate cancer incidence and exposure to pesticides. Statistically significant spatial patterning of prostate cancer incidence, corn and soybean fields and pesticide use (p<.001 for all variables) was observed. After adjustment for individual and area level characteristics, prostate cancer risk increased by approximately 25% for each percentage point increase in percent of land used for corn and soybean crops. Prostate cancer risk was approximately 25% higher for Black men exposed to corn and soybean fields compared to white men exposed to corn and soybean fields. Results from this study support the need for further evaluation of residential exposure to environmental hazards specific to corn and soybean farming.

APA, Harvard, Vancouver, ISO, and other styles

40

Kulasinghe, Arutha Jeevana. "Circulating tumour cells in head and neck cancers." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/110534/1/Arutha%20Jeevana_Kulasinghe_Thesis.pdf.

Full text

Abstract:

Metastasis in head and neck cancer patients is responsible for over 50% of deaths. There are currently no tools to identify patients at risk of developing metastasis. Circulating tumour cells (CTC) represent a transient cancer cell population in the blood. In this study, the researcher has developed CTC isolation methodologies and used novel culture formulations to expand patient derived CTCs for therapy testing. Furthermore, the researcher identified biomarkers present on CTCs which could select patients for immunotherapies, a current unmet need. This work sets the foundation for a personalized medicine approach to treating head and neck cancer patients.

APA, Harvard, Vancouver, ISO, and other styles

41

Maloney, Stephanie Louise. "An investigation into the regulation and expression of the tumour suppressor gene clusterin in oral, cervical and nasopharyngeal cancer." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/612/.

Full text

Abstract:

Clusterin (CLU) is a multifunctional glycoprotein widely expressed as two isoforms. One isoform, sCLU is secreted, cytoplasmic and anti-apoptotic, the other, nCLU, is nuclear and pro-apoptotic. Seven genes, DKK3, TIMP1, CADM1, AKAP12, KLF4, RNASET2 and CLU were identified to be candidate tumour suppressor genes in cervical neoplasia and subsequent validation led to an evaluation of the regulation and expression of CLU at three sites of squamous cancer: the oral cavity, cervix and nasopharynx. Down-regulation of CLU was demonstrated in nasopharyngeal cancer (NPC) and oral cancer and loss of one CLU allele and methylation of the other in the NPC cell line C666-1. This defect has been repaired in this NPC cell line and showed that overexpression of the nuclear isoform of CLU resulted in reduced proliferation and decreased cell viability. Overexpression of both isoforms of CLU in C666-1 cells and their knockdown in HeLa cells regulates NF-kB activity, with a stabilisation of IkB\(\alpha\) following CLU overexpression in C666-1. Although sCLU is now considered a promising therapeutic target because of its anti-apoptotic function, with an antisense oligonucleotide currently undergoing clinical evaluation, results suggest that further consideration needs to be given to the possible tumour suppressor function of nCLU.

APA, Harvard, Vancouver, ISO, and other styles

42

Fuziwara, Cesar Seigi. "O cluster de microRNAs miR-17-92 e seus alvos na oncogênese tiroidiana: influência de BRAFT1799A e de iodo." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-19112014-162309/.

Full text

Abstract:

O excesso de iodo inibe a proliferação celular e secreção hormonal, enquanto retarda os efeitos oncogênicos da ativação de RET/PTC3 na célula folicular tiroidiana. A mutação BRAF (T1799A) é a mais prevalente no câncer de tiroide, e modelo transgênico desenvolve câncer que progride para histotipo agressivo. Altos níveis de microRNAs (miRNAs) do cluster miR-17-92 estão associados a histotipos agressivos de câncer de tiroide e modulam a tradução de mRNAs alvo componentes de vias de sinalização oncogênicas. Neste estudo, avaliamos a influência da alta dose de iodo sobre miRNAs frente ativação do oncogene BRAF e seu efeito na biologia da célula folicular tiroidiana. A indução de BRAFT1799A ativa uma robusta expressão de miR-17-92 enquanto alta dose de iodo bloqueia este efeito na célula tiroidiana. miR-19 inibe a tradução de Smad4 e bloqueia a transdução do sinal de TGFb, efeito revertido pelo iodo. O iodo interfere na expressão de miR-17-92 por bloquear ativação da sinalização Notch induzida por BRAF. Estes resultados indicam que o iodo protege a célula folicular tiroidiana durante a indução de BRAFT1799A, revertendo a ativação dos miRNAs oncogênicos do cluster miR-17-92 e restaurando os níveis protéicos de Smad4 por interferir na via de sinalização Notch.
Iodine excess blocks cell proliferation and inhibits hormone synthesis, while delays oncogenic effects of RET/PTC3 activation in thyroid follicular cells. BRAF mutation (T1799A) is the most prevalent genetic alteration in thyroid cancer, and transgenic mice model for BRAF develops thyroid cancer that progress to aggressive histotypes. High levels of microRNAs (miRNAs) of miR-17-92 cluster are associated to aggressive thyroid cancer and modulate translation of target mRNAs in oncogenic signaling pathways. In this study, we evaluated the influence of high dose iodine in miRNAs under BRAF oncogene activation, and its effects in thyroid follicular cell biology. BRAF induction induces high expression of miR-17-92 while high dose iodine blocks this effect in thyroid follicular cells. miR-19 inhibits Smad4 translation and impairs TGFb signaling transduction, effect reverted by iodine. Iodine modulates miR-17-92 expression by interfering in BRAF-induced Notch signaling activation. These results indicate that iodine protects thyroid follicular cell during BRAF induction, reverting oncogenic miR-17-92 activation and restoring protein levels of Smad4 by Notch signaling modulation.

APA, Harvard, Vancouver, ISO, and other styles

43

Ronquist, Göran. "Some Characteristics of Human Prostasomes and Their Relationship to Prostate Cancer." Doctoral thesis, Uppsala universitet, Klinisk kemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100799.

Full text

Abstract:

Background: The secretory epithelial cells of the prostate gland use sophisticated vehicles named prostasomes to relay important information to sperm cells in semen. This prostasome-forming and secretory ability of the epithelial cells is also preserved in poorly differentiated prostate cancer cells. Aim: The aim of this thesis was to examine different characteristics of prostasomes, especially those derived from malignant prostate cells, linked to their potential role in diagnosis and prognostication of prostate cancer. Results: Serum samples of prostate cancer patients contained autoantibodies against seminal prostasomes in a higher concentration than did control sera. These autoantibodies were most frequently directed against 25 prostasome-associated proteins, but no one was prostate specific. Clusterin was one of the most frequently occurring prostasomal proteins. Elevated titers were however seen in both patients´ and control sera. Clusterin turned out to be a major antigen of seminal prostasomes. No prostate specific or prostate cancer specific protein was discovered upon proteomic analysis of prostasomes deriving from malignant cells of vertebral metastases of prostate cancer patients. Human chromosomal DNA was identified in both seminal prostasomes and PC-3 cell prostasomes and strong evidence existed that the DNA was localized inside the prostasomes. Four out of 13 DNA clones of seminal prostasomes featured gene sequences (31%). The corresponding figures for PC-3 cell prostasomes were 4 out of 16 clones (25%). Conclusions: Prostasomes are immunogenic and give rise to serum autoantibodies. The most frequently occurring autoantibodies were directed against 25 prostasomal proteins but none of these was exclusively prostate specific. Thirty different proteins were identified in prostate cancer metastasis-derived prostasomes but none of these proteins was prostate cancer specific. Human chromosomal DNA was identified in prostasomes of both normal and malignant cell origin.

APA, Harvard, Vancouver, ISO, and other styles

44

Kuang, Da. "Nonnegative matrix factorization for clustering." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/52299.

Full text

Abstract:

This dissertation shows that nonnegative matrix factorization (NMF) can be extended to a general and efficient clustering method. Clustering is one of the fundamental tasks in machine learning. It is useful for unsupervised knowledge discovery in a variety of applications such as text mining and genomic analysis. NMF is a dimension reduction method that approximates a nonnegative matrix by the product of two lower rank nonnegative matrices, and has shown great promise as a clustering method when a data set is represented as a nonnegative data matrix. However, challenges in the widespread use of NMF as a clustering method lie in its correctness and efficiency: First, we need to know why and when NMF could detect the true clusters and guarantee to deliver good clustering quality; second, existing algorithms for computing NMF are expensive and often take longer time than other clustering methods. We show that the original NMF can be improved from both aspects in the context of clustering. Our new NMF-based clustering methods can achieve better clustering quality and run orders of magnitude faster than the original NMF and other clustering methods. Like other clustering methods, NMF places an implicit assumption on the cluster structure. Thus, the success of NMF as a clustering method depends on whether the representation of data in a vector space satisfies that assumption. Our approach to extending the original NMF to a general clustering method is to switch from the vector space representation of data points to a graph representation. The new formulation, called Symmetric NMF, takes a pairwise similarity matrix as an input and can be viewed as a graph clustering method. We evaluate this method on document clustering and image segmentation problems and find that it achieves better clustering accuracy. In addition, for the original NMF, it is difficult but important to choose the right number of clusters. We show that the widely-used consensus NMF in genomic analysis for choosing the number of clusters have critical flaws and can produce misleading results. We propose a variation of the prediction strength measure arising from statistical inference to evaluate the stability of clusters and select the right number of clusters. Our measure shows promising performances in artificial simulation experiments. Large-scale applications bring substantial efficiency challenges to existing algorithms for computing NMF. An important example is topic modeling where users want to uncover the major themes in a large text collection. Our strategy of accelerating NMF-based clustering is to design algorithms that better suit the computer architecture as well as exploit the computing power of parallel platforms such as the graphic processing units (GPUs). A key observation is that applying rank-2 NMF that partitions a data set into two clusters in a recursive manner is much faster than applying the original NMF to obtain a flat clustering. We take advantage of a special property of rank-2 NMF and design an algorithm that runs faster than existing algorithms due to continuous memory access. Combined with a criterion to stop the recursion, our hierarchical clustering algorithm runs significantly faster and achieves even better clustering quality than existing methods. Another bottleneck of NMF algorithms, which is also a common bottleneck in many other machine learning applications, is to multiply a large sparse data matrix with a tall-and-skinny dense matrix. We use the GPUs to accelerate this routine for sparse matrices with an irregular sparsity structure. Overall, our algorithm shows significant improvement over popular topic modeling methods such as latent Dirichlet allocation, and runs more than 100 times faster on data sets with millions of documents.

APA, Harvard, Vancouver, ISO, and other styles

45

Bulteau, François. "Ciblage in vivo des tumeurs via l'antigène Tn : Développement d'un cluster de Macrophage Galactose Lectine Human Macrophage Galactose-Type Lectin (MGL) Recognizes the Outer Core of Escherichia coli Lipooligosaccharide." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALV048.

Full text

Abstract:

L’ensemble des cellules, qu’elles soient procaryotes ou eucaryotes, est doté d’une couche de glycosylation externe riche et diversifiée, composant la face dominante immédiate en relation à leur environnement. Elles résultent de processus enzymatiques complexes liant les sucres entre eux et sur des protéines ou lipides. Des variations du « glycome » peuvent apparaître dans certaines pathologies. Les cancers sont les pathologies les plus fréquentes présentant des anomalies de ces glycosylations. Ces altérations sont quasi systématiques à la surface des cellules cancéreuses. Parmi celles-ci, l’antigène Thomsen-nouveau (Tn), un N-acétylgalactosamine (GalNAc) sur une sérine ou une thréonine, est fortement exprimé dans 90% des carcinomes mammaires ainsi que dans les cancers de la vessie, du col de l’utérus, de l’ovaire, du colon, de l’estomac et de la prostate. L’omniprésence de l’antigène Tn dans de nombreux cancers, associés à son absence dans les cellules saines, en fait une cible de choix pour la thérapie ciblée ou des vaccins synthétiques antitumoraux. Aucun anticorps ciblant l’antigène Tn n’est à ce jour disponible du fait de la difficulté à développer un anticorps avec une telle spécificité. Ainsi, nous nous sommes intéressés à une autre stratégie de ciblage, basée sur l’utilisation d’une molécule capable de reconnaître l’antigène Tn. Les lectines de type C sont une famille de protéines capables de se lier spécifiquement et de façon réversible à certains glucides, en présence de calcium. La macrophage galactose lectine (MGL) est une lectine de type C ayant une affinité très importante pour le GalNac et ses dérivés comme l’antigène Tn. Ce travail a consisté, dans un premier temps, à l’utilisation d’une forme recombinante soluble de la MGL pour valider le potentiel de cet outil pour le ciblage des cellules cancéreuses. Les différentes expériences, in vitro et in vivo, impliquant la MGL, ont démontré la capacité de cette dernière à cibler spécifiquement les tumeurs humaines via l’antigène Tn. La partie extracellulaire de la MGL est de ce fait un très bon candidat de vecteur pour le diagnostic et l’imagerie de tumeurs humaines et potentiellement pour l’administration de médicaments. Dans un deuxième temps, diverses stratégies de développement d’un outil bifonctionnel exploitant cette lectine ont été exploré. Le but était de créer une plateforme peptidique fonctionnalisable d’une part avec plusieurs domaines lectines, afin de contrôler l’affinité de reconnaissance, et d’autre part des groupements fonctionnels variable selon l’application recherché (diagnostique, thérapeutique, ...). Les différentes stratégies de couplage employées nous ont permis d’accrocher plusieurs CRD de lectine sur un support peptidique, cela en conservant l’état tridimensionnel et fonctionnel des protéines. Les caractérisations effectuées démontrent une importante augmentation de l’affinité directement fonction du nombre de lectine ajouté sur la plateforme. Ce travail ouvre la voie vers de nouveaux systèmes de ciblage des sucres modulable à façon
All cells, whether prokaryotic or eukaryotic, have a rich and diversified external glycosylation layer, forming the immediate dominant face in relation to their environment. They result from complex enzymatic processes linking sugars to each other and to proteins or lipids. Variations of the "glycome" can appear in certain pathologies. Cancers are the most frequent pathologies with abnormalities in these glycosylations. These alterations are almost systematic on the surface of cancer cells. Among them, the Thomsen-new antigen (Tn), an N-acetylgalactosamine (GalNAc) on a serine or threonine, is strongly expressed in 90% of mammary carcinomas as well as in cancers of the bladder, cervix, ovary, colon, stomach and prostate. The ubiquitous presence of the Tn antigen in many cancers, combined with its absence in healthy cells, makes it a target of choice for targeted therapy or synthetic anti-tumor vaccines. No antibody targeting the Tn antigen is currently available because of the difficulty in developing an antibody with such specificity. Thus, we were interested in an alternative targeting strategy, based on the use of a molecule capable of recognizing the Tn antigen. C-Type lectins are a family of proteins capable of specifically and reversibly binding to certain carbohydrates in the presence of calcium. Macrophage galactose lectin (MGL) is a C-type lectin with a high affinity for GalNac and its derivatives such as the Tn antigen. This work consisted, initially, in the use of a soluble recombinant form of MGL to validate the potential of this tool for the targeting of cancer cells. The different experiments, in vitro and in vivo, involving MGL, demonstrated the latter's ability to specifically target human tumors via the Tn antigen. The extracellular portion of MGL is therefore a very good vector candidate for the diagnosis and imaging of human tumors and potentially for drug delivery. In a second step, various strategies for the development of a bifunctional tool exploiting this lectin were explored. The goal was to create a peptide platform that could be functionalized on one hand with several lectin domains, in order to control recognition affinity, and on the other hand with functional groups that could be variable according to the application (diagnostic, therapeutic, ...). The different coupling strategies employed allowed us to attach several lectin CRDs to a peptide support, while preserving the three-dimensional and functional state of the proteins. The characterizations carried out show a significant increase in affinity directly related to the number of lectins added to the platform. This work paves the way to new customizable sugar-targeting systems

APA, Harvard, Vancouver, ISO, and other styles

46

Gray, Michelle Elizabeth. "Towards Understanding the Cell Adhesion Mediated by Non-clustered Non-classical Protocadherins." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1605887233542288.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Gray, Michelle Elizabeth. "Towards Understanding the Cell Adhesion Mediated by Non-clustered Non-classical Protocadherins." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1605887233542288.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Kim, Doo Young. "Statistical Modeling of Carbon Dioxide and Cluster Analysis of Time Dependent Information: Lag Target Time Series Clustering, Multi-Factor Time Series Clustering, and Multi-Level Time Series Clustering." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6277.

Full text

Abstract:

The current study consists of three major parts. Statistical modeling, the connection between statistical modeling and cluster analysis, and proposing new methods to cluster time dependent information. First, we perform a statistical modeling of the Carbon Dioxide (CO2) emission in South Korea in order to identify the attributable variables including interaction effects. One of the hot issues in the earth in 21st century is Global warming which is caused by the marriage between atmospheric temperature and CO2 in the atmosphere. When we confront this global problem, we first need to verify what causes the problem then we can find out how to solve the problem. Thereby, we find and rank the attributable variables and their interactions based on their semipartial correlation and compare our findings with the results from the United States and European Union. This comparison shows that the number one contributing variable in South Korea and the United States is Liquid Fuels while it is the number 8 ranked in EU. This comparison provides the evidence to support regional policies and not global, to control CO2 in an optimal level in our atmosphere. Second, we study regional behavior of the atmospheric CO2 in the United States. Utilizing the longitudinal transitional modeling scheme, we calculate transitional probabilities based on effects from five end-use sectors that produce most of the CO2 in our atmosphere, that is, the commercial sector, electric power sector, industrial sector, residential sector, and the transportation sector. Then, using those transitional probabilities we perform a hierarchical clustering procedure to classify the regions with similar characteristics based on nine US climate regions. This study suggests that our elected officials can proceed to legislate regional policies by end-use sectors in order to maintain the optimal level of the atmospheric CO2 which is required by global consensus. Third, we propose new methods to cluster time dependent information. It is almost impossible to find data that are not time dependent among floods of information that we have nowadays, and it needs not to emphasize the importance of data mining of the time dependent information. The first method we propose is called “Lag Target Time Series Clustering (LTTC)” which identifies actual level of time dependencies among clustering objects. The second method we propose is the “Multi-Factor Time Series Clustering (MFTC)” which allows us to consider the distance in multi-dimensional space by including multiple information at a time. The last method we propose is the “Multi-Level Time Series Clustering (MLTC)” which is especially important when you have short term varying time series responses to cluster. That is, we extract only pure lag effect from LTTC. The new methods that we propose give excellent results when applied to time dependent clustering. Finally, we develop appropriate algorithm driven by the analytical structure of the proposed methods to cluster financial information of the ten business sectors of the N.Y. Stock Exchange. We used in our clustering scheme 497 stocks that constitute the S&P 500 stocks. We illustrated the usefulness of the subject study by structuring diversified financial portfolio.

APA, Harvard, Vancouver, ISO, and other styles

49

Lindvall, Jenny. "Green and red fluorescent protein tagging of endogenous proteins in glioblastoma using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-314151.

Full text

Abstract:

Glioblastoma multiforme is the most malignant primary brain tumor that affects adults, recognized by the World Health Organization as an aggressive grade IV astrocytoma. Patients diagnosed with this type of tumor are left with a poor prognosis even with the most advanced treatment available. The cancer is quite heterogeneous and is typically categorized into four different subtypes depending on genetic aberrations and patient characteristics. Furthermore, researchers have discovered a subpopulation of glioblastoma cells, known as cancer stem cells, which are thought to be resistant to current therapies and responsible for tumor reoccurrence and relapse. Previous studies, in addition to this one, have found that the differentiation of glioblastoma cells downregulate nestin protein expression, the selected stem cell marker, and upregulate glial fibrillary acid protein expression, the selected differentiation marker, using immunofluorescence. Thus, one alternative treatment option is to understand the mechanism underlying the differentiation of cancer stem cells. Four cell cultures representative of each glioblastoma subtype will be endogenously tagged using the genome editing system, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9). The representative stem cell marker, nestin, will be tagged with a green fluorescent protein, while the chosen differentiation marker, glial fibrillary acid protein, will be tagged with a red fluorescent protein. Several drugs were screened to analyze whether the drugs had a differentiation effect on the glioblastoma cells. As a result, strong evidence indicated that bone morphogenetic protein four upregulated glial fibrillary acid protein expression levels to the same extent as the differentiation control media using 5% fetal bovine serum. The goal of this study is to establish a method to directly monitor the differentiation process of glioblastoma cells as a novel molecular screening method. In this case, all glioblastoma cells, even the ones resistant to treatment, can be eliminated through an initial “pre-treatment” by forcing differentiation of cancer stem cells, making the cells more susceptible to the chemotherapy drugs. In the long run, glioblastoma patients would have a chance at a more positive prognosis; a longer life that is free of glioblastoma.
Master Thesis in Applied Biotechnology

APA, Harvard, Vancouver, ISO, and other styles

50

Valdeolivas, Urbelz Alberto. "Approaches to explore multiplex biological networks and application to study premature aging diseases." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0106.

Full text

Abstract:

Les gènes et les protéines n’agissent pas de manière isolée dans les cellules, mais interagissent plutôt pour faire leurs fonctions dans les processus biologiques. Ces interactions peuvent être représentées sous forme de grands réseaux dans lesquels les nœuds sont des gènes ou des protéines et les arêtes représentent leurs interactions. Diverses approches basées sur la théorie des graphes ont été développées pour extraire la connaissance fonctionnelle contenue dans ces réseaux. Néanmoins, ces méthodes ont été principalement appliquées à des réseaux individuels, en ignorant la diversité des interactions biologiques. Nous déclarons que ces différents types d’interactions peuvent être représentés sous la forme de réseaux multiplexes, c’est-à-dire des ensembles de réseaux partageant les mêmes nœuds, ce qui permet une description plus précise des systèmes biologiques. Cette thèse est focalisée sur le développement de nouveaux algorithmes étendant aux réseaux multiplexes certaines méthodes populaires de la théorie des graphes en biologie computationnelle, ainsi que sur leur application à l’étude des maladies humaines. Du côté des applications, nous nous concentrons sur les maladies liées au vieillissement prématuré, un groupe de maladies génétiques ressemblant à certains aspects du vieillissement physiologique à un âge précoce. Nous avons appliqué nos algorithmes pour détecter les modules associés à plus de 70 syndromes annotés avec un phénotype lié au vieillissement prématuré. Les résultats ont révélé le paysage des processus moléculaires perturbés dans ces maladies, qui peuvent être mis en parallèle avec les caractéristiques du vieillissement physiologique
Genes and proteins do not act isolated in cells but rather interact to perform their functions in signaling pathways, molecular complexes, or, more generally, biological processes. These interactions can be represented as large networks in which nodes are genes or proteins and edges represent their interactions. Various graph-theory based approaches have been developed to extract the functional knowledge contained in biological networks. Nevertheless, these methods have been mainly applied to individual networks, ignoring the diversity of biological interactions. We state here that these different types of interactions can be represented as multiplex networks, i.e. collections of networks sharing the same nodes, leading to a more accurate description of biological systems. This thesis focuses on the extension from individual to multiplex networks of some of the state-of-the-art guilt-by-association methods in computational biology, and on their application to the study of human diseases. On the application side, we concentrate on premature aging diseases, a group of rare genetic disorders that resemble some aspects of physiological aging at an early age. In this framework, we applied our algorithms to detect the modules associated to more than 70 disorders annotated with at least one premature aging related phenotype. The results revealed the landscape of perturbed molecular processes in premature aging diseases, which can be paralleled with the hallmarks of physiological aging to help identifying common and specific features

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Cancer Clusters'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles