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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

Biological markers demonstrate utility and predictive value in inflammatory bowel disease

2015 December 1900 (has links)
Biological markers (“biomarkers”) may have applications in inflammatory bowel disease (IBD), a chronic disease of the gastrointestinal tract. Clinicians are presented with several challenges when treating IBD. Instead of performing expensive and invasive endoscopic procedures - if even possible, as resources for these procedures can be limited - biomarkers could be used to diagnose, assess disease activity and prognosis, and guide medical therapy, particularly in situations where novel biologics are involved. At this time, the use of biomarkers is limited, since few have been useful in predicting disease severity, prognosis and therapeutic response in IBD. Previous research cohorts studying biomarkers are limited due to varying heterogeneity between subjects that confounds the results since patients have variable disease courses. The main aim of this work was to evaluate the utility of biomarkers in IBD. To do this, biomarkers were included into a composite score with other patient reported outcomes (PRO) to predict endoscopic disease activity. Next, we examined the role of biomarkers in newly diagnosed IBD. Lastly, fecal calprotectin (FC) was evaluated in healthy pregnant and IBD patients, establishing reference values and practicality in this clinical group. We also studied the relationship between biomarkers and environmental factors, such as fecal microbiota. We hypothesized biomarker concentration would be elevated with increased clinical and endoscopic measures, and predictive of response to medical therapy in newly diagnosed patients. Additionally, we theorized the inclusion of biomarkers into composite scores would outperform existing scoring models in predicting endoscopic severity. Furthermore, FC levels would be below the limit of detection in healthy pregnancy and elevated in IBD pregnancy. The inclusion of biomarkers into composite scoring models outperformed existing clinical scores. In newly diagnosed patients, modest relationships were found between biomarkers and clinical and endoscopic markers of disease. Lastly, the presence of FC was elevated in pregnant IBD and not significant in healthy pregnancy; thus, FC is useful in IBD and pregnancy. Our work confirmed the significance of biomarkers in several clinical areas of IBD, along with the issues presented in recruiting newly diagnosed patients in small research centres. Future work will incorporate biomarkers into medical triage and as an endpoint in nutritional interventions.

Magnetic Resonance Imaging Biomarkers For Targeted Cancer Therapies

Stephen, Renu M. January 2008 (has links)
In 2007, there will be an estimated 178,480 new cases of breast cancer diagnosed in women in the United States. The elucidation of the vast heterogeneity of individual tumors has led to a paradigm shift from a one-size fits all treatment strategy to more individualized treatment based on the molecular profile of the tumor. Identifying biomarkers that respond to or predict the action of drugs is important in identifying efficacious targets and drugs that will improve clinical outcome. To examine this, we first identified two breast cancer cell lines (ACC-3199 and ACC-3171) from a panel of low passage breast cells lines that were capable of growing serially as tumor xenografts. This was followed by the in vivo molecular characterization of these two cell lines. In ACC-3199 tumors, we identified a gain of pAKT expression compared to cultured cells. Based on this finding, we investigated the role of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as potential imaging biomarkers in identifying early response to PX-866, a PI3K inhibitor, in ACC-3199 tumors as represented by changes in tumor cellularity and hemodynamic parameters, respectively. Our results indicated that DW-MRI was able to identify an early response to PX-886 in ACC-3199 tumors as defined by an increase in the apparent diffusion coefficient (ADC) value of the tumors prior to changes in tumor volumes. Using DCE-MRI, we were able to conclude that PX-866 was not an effective anti-angiogenic agent as indicated by an increase in tumor permeability following therapy. Based on the VEGFR2 expression observed in ACC-3171 tumor xenografts, we examined the response of MDA-MB-231/GFP and ACC-3171 tumor xenografts to the anti-angiogenic agent, sunitinib, using the same imaging modalities. DW-MRI was able to detect increases in ADC values as early as 12 h post-treatment in both MDA-MB-231/GFP and ACC-3171 tumors. Thus, it appears that DW-MRI may be a useful clinical test in predicting the early response to PI3K and anti-angiogenic inhibitors. These imaging approaches, in addition to the further molecular characterization of breast tumors may lead to the improvement and development of medical therapies for breast cancer patients.

Markers of synovial inflammation in cohorts at risk of knee osteoarthritis

Kluzek, Stefan January 2016 (has links)
<b>Background and objectives.</b> Knee osteoarthritis (KOA) is a leading cause of disability in the developed world. Additionally, it is possibly linked with premature mortality. Low-grade inflammation is associated with a high risk of non-traumatic KOA incidence but also with metabolic syndrome. Knee injury is a major risk factor for KOA and is associated with an inflammatory response. Heterogeneity of both the symptoms and progression makes early identification of individuals at risk difficult. The aim of this thesis was to examine the diagnostic value of selected biomarkers to identify microscopic synovitis, examine their predictive value for KOA development and any association with excess premature mortality. <b>Methods.</b> Four serum biomarkers, COMP, resistin, C3M and CRPM, all linked with both knee pain and synovial or systemic inflammation, were selected and an additional sonographic marker was tested. Data from two cohorts has been utilised for the purpose of this thesis: the Oxford Knee Injury Cohort, a prospective study of NHS patients with recent ACL and/or meniscal injuries, and the Chingford women's study, a community-based prospective cohort with over 23 years of follow-up. <b>Results.</b> Cross-sectionally, sonographic markers correspond well with microscopically defined post-traumatic synovitis. Two biomarkers, COMP and resistin, were associated with development of incident radiographic KOA (RKOA), while two others, C3M and CRPM, predicted development of painful RKOA independently to age and BMI. High C3M levels and presence of painful RKOA were associated with premature mortality. Knee pain alone, especially in presence of RKOA was an independent predictor of mortality, but RKOA without pain was not. <b>Conclusion.</b> These results support the use of the studied biomarkers in complex predictive models for development of KOA and associated premature mortality. Taking the competing risk of death into account is an important consideration in this field.

Circulating tumor markers in extranodal lymphomas. / CUHK electronic theses & dissertations collection

January 2002 (has links)
Lei Ieng Kit Kenny. / "April 2002." / Thesis (M.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 89-118). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Conditional Differential Expression for Biomarker Discovery In High-throughput Cancer Data

Wang, Dao Sen 15 February 2019 (has links)
Biomarkers have important clinical uses as diagnostic, prognostic, and predictive tools for cancer therapy. However, translation from biomarkers claimed in literature to clinical use has been traditionally poor. Importantly, clinical covariates have been shown to be important factors in biomarker discovery in small-scale studies. Yet, traditional differential gene expression analysis for expression biomarkers ignores covariates, which are only accounted for later, if at all. We conjecture that covariate-sensitive biomarker identification should lead to the discovery of more robust and true biomarkers as confounding effects are considered. Here we examine gene expression in more than 750 breast invasive ductal carcinoma cases from The Cancer Genome Atlas (TCGA-BRCA) in the form of RNA-Seq data. Specifically, we focus on differential gene expression with respect to understanding HER2, ER, and PR biology – the three key receptors in breast cancer. We explore methods of differential expression analysis, including non-parametric Mann-Whitney-Wilcoxon analysis, generalized linear models with covariates, and a novel categorical method for covariates. We tested the influence of common patient characteristics, such as age and race, and clinical covariates such as HER2, ER, and PR receptor statuses. More importantly, we show that inclusion of a correlated covariate (e.g. PR status as a covariate in ER analysis) substantially changes the list of differentially expressed genes, removing many likely false positives and revealing genes obscured by the covariate. Incorporation of relevant covariates in differential gene expression analysis holds strong biological importance with respect to biomarker discovery and may be the next step towards better translation of biomarkers to clinical use.

Assessing dynamic micromechanical markers for the evaluation of the prostate for cancer

Good, Daniel William January 2016 (has links)
The diagnostic pathway for prostate cancer involves the blood test prostate specific antigen (PSA) which has high sensitivity but low specificity at age related reference ranges. The resultant clinical consequence is a large number of negative diagnostic studies (transrectal ultrasound guided biopsies - TRUS). There is a need for a secondary screening test to help improve on the current diagnostic pathway. Mechanical markers have been used previously to assess the prostate for disease with numerous ex-vivo reports of differences between benign and malignant prostates. There have been no in-vivo studies with direct elasticity assessment devices for prostate cancer detection. This thesis forms part of work in a collaborative study in conjunction with engineers who have created a microscale device, capable of dynamic elasticity assessment. The specific objectives of this thesis were to a) assess dynamic micromechanical markers for the detection and differentiation of clinically significant from insignificant prostate cancer b) to identify relationships between mechanical and histopathological variables in the ex-vivo and in-vivo environments and c) assess the potential for these markers to differentiate peri-prostatic tissues. A prospective study was set-up with full ethics and management approvals with patients undergoing a systematic mechanical assessment of their prostate using the E-finger device and after prostate excision a systematic ex-vivo mechanical assessment on a calibrated stage. The ex-vivo assessment allowed accurate histopathological and mechanical variable assessment in a controlled environment. 7-Tesla ex-vivo MRI scanning aided in assessing the limitations of mechanical assessment of the prostate. There were clear consistent differences between individual dynamic micromechanical markers for benign and tumour containing measurement areas in both environments. Modelling of these dynamic micromechanical markers yielded encouraging accuracy levels for the detection of prostate cancer and differentiation of significant from insignificant disease. There were associations between individual mechanical markers and important histopathological features associated with cancer (acinar size, tumour volume and reactive stroma). These markers showed promise and utility in the differentiation of prostate from bladder and rhabdosphincter. This work demonstrates the clear potential translational uses for dynamic micromechanical markers in the assessment of the prostate for cancer.

Hypertension : Experimental and clinical pharmacological studies

Leary, William, Peregrine, Pepperrell 08 September 1985 (has links)
A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Science (Medicine). / The publications forming this submission cover two broad fields. A series of papers deal with experimental hypertension ; possible roles for angiotensin and prostanoid substances in the pathogenesis of hypertension were investigated. The results indicated that the capacity of kidney to inactivate angiotensin II could be quite profoundly altered by inducing hypertension using the one and two-clip Goldblatt methods or by altering the sodium chloride content of the diet. / IT2018

Novel nanoarchitectures for electrochemical biosensing

Archibald, Michelle M. January 2016 (has links)
Thesis advisor: Thomas C. Chiles / Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point-of-care (POC) technologies. Current methods, while sensitive, do not adequately allow for POC applications due to several limitations, including complex instrumentation, high reagent consumption, and cost. We have investigated two novel nanoarchitectures, the nanocoax and the nanodendrite, as electrochemical biosensors towards the POC detection of infectious disease biomarkers to overcome these limitations. The nanocoax architecture is composed of vertically-oriented, nanoscale coaxial electrodes, with coax cores and shields serving as integrated working and counter electrodes, respectively. The dendritic structure consists of metallic nanocrystals extending from the working electrode, increasing sensor surface area. Nanocoaxial- and nanodendritic-based electrochemical sensors were fabricated and developed for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). Both nanoarchitectures exhibited levels of sensitivity that are comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, these electrochemical nanosensors provide a simple electrochemical readout and a miniaturized platform with multiplexing capabilities toward POC implementation. Further development as suggested in this thesis may lead to increases in sensitivity, enhancing the attractiveness of the architectures for future POC devices. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.


Unknown Date (has links)
This study examined the acute and chronic responses of brain-derived neurotrophic factor (BDNF), cathepsin B (CatB), insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) and if changes in these biomarkers were correlated during resistance training. Fourteen resistance trained men performed resistance training 3 days per week for 6 weeks in two groups. The only difference between groups was the proximity to failure of each set (4-6 repetitions in reserve or 1-3 repetitions in reserve). Serum was collected immediately before and after training on day 1 of weeks 1 and 6. There were no significant group interactions for any of the biomarkers assessed, there were no main effects for time (p>0.05), and no significant correlations were observed between any of the biomarkers. However, a significant main effect for exercise for BDNF (p=0.03) and IL-6 (p=0.003) was observed. For CatB, a significant exercise × time (p=0.002) interaction was observed, indicating differences in the acute change of CatB in week 6 (+15.78%; g=0.25) vs. week 1 (-7.46%; g=0.13). In summary, these results suggest that multi-joint resistance exercise far from failure can confer a BDNF response. This investigation is the first to demonstrate the potential for acute resistance exercise to elicit a transient increase in CatB. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

Intron Retention Induced Neoantigen as Biomarkers in Diseases

Dong, Chuanpeng 08 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Alternative splicing is a regulatory mechanism that generates multiple mRNA transcripts from a single gene, allowing significant expansion in proteome diversity. Disruption of splicing mechanisms has a large impact on the transcriptome and is a significant driver of complex diseases by producing condition-specific transcripts. Recent studies have reported that mis-spliced RNA transcripts can be another major source of neoantigens directly associated with immune responses. Particularly, aberrant peptides derived from unspliced introns can be presented by the major histocompatibility complex (MHC) class I molecules on the cell surface and elicit immunogenicity. In this dissertation, we first developed an integrated computational pipeline for identifying IR-induced neoantigens (IR-neoAg) from RNA sequencing (RNA-Seq) data. Our workflow also included a random forest classifier for prioritizing the neoepitopes with the highest likelihood to induce a T cell response. Second, we analyzed IR neoantigen using RNA-Seq data for multiple myeloma patients from the MMRF study. Our results suggested that the IR-neoAg load could serve as a prognosis biomarker, and immunosuppression in the myeloma microenvironment might offset the increasing neoantigen load effect. Thirdly, we demonstrated that high IR-neoAg predicts better overall survival in TCGA pancreatic cancer patients. Moreover, our results indicated the IR-neoAg load might be useful in identifying pancreatic cancer patients who might benefit from immune checkpoint blockade (ICB) therapy. Finally, we explored the association of IR-induced neo-peptides with neurodegeneration disease pathology and susceptibility. In conclusion, we presented a state-of-art computational solution for identifying IR-neoAgs, which might aid neoantigen-based vaccine development and the prediction of patient immunotherapy responses. Our studies provide remarkable insights into the roles of alternative splicing in complex diseases by directly mediating immune responses. / 2023-08-16

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