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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.
1

Biomarker mRNAs for staging and prognosis of colorectal cancer

Ohlsson, Lina January 2011 (has links)
Mesenteric lymph node (ln) metastasis is the single most important prognostic characteristic in colorectal cancer (CRC). The ln status is used for staging and is a decisive selection criterion for postoperative adjuvant therapy. However, it is difficult to accurately determine ln status by routine histopathology (H&E). Thus, ~25% of CRC patients, who by H&E are considered to lack tumor cells in their lns, i.e. stage I+II, die from CRC. To explore the utility of biomarker mRNA analysis for staging and prognosis of CRC, lns were collected at surgery and mRNA levels for fourteen biomarkers, including carcinoembryonic antigen (CEA), kallikrein 6 (KLK6), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CEACAM1-S, CEACAM6 and mucin 2 (MUC2), were determined by quantitative RT-PCR with RNA copy standards. Results were compared to routine H&E analysis. The biomarkers were analyzed for capacity to detect disseminated tumor cells in lns. mRNA levels were determined in CRC- and control lns, primary tumor, normal colon, immune cells and fibroblasts. Lack of expression in immune cells and fibroblasts and high and homogenous expression in primary tumors showed to be the determining factors. CEA fulfilled these criteria best, followed by KLK6, CK20, GCC, and MUC2. Utility of the biomarker mRNAs for staging and prognosis was examined in 174 CRC patients. CEA was the best predictor of disease-free survival time after surgery with a 71 months difference between CEA(+) and CEA(-) patients and a hazard ratio of 5.1 for risk of recurrence for CEA(+) patients. CEA, CK20 and MUC2 were more sensitive than H&E in that these biomarkers identified patients who succumbed from recurrent CRC although H&E analysis had failed to detect the disseminated tumor cells. Combined analysis of CEA and MUC2 mRNAs improved prediction of outcome. Patients with high risk for recurrence had low MUC2/CEA ratios. KLK6 mRNA was identified as a potential progression marker by genome-wide microarray analysis of gene expression. It was found to be ectopically expressed in CRC tumor cells. KLK6(+) lns was an indicator of poor prognosis (hazard ratio 3.7). Notably, the actual level was of importance for outcome. The higher the KLK6 mRNA levels the greater the risk of recurrence. At the 90 thpercentile the hazard risk ratio for KLK6(+) patients was 5.6. KLK6 positivity in lns with low numbers of tumor cells, as indicated by low CEA mRNA levels, indicated poor prognosis (hazard ratio 2.8). Thus, KLK6 adds prognostic information to CEA analysis. Increased levels of mRNA for the proinflammatory cytokine interferon- and the down-regulatory cytokine interleukin-10 in lns of CRC patients suggested ongoing immune reactions against the infiltrating tumor cells. Elevated TGF-1 levels correlated weakly with survival, suggesting protection by the antiproliferative effect of TGF-1 in sporadic cases. CEA mRNA was the best single biomarker for staging and prediction of disease-free survival time and risk of recurrence after surgery. In addition to CEA, KLK6 positivity and low MUC2/CEA ratio correlate with poor prognosis. Thus, CEA, MUC2 and KLK6 mRNAs form a strong "trio" for staging and prediction of outcome for CRC patients.
2

The Effect of Patient Race upon Physicians' Colorectal Cancer Screening: A Retrospective Medical Record Review and Physician Pattern Variable Analysis

Borum, Marie L. 22 May 2003 (has links)
Degree awarded (2003): EdDHRD, Counseling, Human and Organizational Studies, George Washington University / ABSTRACT OF DISSERTATION<p>The Effect of Patient Race upon Physicians Colorectal Cancer Screening: A Retrospective Medical Record Review and Physician Pattern Variable Analysis<p>There is a significant disparity in the health status of African-Americans and whites in the United States. Studies have revealed that African-Americans have higher mortality rates from colorectal cancer than whites. Differences in colorectal cancer screening of African-Americans compared to whites may account for a proportion of the excess mortality. This study evaluated internal medicine resident physicians colorectal cancer screening practices in African-American and white patients. Additionally, an analysis of physicians pattern variable orientation was performed to determine if there was a relationship between physicians orientation and adherence to colorectal cancer screening guidelines.<p>A retrospective review of medical records from January 2002 through March 2002 was conducted to assess internal medicine resident physicians performance of colorectal cancer screening. Univariate analysis revealed that there were statistically significant differences in the rate at which physicians performed rectal examinations (p=0.0039), fecal occult blood testing (p=0.0006) and colonic examinations (p<0.0001) in African-American compared to white patients. Multivariate analysis, evaluating patient race, patient gender, patient age and physician gender, demonstrated that patient race was the only factor significant for not performing colorectal cancer screening tests.<p>Physicians perspectives about the medical profession and the delivery of medical services were assessed by evaluating pattern variable orientations. Integrative, value and motivational orientations of the physicians were determined by using semi-structured interviews. All of the physicians had a self-orientation (integrative pattern variable), a universalistic-achievement orientation (value pattern variables) and a specificity orientation (motivational pattern variable). However, the physicians differed in their affectivity-affective neutrality orientation (motivational pattern variable). All of the physicians who had an affective orientation toward their patients adhered to colorectal cancer screening recommendations. The physicians who expressed affective neutrality toward their patients did not adhere to colorectal cancer screening recommendations.<p>This study revealed significant differences in the performance of colorectal cancer screening in African-American compared to white patients. Additionally, physicians pattern variable orientations correlated with adherence to practice guidelines. This study is important because it provides information about physician practice patterns. The results of this study can serve as the basis for the development of educational interventions for physicians that can improve health care delivery. / Advisory Committee: Dr. John Williams, Dr. David Schwandt (Chair), Dr. Andrea Casey, Dr. Jeffrey Lenn, Dr. Victor Scott
3

A bioinformatics meta-analysis of differentially expressed genes in colorectal cancer

Chan, Simon Kit 05 1900 (has links)
BACKGROUND: Elucidation of candidate colorectal cancer biomarkers often begins by comparing the expression profiles of cancerous and normal tissue by performing high throughput gene expression profiling. While many such studies have been performed, the resulting lists of differentially expressed genes tend to be inconsistent with each other, suggesting that there are some false positives and negatives. One logical solution to this problem is to determine the intersection of the lists of differentially expressed genes from independent studies. It is expected that genes that are biologically relevant to cancer tumorigenesis will be reported most often, while sporadically reported genes are due to the inherent biases and limitations of each of the profiling platforms used. However, the statistical significance of the observed intersection among many independent studies is usually not considered. PURPOSE: To address these issues, we developed a computational meta-analysis method that ranked differentially expressed genes based on the following criteria, which are presented in order of importance: the amount of intersection among studies, total tissue sample sizes, and average fold change in expression. We applied this meta-analysis method to 25 independent colorectal cancer profiling studies that compared cancer versus normal, adenoma versus normal, and cancer versus adenoma tissues. RESULTS: We observed that some genes were consistently reported as differentially expressed with a statistically significant frequency (P <.0001) in the cancer versus normal and adenoma versus normal comparisons, but not in the cancer versus adenoma comparison. We performed a review of some of the high ranking candidates and determined that some have previously been shown to have diagnostic and/or prognostic utility in colorectal cancer. More interestingly, the meta-analysis method also identified genes that had yet to be tested and validated as biomarkers. Thus, these candidates are currently being validated at the protein level on colorectal tissue microarrays. CONCLUSION: Our meta-analysis method identified genes that were consistently reported as differentially expressed. Besides identifying new biomarker candidates, our meta-analysis method also provides another filter to remove false positive genes from further consideration. In conclusion, the genes presented here will aid in the identification of highly sensitive and specific biomarkers in colorectal cancer.
4

A bioinformatics meta-analysis of differentially expressed genes in colorectal cancer

Chan, Simon Kit 05 1900 (has links)
BACKGROUND: Elucidation of candidate colorectal cancer biomarkers often begins by comparing the expression profiles of cancerous and normal tissue by performing high throughput gene expression profiling. While many such studies have been performed, the resulting lists of differentially expressed genes tend to be inconsistent with each other, suggesting that there are some false positives and negatives. One logical solution to this problem is to determine the intersection of the lists of differentially expressed genes from independent studies. It is expected that genes that are biologically relevant to cancer tumorigenesis will be reported most often, while sporadically reported genes are due to the inherent biases and limitations of each of the profiling platforms used. However, the statistical significance of the observed intersection among many independent studies is usually not considered. PURPOSE: To address these issues, we developed a computational meta-analysis method that ranked differentially expressed genes based on the following criteria, which are presented in order of importance: the amount of intersection among studies, total tissue sample sizes, and average fold change in expression. We applied this meta-analysis method to 25 independent colorectal cancer profiling studies that compared cancer versus normal, adenoma versus normal, and cancer versus adenoma tissues. RESULTS: We observed that some genes were consistently reported as differentially expressed with a statistically significant frequency (P <.0001) in the cancer versus normal and adenoma versus normal comparisons, but not in the cancer versus adenoma comparison. We performed a review of some of the high ranking candidates and determined that some have previously been shown to have diagnostic and/or prognostic utility in colorectal cancer. More interestingly, the meta-analysis method also identified genes that had yet to be tested and validated as biomarkers. Thus, these candidates are currently being validated at the protein level on colorectal tissue microarrays. CONCLUSION: Our meta-analysis method identified genes that were consistently reported as differentially expressed. Besides identifying new biomarker candidates, our meta-analysis method also provides another filter to remove false positive genes from further consideration. In conclusion, the genes presented here will aid in the identification of highly sensitive and specific biomarkers in colorectal cancer.
5

Alterations in adipose tissue in colorectal cancer patients

Ebadi, Maryam Unknown Date
No description available.
6

Does geography influence the treatment and outcomes of colorectal cancer in the province of Manitoba?

Helewa, Ramzi M. 09 August 2012 (has links)
Background: Colorectal cancer (CRC) is the third most common cancer in Manitoba. We sought to determine if regional differences exist for treatments, wait times, and quality measures for Manitobans with CRC. Methods: A population-based historical cohort analysis for patients diagnosed with CRC between 2004 and 2006 was undertaken using administrative databases. Results: 2086 patients were diagnosed with Stage I-IV CRC between 2004 and 2006. Diagnosis wait times and treatment wait times were longer in Winnipeg than rural Manitoba. There were no differences between Winnipeg and rural Manitoba in rates of total colonic examination, adequate lymphadenectomy, and consultations with oncologists. Rural patients with rectal cancer experienced higher local recurrence and mortality rates than urban patients. Conclusion: This study establishes population-based benchmarks for the quality of CRC therapy in Manitoba. Minimal geographic differences exist for quality measures. For rectal cancer local recurrence, rural patients represent an important area for quality improvement initiatives.
7

Does geography influence the treatment and outcomes of colorectal cancer in the province of Manitoba?

Helewa, Ramzi M. 09 August 2012 (has links)
Background: Colorectal cancer (CRC) is the third most common cancer in Manitoba. We sought to determine if regional differences exist for treatments, wait times, and quality measures for Manitobans with CRC. Methods: A population-based historical cohort analysis for patients diagnosed with CRC between 2004 and 2006 was undertaken using administrative databases. Results: 2086 patients were diagnosed with Stage I-IV CRC between 2004 and 2006. Diagnosis wait times and treatment wait times were longer in Winnipeg than rural Manitoba. There were no differences between Winnipeg and rural Manitoba in rates of total colonic examination, adequate lymphadenectomy, and consultations with oncologists. Rural patients with rectal cancer experienced higher local recurrence and mortality rates than urban patients. Conclusion: This study establishes population-based benchmarks for the quality of CRC therapy in Manitoba. Minimal geographic differences exist for quality measures. For rectal cancer local recurrence, rural patients represent an important area for quality improvement initiatives.
8

Expression and regulation of the human colonic butyrate transporter, MCT1, during the transition from normality to malignancy

Lambert, Daniel William January 2002 (has links)
No description available.
9

A histochemical marker of in vivo somatic mutation within the human colon

Campbell, Fiona January 1995 (has links)
No description available.
10

Modulation of the immune response to surgical trauma and malignancy with recombinant interleukin-2

Deehan, David J. January 1996 (has links)
This thesis evaluated the role of rIL-2 in patients with advanced colorectal cancer and also, as a perioperative regime, in patients with localized colorectal cancer undergoing surgical resection. Twenty patients with advanced colorectal cancer received up to six cycles of chemoimmunotherapy, each consisting of 5-fluorouracil, levamisole and rIL-2 at 18x10<SUP>6</SUP>IU/m<SUP>2</SUP>/24 for 120 hours. Responding patients were found to have significantly lower pre-treatment serum IL-6 and soluble IL-2 receptor levels, compared with non-responders. Differential patterns of host cytokine release were also identified. Haemodynamic monitoring found that indices of rIL-2-mediated toxicity, e.g. weight gain correlated with alterations in serum cytokine concentrations. In a separate study, eighteen patients, undergoing curative surgery for localized colorectal cancer, were randomized to receive placebo or bolus low-dose subcutaneous rIL-2 for three days preoperatively. rIL-2 was found to significantly enhance host antitumour natural cytotoxicity, monocyte activity and immune cell surface activation marker expression (e.g. CD25). Circulating levels of key host cytokines (e.g. interleukin-6, soluble interleukin-2 receptor) were elevated in the immediate postoperative period in these patients. Mesenteric release of key cytokines was determined in patients undergoing resection for benign and malignant colorectal disease through portal sampling at surgery. Higher patterns of release were found in patients with malignancy suggesting local modulation of immune activity. rIL-2 has been found to beneficially enhance host immune reactivity in patients with localized and advanced colorectal cancer. The nephrotoxic potential of rIL-2 therapy was determined through urinary enzyme release, plasma renin and standard blood biochemistry measurements. RIL-2, when administered carefully, may form the basis of further adjuvant immunotherapy in both the peri-operative period and in patients with advanced colorectal cancer.

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