Indiana University-Purdue University Indianapolis (IUPUI) / The occurrence of colorectal cancer among those over the age of 50 is decreasing; conversely, the rate of diagnosis for those under 50 years old is increasing. While medical researchers scramble to identify the cause for this increase, young onset colorectal cancer (YOCC) patients and survivors are left to navigate a new normal. This new normal often includes awkward and troublesome concerns such as scarring, colostomy bags, and bowel problems. Contrary to those diagnosed with colorectal cancer later in life, those that are diagnosed at a younger age are forced to deal with these issues for many years. The purpose of this exploratory study was to identify privacy issues surrounding YOCC. Because of the significant increase in diagnoses, YOCC is now being researched independently from colorectal cancer in general. The topic of privacy has been researched in academic disciplines, including medicine. Privacy issues surrounding cancer have been researched, as well. Yet, the topic of privacy concerns facing YOCC patients/survivors has been overlooked. It is important to identify privacy concerns specific to YOCC patients/survivors as the information could help health care providers, communication scholars, and caregivers. Patient narratives were analyzed employing thematic analysis to identify privacy concerns of YOCC patients/survivors through the lens of Communication Privacy Management theory (CPM theory). Results indicated that participants discussed disclosure of their YOCC journey as a process. Within this disclosure process, YOCC patients/survivors identified specific privacy issues that influenced the way they disclosed or concealed information specific to their illness. There is a growing need for more research into the YOCC community due to the increase in diagnosis rates and their unique privacy concerns. Potential topics for future research include the impact of COVID-19, patient desire to help others, social media influence on disclosure, how patient disclosure could impact provider training, dating with YOCC, and specific demographic research.

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第23758号 / 医博第4804号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 今中 雄一, 教授 川上 浩司, 教授 小濱 和貴 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23799号 / 医博第4845号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妹尾 浩, 教授 中川 一路, 教授 伊藤 貴浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23797号 / 医博第4843号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 藤田 恭之, 教授 小濱 和貴 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background Reported outcomes for colorectal cancer associated with Inflammatory Bowel Disease are inconsistent. We compared survival outcomes in colorectal cancer patients with and without Inflammatory Bowel Disease using a population-based cohort and elicited prognostic factors associated with survival Methods Adult patients with a diagnosis of colorectal cancer in 2007-2015 were identified from the Ontario Cancer Registry. Those with Inflammatory Bowel Disease were detected via the validated Ontario Crohn’s and Colitis Cohort. Primary outcome measure was overall survival from time of colorectal cancer diagnosis until the date of death. Secondary outcome measures included treatments received and publicly-provided health care costs. Results Colorectal cancer was diagnosed in 67,137 with Inflammatory Bowel Disease present in 783 (1.2%). The Inflammatory Bowel Disease-associated colorectal cancer patients were younger at diagnosis (median range 55-59 vs 70-74, p<0.001). Five-year survival in Inflammatory Bowel Disease-associated patients was 56.4% (95% CI 52.6-59.9) and 57.0% (95% CI 56.6-57.4) in sporadic colorectal cancer (p=0.8). Inflammatory Bowel Disease was a significant predictor of death (Hazard Ratio=1.45, 95% CI 1.29-1.63, p<0.001) after adjusting for other variables. In patients under 50, 5-year survival was significantly (p<0.001) reduced in the Inflammatory Bowel Disease population (56.8%, 95% CI 49.4-63.5) compared with the sporadic colorectal cancer population (71.4%, 95% CI 70.0-72.7). Similar results were observed in those 50-64 years old. Conclusion Young patients (<65) with Inflammatory Bowel Disease-associated colorectal cancer have worse survival outcomes than young (<65) patients with sporadic colorectal cancer. These findings inform prognostication and may direct future research for this high-risk population. / Thesis / Master of Science (MSc) / Background Reported outcomes for colorectal cancer associated with Inflammatory Bowel Disease are inconsistent. We compared survival outcomes in colorectal cancer patients with and without Inflammatory Bowel Disease using a population-based cohort and elicited prognostic factors associated with survival Methods Adult patients with a diagnosis of colorectal cancer in 2007-2015 were identified from the Ontario Cancer Registry. Those with Inflammatory Bowel Disease were detected via the validated Ontario Crohn’s and Colitis Cohort. Primary outcome measure was overall survival from time of colorectal cancer diagnosis until the date of death. Secondary outcome measures included treatments received and publicly-provided health care costs. Results Colorectal cancer was diagnosed in 67,137 with Inflammatory Bowel Disease present in 783 (1.2%). The Inflammatory Bowel Disease-associated colorectal cancer patients were younger at diagnosis (median range 55-59 vs 70-74, p<0.001). Five-year survival in Inflammatory Bowel Disease-associated patients was 56.4% (95% CI 52.6-59.9) and 57.0% (95% CI 56.6-57.4) in sporadic colorectal cancer (p=0.8). Inflammatory Bowel Disease was a significant predictor of death (Hazard Ratio=1.45, 95% CI 1.29-1.63, p<0.001) after adjusting for other variables. In patients under 50, 5-year survival was significantly (p<0.001) reduced in the Inflammatory Bowel Disease population (56.8%, 95% CI 49.4-63.5) compared with the sporadic colorectal cancer population (71.4%, 95% CI 70.0-72.7). Similar results were observed in those 50-64 years old. Conclusion Young patients (<65) with Inflammatory Bowel Disease-associated colorectal cancer have worse survival outcomes than young (<65) patients with sporadic colorectal cancer. These findings inform prognostication and may direct future research for this high-risk population.

The need for a non-invasive, accurate, easy-to-use, and cost-effective colorectal cancer (CRC) detection device is apparent in the low survival rates seen in late-stage diagnoses. Once CRC has progressed past stage I, the 5-year survival rate drops significantly, and treatment options become less favourable. The best way to treat CRC is to catch it early. The development of an RNA-cleaving fluorogenic DNAzyme (RFD) holds the potential to remediate this deficiency. A DNAzyme, called RFD-FN1, was identified from a synthetic random-sequence DNA library to selectively bind to an unknown target associated with Fusobacterium nucleatum, which has been found to be overabundant in pre- and cancerous colorectal tissue and stool. Target recognition by the DNAzyme induces the cleavage of a fluorogenic substrate and generates a fluorescent signal to indicate the presence of the bacterium. This thesis outlines the efforts made towards functionalizing the F. nucleatum-responsive probe in stool samples to create a non-invasive screening test. RFD-FN1 is selective towards a heat-stable F. nucleatum protein, but its limit of detection is only 10^7 CFU/mL. Although able to detect spiked concentrations of F. nucleatum cells in processed stool samples, the use of heat, filtering, centrifugation, antibiotics, culturing or serial dilutions are not sufficient to detect the F. nucleatum that is naturally present in the diseased samples. Experiments designed to enrich the target concentration revealed that the target is not produced consistently in any growing condition tested. Size exclusion chromatography and mass spectrometry analysis identified five potential targets that RFD-FN1 may be responding to. Three candidate targets were cloned and purified, but they failed to induce RFD-FN1’s activity. Due to the COVID-19 pandemic, the purification of the final two proteins was not completed. Purifying the two candidate targets and testing their ability to induce RFD-FN1 represents future research efforts. If the target for the DNAzyme is confirmed, a reselection for a more sensitive DNAzyme, that can function in human stool, can be attempted. / Thesis / Master of Health Sciences (MSc)

Aptamers are nucleic acid ligands that bind to a specific target molecule. They are discovered by in-vitro selection, whereby binding sequences are selected from a large library of random sequences through iterative affinity steps. Aptamers are used as molecular recognition elements in aptamer-based, as such, creating aptamers with high affinity and specificity to their targets is important to the field. Ligands with two binding sites have been reported to have enhanced binding affinity than ligands with one binding site. To improve the quality of aptamers for downstream applications, multidomain selection is proposed as a new method for selecting aptamers compatible with dimerization. Here, we applied the multidomain selection approach to Fusobacterium nucleatum DnaK and produced aptamers that target the N-terminal domain (NTD) and the C-terminal domain (CTD) of DnaK. The top aptamer for DnaK-NTD had a Kd of 59.7 nM, and for DnaK-CTD had a Kd of 202.0 nM. However, the aptamers did not bind to the full-length DnaK and could not be dimerized. Multiple-site binding offers greater flexibility in the design of detection systems, which could provide higher selectivity and sensitivity than aptamers found through standard approaches. Validation of a method to discover aptamers compatible with dimerization would result in the development of a targeted approach to discover high-quality aptamers for bacterial proteins that can be used in bacteria-detection techniques. / Thesis / Master of Science (MSc)