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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Colorectal cancer (CRC) is the third most common and third deadliest cancer worldwide with rising incidence rates attributed to environmental risk factors like diet. Investigating how these factors impact carcinogenesis requires an understanding of how transcriptional events evolve with respect to neoplastic progression. We employed meta-transcriptomics and latent trajectory modeling to establish a compendium of profiled healthy, adenoma, and CRC samples scored by their position along a pseudotemporal axis. By interpolating a continuous scale from cross-sectional data, dynamic processes occurring throughout disease progression can be analyzed more accurately. For example, smaller pseudotimes represented pre-malignant dysplasia and was characterized by cellular hyperproliferation downstream of genomic stress. Larger pseudotimes represented post-malignant progression and was characterized by a prominent stromal and inflammatory response. As dysregulated bile acid (BA) metabolism is intrinsically linked with diet and CRC development, we next assessed how neoplastic progression modulated colonic BA-related pathways. Pseudotemporal analysis delineated a role and clinical utility of the FGFR4-KLB-FGF19 pathway in disease progression. FGFR4 was an early CRC oncogene and the only FGFR that could be directly associated with tumorigenesis, suggesting that targeted inhibition may be a novel therapeutic modality. KLB's expression and prognostic profile was inverse to FGFR4, indicating a tumor suppressor role in early CRC. In particular, predictive informatics ascribed a functional role for KLB in opposing FGFR4-mediated dysplastic processes, which was validated using cellular models of differentiation as well as transgenic and morphological studies. FGF19 was also identified as an oncogene and putative blood-based CRC biomarker due to its endocrine properties. Immunodeficient mice transplanted with FGF19-expressing cells demonstrated supraphysiologic levels of circulating FGF19 that exerted potent endocrine effects targeting hepatic metabolism and enterohepatic recirculation of BAs. Collectively, the data provide clear evidence for the importance of the FGFR4-KLB-FGF19 complex in modulating CRC oncogenesis as well as its potential translational applicability for screening/diagnostic purposes.

Creating a universal-prime boost strategy using multi-specific T cells from the tumour infiltrating lymphocytes (TIL) population can enhance the success of adoptive T cell therapies (ACT). ACT, as a personalized living-drug, is often a last resort due to its extensive time, cost, and labor requirements, making it largely inaccessible. Vaccines encoding personalized tumour-associated antigens (TAA) have proven to be potent boosters for ACT. This combination has shown success in (1) promoting T cell proliferation in vivo and (2) inducing immune infiltration into the solid tumour microenvironment. TIL offer a plethora of TAA-specific T-cell receptors (TCRs) when successfully isolated and expanded. Synthetic receptors can be engineered into TIL to recognize any specified antigen, including those matched in vaccines. Previously, we validated combining ACT with an oncolytic virus vaccine (OVV) “boost” through a synthetic receptor to promote in vivo expansion of naïve splenocytes in a proof-of- concept TCR-transgenic synergetic murine model. Here, we report on the feasibility of isolating and engineering polyclonal, tumour-specific T cells from TIL and tumour- draining lymph nodes, evaluating them functionally. We further investigate the matched CAR/OVV system in another distinct TCR transgenic model and return to the first proof- of-concept model to uncover the biological mechanisms of our combination therapy to improve anti-tumour efficacy. Uniting a universal OV vaccine with a matched universal CAR creates an “off-the-shelf” combination, allowing any T cell product to be engineered. This approach reduces the resource burden of traditional ACT, making it more accessible to all cancer types. / Thesis / Master of Health Sciences (MSc) / Adoptive T cell therapy (ACT) uses a patient's immune cells to fight cancer but is often a last resort due to high costs and labor. Our research aims to make ACT more accessible by combining it with therapeutic cancer vaccines that can contain any protein, including cancer proteins, and boost ACT’s effectiveness. We engineered T cells with synthetic receptors to recognize the vaccine’s protein and developed a universal system pairing these T cells with a specially designed oncolytic virus vaccine (OVV). This combination promotes T cell expansion and improves immune response against tumours. We tested this system in multiple models, demonstrating enhanced T cell function and tumour targeting in one model, but challenges in another. Investigating the mechanisms, we sought to identify ways to improve the therapy’s efficacy. Our "off-the- shelf" solution reduces costs and resources, making this powerful cancer treatment more accessible to a wider range of patients.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

No description available.

No description available.

Class of 2009 Abstract / OBJECTIVES: Skin cancer is particularly prevalent in Arizona, with incidence rates ranking number two worldwide. Pharmacists are useful advocates for educating patients about the risks of skin cancer and methods of prevention. This study was conducted to assess pharmacists’ knowledge of skin cancer and their demographics and to evaluate how these factors impact skin cancer prevention patient counseling. METHODS: Participants were recruited using a listserv from pharmacists that were members of the Arizona Pharmacy Alliance or preceptors of the University of Arizona College of Pharmacy. Subjects completed an online questionnaire consisting of knowledge- based questions, questions about patient counseling preferences and subject demographics. RESULTS: The average score by pharmacists on the Skin Cancer and Sun Exposure Knowledge Indicator was 5.8 + 1.9. Pharmacists living in Arizona for longer times were more likely to know the minimum recommended SPF of sunscreen for adults to use when outdoors (p=0.003) and the factors associated with malignant melanoma prognosis/survival (p=0.004), but were less likely to know the definition of ABCD acronym (p=0.027). Having a family or friend diagnosed with any form of skin cancer or precancerous skin condition led to more pharmacists knowing the risk factors for developing melanoma (p=0.046) and knowing how often to apply water resistant sunscreen (p=0.035). CONCLUSIONS: The length of pharmacy practice in Arizona and having a family member or close friend affected by skin cancer significantly impacted a pharmacists’ knowledge of skin cancer.

The world of cancer care is a strange land to a person newly diagnosed with cancer. Like someone who leaves the familiarity of home and arrives in a foreign place, the person with cancer loses equilibrium and feels lost, experiences an assault on self-identity, and encounters an alien language and culture. It is this person who knocks as a stranger on the door of cancerland. Many philosophic and religious traditions obligate those receiving the stranger to provide a deep hospitality. One model of the practice of deep hospitality is summarized as door, table, space. When applied to the relationship between the cancer care provider and the patient/stranger, this hospitality can humanize the experience for both parties and is education in its elemental sense of drawing out and leading forth—into healing and wisdom.