Medicine and Health Sciences Commons^™

Mutational Patterns In Chemotherapy Resistant Muscle-Invasive Bladder Cancer., David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y.T. Chen, R. Katherine Alpaugh, Jean Hoffman-Censits, Levi A. Garraway, Gad Getz, Scott L. Carter, Joaquim Bellmunt, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen

Department of Medical Oncology Faculty Papers

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts …

Sensitive Droplet Digital Pcr Method For Detection Of Tert Promoter Mutations In Cell Free Dna From Patients With Metastatic Melanoma, Ashleigh C. Mcevoy, Leslie Calapre, Michelle Pereira, Tindaro M. Giardina, Cleo Robinson, Muhammad A. Khattak, Tarek M. Meniawy, Antonia L. Pritchard, Nicholas K. Hayward, Benhur Amanuel, Michael J. Millward, Mel R. Ziman Dr, Elin S. Gray

Research outputs 2014 to 2021

Background:

Currently mainly BRAF mutant circulating tumor DNA (ctDNA) is utilized to monitor patients with melanoma. TERT promoter mutations are common in various cancers and found in up to 70 % of melanomas, including half of BRAF wildtype cases. Therefore, a sensitive method for detection of TERT promoter mutations would increase the number of patients that could be monitored through ctDNA analysis.

Methods:

A droplet digital PCR (ddPCR) assay was designed for the concurrent detection of chr5:1,295,228 C > T and chr5:1,295,250 C > T TERT promoter mutations. The assay was validated using 39 melanoma cell lines and 22 matched plasma and …

Meta-Regression: Prognostic Models As Objective Predictors Of Mortality Among Icu Cancer Patients, Sheila Donnell

Nursing Theses and Dissertations

Cancer patients admitted to the intensive care unit (ICU) may be experiencing complications of disease or treatment-related effects. While acute complications related to disease and/or its therapeutic management vary in severity, the approach to ICU-centered care is complicated by actual versus perceived risks of poor outcomes. Prognostic models that inform clinical judgment of nurses and physicians may prove helpful in this population. The Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) are ICU-based models predicting 30-day mortality among the general ICU population. Although studies have been …

Abstracts From The 23rd Annual Health Care Systems Research Network Conference, March 21–23, 2017, San Diego, California

Journal of Patient-Centered Research and Reviews

This proceedings supplement includes selected abstracts presented at the 23rd annual conference of the Health Care Systems Research Network (HCSRN), held March 21–23, 2017, in San Diego, California. Formerly called the HMO Research Network, HCSRN aims to improve individual and population health through research that connects the resources and capabilities of its member health care systems.

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie

Mahurin Honors College Capstone Experience/Thesis Projects

With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay …

Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using …

Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.

Pakistan - Country Profile Of Cancer And Cancer Control 1995-2004, Yasmin Bhurgri, Asif Bhurgri, Sania Nishter, Ashfaq Ahmed, Ahmed Usman, Shahid Pervez, Naila Kayani, Rashida Ahmed, Sheema H. Hassan, Ahmed Riaz, Hadi Bhurgri, Imtiaz Bashir

Rashida Ahmed

No abstract provided.

Breast Cancer Patient Preparedness For Transition To Survivorship: Individualized Survivorship Care Plans, Kimberly Beringer

Master's Projects and Capstones

Purpose. For breast cancer survivors, after-effects of surgery, radiation and chemotherapy can be substantial, and recurrence is a concern requiring constant surveillance. National healthcare organizations have promulgated guidelines that include providing individualized survivorship care plans (SCP’s). At a northern California oncology department, SCP’s will be prepared for breast cancer patients and delivered in-person by the oncology nurse navigator (ONN).

Method. The author worked with the ONN to develop the format and content requirements for the SCP’s. The ONN prepared individualized plans for patients and scheduled in-person appointments to deliver the SCP’s. A feedback survey to assess preliminary impact was then …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations & Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee AYY, Levin MN, Bake RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-153. doi: 10.1056/NEJMoa025313

Gastrointestinal Stromal Tumor Induced Hypercalcemia, Aram Barbaryan, Stefania Bailuc, Padma Poddutoori, Aida Richardson, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D₃ mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D₃. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our …

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - 2020

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)⁷, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. …

Using A Conformal Water Bolus To Adjust Heating Patterns Of Microwave Waveguide Applicators, Paul R. Stauffer, Dario B. Rodrigues, Randolph Sinahon, Lyndsey Sbarro, Valeria Beckhoff, Mark Hurwitz

Department of Radiation Oncology Faculty Papers

Background: Hyperthermia, i.e., raising tissue temperature to 40-45°C for 60 min, has been demonstrated to increase the effectiveness of radiation and chemotherapy for cancer. Although multi-element conformal heat applicators are under development to provide more adjustable heating of contoured anatomy, to date the most often used applicator to heat superficial disease is the simple microwave waveguide. With only a single power input, the operator must be resourceful to adjust heat treatment to accommodate variable size and shape tumors spreading across contoured anatomy. Methods: We used multiphysics simulation software that couples electromagnetic, thermal and fluid dynamics physics to simulate heating patterns …

Biological Functions Of Cdk5 And Potential Cdk5 Targeted Clinical Treatments., Alison Shupp, Mathew C. Casimiro, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK's T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate …

Thyroid Hormone Receptor Ss (Trß) Regulation Of Runt-Related Transcription Factor 2 (Runx2) In Thyroid Tumorigenesis: Determination Of The Trß Nuclear Protein Complexes That Associate With The Runx2 Gene., Thomas Howland Taber

Graduate College Dissertations and Theses

Thyroid Tumorigenesis is typically a well understood process, with well delineated oncogenic factors. Follicular and papillary thyroid cancers are typically survivable, with 5-year survival rates being >95% for Stage I-III of both cancer types. Anaplastic thyroid cancer, in contrast, lacks this prognosis, and is the most lethal of all endocrine-related cancers. The median survival time after a diagnosis is generally between 6-8 months, with a 5-year survival rate of <10%. Current treatment for anaplastic thyroid cancers routinely meet roadblocks, as resistance is quickly developed. Even non-discriminatory kinase inactivators, such as sorafenib, which are generally considered a drug of last resort, are unable to effect survival rates. As such, there is a clear need for further investigation of the causes of anaplastic thyroid cancer mechanisms.

Previous work in the Carr lab revealed a novel regulatory pathway of an oncogene that is associated with several other endocrine-related cancers, as well as other non-endocrine-related cancers. Specifically, the Runt-related …

Using Tcr Transgenic, Gp100 Reactive T Cells And Checkpoint Inhibition To Target Lymphangioleimyomatosis, Christian Ankney

Master's Theses

Lymphangioleiomyomatosis (LAM) is a low-grade neoplastic disease affecting primarily women. It is characterized by cystic lung disease as well as renal and retroperitoneal tumors called angiomyolipomas and lymphangiomas. Tumor cells have smooth muscle features as well as neuroendocrine cell surface markers, and the disease can be diagnosed by HMB45 staining of tumor cells. We questioned whether expression of melanocytic antigens, specifically gp100, creates an opportunity to treat LAM by adoptive T cell transfer. LAM lung lesions demonstrate poor immune surveillance, therefore adoptive T cell transfer could offer benefits in this disease.

A link was made between melanoma and depigmenting vitiligo …

Physical Activity And Survival Among Long-Term Cancer Survivor And Non-Cancer Cohorts, Anthony Gunnell, Sarah Joyce, Stephania Tomlin, Dennis Taaffe, Prue Cormie, Robert Newton, David Joseph, Nigel Spry, Kristjana Einarsdottir, Daniel A. Galvao

Research outputs 2014 to 2021

Evidence suggests physical activity improves prognosis following cancer diagnosis; however, evidence regarding prognosis in long-term survivors of cancer is scarce. We assessed physical activity in 1,589 cancer survivors at an average 8.8 years following their initial diagnosis and calculated their future mortality risk following physical activity assessment. We also selected a cancer-free cohort of 3,145 age, sex, and survey year group-matched cancer-free individuals from the same source population for comparison purposes. Risks for cancer-specific mortality and all-cause mortality in relation to physical activity levels were estimated using Cox regression proportional hazard regression analyses within the cancer and non-cancer cohorts. Physical …

The "Eyes" Have It?-Intra- And Inter-Observer Reproducibility Of The Pd-L1 Companion Diagnostic Assay, Steven G. Gray, Mark Wright, Stephen Finn

Articles

No abstract available.

Cancer Care Annual Report 2016-2017, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center. This report has a focus on sarcomas.

The Experience Of Qigong Among Women Cancer Survivors, Jennifer Sveund

Antioch University Full-Text Dissertations & Theses

Research has shown that qigong can be beneficial for a variety of health related conditions; However, evidence suggests that in the United States, a lack of well designed clinical trials limits the efficacy of qigong in the context of cancer treatment. Research has indicated that careful consideration should be given to the design of randomized control trials using qigong due to the conflicting philosophical methodologies. In the United States, qigong has been under investigated, particularly lacking are qualitative inquiries into qigong use and cancer survivorship. This study is an interpretative phenomenological inquiry that sought to understand women’s experience of qigong …

The Lived Experience Of Intersectionality Among African American Women With Breast Cancer, Teri D. Armour Burton

Dissertations

African American women (AAW) continue to have breast cancer mortality rates that are 42% higher than White women (De Santis et al., 2015). Researchers suggest that an epistemological approach that integrates the biomedical and feminist models would be more effective in addressing health disparities. The concept of intersectionality, which grew out of the Black feminist movement, provides a lens in which to view the lived experiences of AAW with breast cancer. The intersectionality paradigm attempts to address the marginalized, oppressive, intersecting social existence of AAW through the examination of identity, social class, and power.

This qualitative study applied a descriptive …

Frontiers In Precision Medicine Ii: Cancer, Big Data And The Public, Emily Coonrod, Jorge L. Contreras, Willard Dere, Jeffrey Botkin, Leslie Francis, Jim Tabery

Utah Law Faculty Scholarship

Precision medicine is being developed within a complex landscape of public policy, science, economics, law, and regulation. In these and other policy areas, the goal of developing individually-tailored therapies poses novel challenges for health care research, delivery and policy. In this symposium, a range of experts in genetics, medicine, bioinformatics, intellectual property, health economics and bioethics identified and discussed many of the pressing questions raised by the development and practice of precision medicine. These and other issues will need to be taken into account as precision medicine moves ahead and becomes the standard of medical practice and care in the …

Using Technologies To Support The Social And Academic Engagement Of Young People With Cancer, Owen Michael Donovan

Legacy Theses & Dissertations (2009 - 2024)

Situated in the larger questions of how to support the educational engagement and positive psychosocial development of young people with cancer, the purpose of this exploratory study was to address gaps in the literature and build understanding of how young people use digital and Internet-connected technologies in ways that support their social and academic engagement. Through a multiple case-design, I examined the school-based and everyday (outside of school) technology uses of five young people. This study found that the cancer experience changed or reframed a young person’s motivational engagement with school. Doing well academically was a sign of a normalcy …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Provider Education: Managing Depression In Cancer Patients, Nicole Leonard

Family Medicine Clerkship Student Projects

Depression is more prevalent and less often treated in cancer patients compared to the general population. Cancer can increase the risk of depression in multiple different ways, but depression can also increase the risk of cancer. Untreated depression in cancer patients can increase the risk of metastasis and worsen prognosis. The purpose of this project is to educate providers on the connection between mental health and cancer as well as provide them resources on how to approach and manage patients with cancer and depression.

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …