Translational Medical Research Commons^™

Sexual Dysfunction After Rectal Cancer Treatment, Sarah M. Popek

Clinical and Translational Science Center Scholarly Output

Introduction: Treatment for rectal cancer results in sexual dysfunction. Sexual function is a component of the HR-QOL (health related quality of life) measures. The incidence of sexual dysfunction following treatment for rectal cancer and its impact on the HR-QOL is not well delineated, particularly on women.

Objectives: To prospectively assess the degree of sexual dysfunction that occurs after treatment for Stage I-III rectal cancer and the corresponding short term (<3 months) and long term (<2 years) effect on the Quality of Life measure for oncology (QOL-30).

Methods: Validated questionnaires will be administered to assess sexual function and quality of life. The International Index of Erectile Dysfunction will be administered to male patients and …

The Role Of Rassf5 On Cell Growth And Hippo Signaling In Rhabdomyosarcoma, Megan Garver, Lee Helman, Md, Katrina Slemmons, Phd

Phase 1

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Dysregulation of the Hippo pathway, a signaling cascade that regulates many biological processes, is associated with many human cancers. The goal of my project was to delete RASSF5, a regulator of the Hippo pathway, in RMS cells utilizing CRISPR/Cas9 and then to evaluate how the absence of RASSF5 affects RMS cell growth and Hippo signaling, with and without DNMTi Tx.

Methods: A lipofectamine transfection was performed in two different RMS cell lines, Rh30 & RD, in which two different CRIPSR/Cas9 vectors with RASSF5 guide RNA were introduced. …

Protocol For Ground Glass Opacity, Elissa Goldman

Phase 1

Rationale: Pure ground glass opacities (GGO), identified incidentally or on lung cancer screening, may indicate pre-invasive subtypes of lung adenocarcinoma. These neoplasms typically demonstrate indolent patterns of growth, and Fleischner Society guidelines recommend up to five years of serial imaging. Our aim was to determine the frequency of diagnosed lung adenocarcinoma arising from GGO detected beyond 5 years of CT surveillance.

Methods: We reviewed all pathologic diagnoses of lung adenocarcinoma (n=442) between 2016 and 2018 of a tertiary academic hospital and National Cancer Institute-designated cancer center to identify all cancers that arose from ground glass opacities detected on CT scan. …

Conjunctival Melanoma: Features Based On The Fitzpatrick Skin Type (Fst) In 540 Patients At A Single Ocular Oncology Center, Sunihidi Ramesh, Antonio Yaghy, Lauren A. Dalvin, Sara E. Lally, Jerry A. Shields, Carol L. Shields

Phase 1

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma.

Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average …

Early Perioperative Fluid Benchmarking To Predict Pancreaticoduodenectomy (Pd) Outcomes, David Moskal, Carrie D. Walsh, Sofia Duque, Charles Yeo, Md, Facs, Harish Lavu, Md, Facs

Phase 1

Introduction: PD is a complex operation associated with a marked systemic inflammatory response and significant fluid shifts. Establishing a benchmark for ideal perioperative fluid management is critical to optimising PD patient recovery.

Methods: In this retrospective study, we evaluated perioperative fluid data for patients undergoing PD. We compared an optimal benchmark group who were discharged home by postoperative day five (≤5day) to a group of patients with an in hospital recovery greater than ten days (≥10day).

Results: Seventy-six patients who underwent PD between June 2015 and November 2016 were evaluated. The ≤5day group had a significantly lower intraoperative fluid administration …

Manipulation Of Genome Integrity Signaling Axes Contributing To Prostate Cancer Aggressiveness, Frank Duan, Veronica Rodriguez-Bravo, Phd

Phase 1

Introduction: Prostate cancer (PC) is one of the leading causes of death in men, and despite current treatment options patients can develop aggressive disease that spreads to other parts of the body. Little research has focused to date on the effect of centrosome biology in the pathogenesis of PC.

Methods: Two metastatic PC cell lines, DU145 and 22Rv1, as well as highly aggressive derivatives generated in Dr. Rodriguez-Bravo lab (docetaxel-resistant; (DR) variants) were compared through various experiments to determine differences in centrosome proteins expression and functionality. All cells (DU145 /DR and 22Rv1 /DR) underwent electroporations with siRNAs to knockout …

Ethnic Differences In Germline Genetic Testing For Breast Cancer, Kathryn Dent, Rebecca J. Jaslow, Md

Phase 1

Introduction: Ethnic variations in uptake of genetic testing and differences in findings of germline mutations within ethnic groups, are not well understood. The goal of this research is to assess for any such differences or similarities within a genetic counseling and testing program at an urban Cancer Center.

Methods: This is a non-comparative, descriptive epidemiology study assessing individuals with a diagnosis of breast cancer undergoing genetic counseling at the TJUH Sidney Kimmel Cancer Center in Philadelphia between 2014 and 2019. Data were compiled onto Research Electronic Data Capture (REDCAP) and analyzed statistically.

Results: Patients with Breast Cancer (n=1075) were included …

Surgical Resection Of Convexity Meningiomas: A Single Center Retrospective Analysis, Haley Wendt, Michael Baldassari, Donald Ye, Kevin Judy

Phase 1

Introduction: Dural convexity meningiomas (CMs) are the most common primary intracranial tumors. Although surgical resection carries relatively low risk, it is necessary to quantify perioperative risks from a large patient cohort and identify factors contributing to short-term and long-term outcomes.

Methods: Patients who underwent craniotomy for resection of CMs between January 2012-December 2018 at a single large academic center were reviewed for pre-operative demographics, radiographic characteristics, and post-operative outcomes.

Results: 122 cases of CMs were identified. Common presenting symptoms included headache (39.3%), seizure (27.0%) and weakness/paralysis (18%). CMs were located over frontal, parietal, temporal, and occipital lobes in 57.4%, …

The Presence Of Gc-C In Extracellular Vesicles Secreted By Colorectal Cancer Cells, Alexandre Martinez, Adam E. Snook

Phase 1

Background: Guanylyl Cyclase C (GC-C) is a membrane-bound protein found on intestinal epithelial cells involved in the activation of CFTR. This protein has previously been involved in the development of colorectal cancer.

Extracellular vesicles (EVs) are bilayered vesicles of varying size (30 to 1,000 + nm in diameter) that believed to be secreted by all cells in the human body. In the past decade, EVs have garnered attention due to their impact in the field of oncology, where they have been shown to potentially serve as biomarkers for various cancers.

In this study, we looked at the EVs secreted …

Statistics Of Tumor Micro-Environment, Brenton Maisel, Inna Chervoneva

Phase 1

Introduction: Immune cells play a prominent role in keeping tumors suppressed, but how the distribution of these immune cells within a tumor’s microenvironment remains poorly understood. The long-term goal of this project is to study how statistical spatial distributions of different immune cells is associated with clinical outcome. The first objective is developing an algorithm for identifying different types of immune cells.

Methods: The data motivating this project includes spatial localization information (x-y coordinates) and expression levels of immune cell CD markers quantified by immunofluorescence immunohistochemistry (IF-IHC) in ~1,500 cases of invasive breast cancer. Using expression levels of CD markers …

Impact Of In-House Specialty Pharmacy On Access To Novel Androgen Axis Inhibitors In Men With Advanced Prostate Cancer, Anna Driscoll, Nathan Handley, Md, Mba, Adam Binder, Siobhan Henry, W. Kevin Kelly, Do

Phase 1

Introduction: Novel androgen axis inhibitors are standard of care treatments in advanced prostate cancer. The billed amounts for these medications are often very high, which may create significant financial toxicity for patients and lead to delays in treatment. Our institution implemented an in-house specialty pharmacy in 2014, that provides these medications and evaluates copay assistance options for all patients. We evaluated the program’s impact on out of pocket cost (OOP) and turnaround time (TAT).

Methods: We reviewed available internal specialty pharmacy records to identify prescriptions for abiraterone or enzalutamide filled between 1/1/17 and 12/31/18. Payments were stratified by primary payment …

Hepatocellular Carcinoma Treated With Microwave Ablation Prior To Liver Transplantation, Nicole Wagner, Amanda Smolock, Michael Markovitz, Varun Danda, Christopher Neely, Warren Maley, Jesse Civan, Colette Shaw

Phase 1

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA.

Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, …

Determining The Role Of Surgery In Diagnosis And Treatment Of Primary Cns Lymphoma, Tyler Fox, Michael Baldassari, Lohit Velagapudi, Karim Hafazalla, Christopher J. Farrell, Md, James J. Evans, Md, David W. Andrews, Md, Kevin Judy, Md, Donald Ye, Md

Phase 1

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare entity typically treated with a combination of chemotherapy and radiation. The role of surgery is controversial, and biopsy may be non-definitive or injurious. We review our series of stereotactic and excisional biopsy as well as surgical debulking of PCNSL to quantify overall risk and benefits.

Methods: Patients with biopsy-confirmed intracranial PCNSL were identified from a large singlecenter academic institution between 2012-2018. Preoperative factors and perioperative outcomes were retrospectively reviewed.

Results: A total of 61 cases of PCNSL were identified. Most patients presented with confusion (23.0%), weakness/paralysis (19.7%), and gait disturbance …

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Coordinating An Oncology Precision Medicine Clinic Within An Integrated Health System: Lessons Learned In Year One, Michael A. Thompson, Jennifer J. Godden, Deborah Wham, Antony Ruggeri, Michael P. Mullane, Amanda Wilson, Shamsuddin Virani, Scott M. Weissman, Brenda Ramczyk, Pamela Vanderwall, James L. Weese

Journal of Patient-Centered Research and Reviews

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual’s genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM’s potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health …

Cyclin D1-Mediated Microrna Expression Signature Predicts Breast Cancer Outcome, Guangxue Wang, Michael Gormley, Jing Qiao, Qian Zhao, Min Wang, Gabriele Disante, Shengqiong Deng, Lin Dong, Timothy G. Pestell, Xiaoming Ju, Mathew C. Casimiro, Sankar Addya, Adam Ertel, Ayden Tozeren, Qinchuan Li, Zuoren Yu, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood.

Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes.

Results: Hierarchical clustering of …

Implementation Of A Low-Cost Unna Boot Alternative As Adjunctive Treatment For Kaposi Sarcoma, Alexander Robert Mills, Edith Tonui, Sonak Pastakia, Rakhi Karwa, Phelix Were

Engagement & Service-Learning Summit

There are 6 million people living with HIV; 70% reside in Sub-Saharan Africa (SSA). Furthermore, 1.1 million deaths occur due to opportunistic infections (OIs) that can be minimized with antiretroviral therapy. In Kenya, Kaposi Sarcoma (KS) is an especially debilitating OI that presents with dermatologic lesions; magnifying the stigma that patients with HIV face physically and psychosocially. Dermatology research is underway to determine the effectiveness of an unna boot (medicated, layered compression dressing) to speed the healing of these lesions with anecdotal success. Commercially available unna boot products are too expensive and not readily available in SSA. Clinicians from Purdue …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Impact Of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer, Jonathan M. Loree

Dissertations and Theses (Open Access)

Introduction: Mutations in KRAS/NRAS (RAS) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to evaluate how NGS can optimally define RAS mutant CRC and the role of relative mutant allele frequency (rMAF) as a biomarker.

Methods: Using institutional and public cohorts of mCRC patients with NGS results, we described the prevalence and clinical impact of atypical (not in current guidelines) and low rMAF RAS mutations (RAS MAF by the MAF of the mutated gene with …

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …

Conference Proceedings: Aurora Scientific Day 2017

Journal of Patient-Centered Research and Reviews

This supplement includes select abstracts presented at the 43rd Annual Aurora Scientific Day research symposium on May 24, 2017. Aurora Scientific Day hosts a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system headquartered in Milwaukee, Wisconsin.

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

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

Unique Breast Cancer Features Within The Vietnamese Population, Polly Niravath, Melissa Bondy, Susan G. Hilsenbeck

Journal of Health Disparities Research and Practice

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts.

PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population.

METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year …

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

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 …

Her4 Promotes A Stem-Like Phenotype In Osteosarcoma, Rocio K. Rivera-Valentin

Dissertations and Theses (Open Access)

Metastatic disease to the lungs is the primary cause of death for patients with pediatric osteosarcoma (OS). OS has a high degree of heterogeneity and genomic instability, making understanding the pathogenesis and drivers of metastasis of this disease challenging. In an effort to explain tumoral heterogeneity, the tumor initiating cell model (TIC) states that tumors are composed of cells that form the majority of the tumor and are terminally differentiated. This model however, attributes tumorigenesis, metastasis and chemoresistance to a distinct cell population with a stem-like phenotype that can be identified using selective markers. OS appears to follow this model …

The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain. Here, we discuss NG2 …