Neoplasms Commons^™

Genetic Relationships And Therapeutic Options For Relapsed Acute Lymphoblastic Leukemia, Hailie Shertzer

Senior Honors Theses

Acute lymphoblastic leukemia (ALL) is the most common form of cancer among children and can be lethal to the adult population. Though 80% of patients with ALL reach complete remission after treatment, about 20% of those diagnosed fail to remain cancer-free. Genetic rearrangements are the hallmark of relapsed ALL, but the mechanism by which these rearrangements occur is still unclear. Recent research suggests these mutations may be detectable during initial diagnosis. If researchers are able to accurately assess the probability of relapse during diagnosis by analyzing the genome of the leukemic cells, the likelihood of administering effective therapy would increase. …

Association Between Sulfur-Metabolizing Bacterial Communities In Stool And Risk Of Distal Colorectal Cancer In Men, Long H. Nguyen, Wenjie Ma, Dong D. Wang, Yin Cao, Himel Mallick, Teklu K. Gerbaba, Jason Lloyd-Price, Galeb Abu-Ali, A. Brantley Hall, Daniel Sikavi, David A. Drew, Raaj S. Mehta, Cesar Arze, Amit D. Joshi, Yan Yan, Tobyn Branck, Casey Dulong, Kerry L. Ivey, Shuji Ogino, Eric B. Rimm, Mingyang Song, Wendy S. Garrett, Jacques Izard, Cutis Huttenhower, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Background and aims: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H₂S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men.

Methods: We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we …

The Relationship Between The Cervical Microbiome And Cervical Cancer Risk In Sub-Saharan Africa, Cameron G. Klein

School of Biological Sciences: Dissertations, Theses, and Student Research

Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Dysbiosis of the cervicovaginal microbiota, particularly involving sexually transmitted infections, is associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better understanding of the regional cervicovaginal microbiome is required. In this study, I establish the relationship between cervical cancer, HPV, HIV, cervicovaginal infections, and the cervicovaginal …

Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann

Medical Student Research Symposium

ATRX is a histone chaperone protein recurrently mutated in pediatric glioma. The mechanism which mediates the proliferative advantage of ATRX loss in pediatric glioma remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53^-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p < 0.0001) and CpG islands (p < 0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric glioblastoma (GBM) cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably, the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.

Impact Of Treatment Modality On Overall Survival In Localized Ductal Prostate Adenocarcinoma: A National Cancer Database Analysis, Chandler Bronkema, Sohrab Arora, Nikola Rakic, Akshay Sood, Deepansh Dalela, Jacob Keeley, Marcus Jamil, James O. Peabody, Craig G. Rogers, Mani Menon, Firas Abdollah

Medical Student Research Symposium

INTRODUCTION AND OBJECTIVE: Ductal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, and systemic therapy on overall survival (OS) in men with nonmetastatic ductal PCa.

METHODS: We retrospectively selected 2209 cases of ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database (NCDB). Exclusion of metastatic patients yielded a total sample of 1993 individuals. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy and no …

A Unique Schwannoma Of The Distal Hallux: A Case Study, Rebecca D. Stack Dpm, Brett Sachs Dpm Facfas, Dustin Kruse Dpm, Paul A. Stone Dpm, Facfas

Podiatry

No abstract provided.

Atypical Spindle Cell Lipomatous Tumor Under The Sesamoids In The Foot: A Case Report, Nilin M. Rao Dpm, Hani H. Saeed Dpm, Md, Facfas, Dustin Kruse Dpm, Bryan Raymond Dpm, Paul A. Stone Dpm, Facfas

Podiatry

Atypical spindle cell lipomatous (ASCL) tumors have a distinct histological and clinical presentation, rarely presenting in the foot. With the sub-sesamoidal location of this neoplasm found in our case report being an unusual location for atypical spindle cell lipomatous tumors to present, the purpose of our case report was to present the clinical presentation, histology/pathology, method of resection and outcome of our patient on follow-up to provide a framework for other surgeons on how to approach these neoplasms in the future.

Reverse Takotsubo-Like Cardiomyopathy And Pheochromocytoma, Patryk Purta, Dmitriy Scherbak Do, Michael Gruber Md, Oliwier Dziadkowiec

Cardiology

No abstract provided.

Adrenocortical Carcinoma: A Stressful Diagnosis, Shabnam Khoie Do, Dmitriy Scherbak Do

Internal Medicine

Introduction: Adrenocortical carcinoma (ACC) is a rare and biologically aggressive malignancy. The incidence of ACC is between 0.7-2 cases per million, accounting for 0.05-2% of all malignant tumors. Cortisol-producing carcinomas are the most common, with clinical features consistent with hypercortisolism: refractory hypertension, glucose intolerance, and central obesity. We present a case of a 75-year-old male with a cortisol-secreting variant of adrenocortical carcinoma.

Case Description: A 75 year-old male with a prior medical history significant for refractory hypertension on multiple anti-hypertensives including hydrochlorothiazide, type two diabetes mellitus, and untreated obstructive sleep apnea, presented to the emergency department with a blood pressure …

Rectal Neuroendocrine Tumor In A Patient With Chek2 Mutation, Shefali Khanna, Deena Dahshan, Erin Fankhanel, Doreen Griswold, Lynne J. Goebel

Marshall Journal of Medicine

We provide new information about CHEK2 mutation in association with a rectal neuroendocrine tumor (NET). A 67-year-old Caucasian woman diagnosed with estrogen receptor positive ductal carcinoma in situ breast cancer underwent genetic testing, revealing a CHEK2 mutation that prompted her to have a colonoscopy. This revealed a polyp with immunohistochemical staining positive for markers classically associated with NETs. Six-month follow up surveillance colonoscopy after initial polyp removal found no evidence of recurrence. While the CHEK2 mutation is known to be associated with adenocarcinomas, there is only one other reported case of its association with NETs.

Anxiety-Related Issues In Cancer Survivorship, Maresi A. Berry-Stoelzle, Anna C. Mark, Peter Kim, Jeanette M. Daly

Journal of Patient-Centered Research and Reviews

Purpose: The purpose of this qualitative study was to examine patient opinions about anxiety in cancer survivorship, particularly the role of the primary care provider in management of anxiety related to the trajectory of long-term cancer survivorship.

Methods: Respondents to a mass email (N = 22,000) were invited to participate in 1 of 3 institutional review board-approved focus group meetings. Inclusion criteria were being an adult patient older than 25 years of age, having any type of cancer diagnosis, and being at least 18 months from treatment. The following specific issues were discussed: role of the primary care provider …

The Nuclear Legacy In Appalachia, Michele Morrone, Harold Perkins

Journal of Appalachian Health

Nestled in the rolling hills of Appalachia Ohio is a reminder of the role that the region played in winning the Cold War. For more than 40 years in rural Pike County, the 3,700-acre Portsmouth Gaseous Diffusion Plant (PORTS), or the “A-Plant” as the locals refer to it, enriched uranium for use in nuclear weapons. While the facility produced nuclear fuel for national security, it simultaneously exposed plant workers to chemicals and radiation and discharged pollution into the surrounding community. The A-Plant is now being demolished and the site repurposed. However, the site continues to affect the community as, for …

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

A Rare Case Of Trichilemmal Carcinoma: Histology And Management, Lisa F. Fronek, Allyson Brahs, Maheera Farsi, Richard Miller

West Florida Division GME Research Day 2020

Trichilemmal carcinoma (TC) is a rare, malignant, adnexal neoplasm that is derived from the outer root sheath (ORS) of the hair follicle. These tumors predominantly occur in elderly patients on sun-exposed areas, specifically on the head and neck with the face defined as the most common location. The mean age of diagnosis is 70 years old with a slight male predominance. These lesions are commonly identified as a papular, nodular, and sometimes, exophytic. They generally arise de-novo, but may also derivate from an underlying proliferating trichilemmal cyst with a loss of p53, a seborrheic keratosis, a nevus sebaceous, or a …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon

Department of Food Science and Technology: Faculty Publications

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Functional Characterisation Of Cancer-Associated Fibroblasts From Nasopharyngeal Carcinoma, Wee Lin Wong

Student Works (2020-2029)

Nasopharyngeal carcinoma (NPC) remains a major health issue in Southern China and Southeast Asia where the disease is endemic. Whilst the cure rate for early stage NPC is high, patients often present with late stage diseases and have a 5-year survival rate of less than 50%. NPC patients often suffer from severe treatment side effects because of the location of the tumours that is in proximity to various important organs in the head and neck region. Therefore, alternative therapeutic approaches are needed to improve the treatment outcomes and reduce patient morbidity. Targeted therapies are not in routine use to treat …