Neoplasms Commons^™

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

Pancoast Syndrome Due To High Grade Anaplastic Tumor, Christian Almanzar, Seth Maxwell, Mauricio Gomez, Omar Ansari, Luis Silva

HCA Healthcare Journal of Medicine

The Pancoast tumor is an uncommon type of lung cancer that arises from within the superior sulcus. With most clinical manifestations occurring due to mass effect, Pancoast syndrome is a known complication that includes shoulder and arm musculoskeletal pain, Horner’s syndrome and neurological complications of the upper extremities, including weakness and atrophy. Even though adenocarcinoma is the most common cause of Pancoast syndrome among lung cancers, other malignancies can be responsible as well. Treatment is similar to that of other standard NSCLC treatments that include chemotherapy, radiation, immunotherapy and surgery. Here we report a patient with Pancoast syndrome secondary to …

Esophageal Cancer Complicated By A Distal Acquired Esophagopulmonary Fistula, Alexander D. Lake, Yousef Almuzaini, Aaron Jaffe, Joseph Staffetti, Mukesh Patel

HCA Healthcare Journal of Medicine

Esophageal respiratory fistulas, commonly found as a tracheoesophageal fistula (TEF), are abnormal connections between the esophagus and trachea. These can be congenital (infants) or acquired (malignancy). A more rare form of an esophageal respiratory fistula is an abnormal connection between the esophagus and the lung parenchyma—also known as an esophagopulmonary fistula. In our case, we present a middle-aged male with a history of esophageal cancer undergoing chemotherapy and radiation presenting into the intensive care unit for increasing shortness of breath and vomiting after eating found to have a rare form of a TEF causing his symptoms.

The Mitochondrial Protease Lonp1 Promotes Proteasome Inhibitor Resistance In Multiple Myeloma, Laure Maneix, Melanie A Sweeney, Sukyeong Lee, Polina Iakova, Shannon E Moree, Ergun Sahin, Premal Lulla, Sarvari V Yellapragada, Francis T F Tsai, Andre Catic

Faculty, Staff and Students Publications

Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to treat this incurable cancer. These drugs interfere with the main pathway of protein degradation and lead to the accumulation of damaged proteins inside cells. Despite promising initial responses, multiple myeloma cells eventually become drug resistant in most patients. The biology behind relapsed/refractory multiple myeloma is complex and poorly understood. Several studies provide evidence that in addition to the proteasome, mitochondrial proteases can also contribute to protein quality control outside of …

Mapk4 Promotes Prostate Cancer By Concerted Activation Of Androgen Receptor And Akt, Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M Ittmann, Chad J Creighton, Yingnan Bian, Yanling Meng, David R Rowley, Peter S Nelson, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Use Of Prame Immunostaining To Distinguish Melanoma In Situ From Lentigo Senilis, Hailey Olds, Sarah Utz, Darius Mehregan

Medical Student Research Symposium

PRAME (PReferentially expressed Antigen in MElanoma) is an antigen that is expressed by malignant cells in melanoma, as well as other cancers such as breast carcinoma, renal cell carcinoma, and leukemia. PRAME immunohistochemistry has proved effective in identifying malignant melanocytes in melanoma lesions, but it is unclear if it may be used to distinguish melanoma from benign melanocytic conditions, such as lentigo senilis. In particular, melanoma in situ may be confused with lentigo senilis clinically and histologically, thus PRAME immunostaining is potentially useful for differentiating these two lesions. We evaluated 31 samples of lentigo senilis, 26 of melanoma in situ, …

Clinical Utility Of Molecular Profiling In Recurrent Glioblastoma Multiforme, Rebecca P. Bystrom, Pavalan Selvam, Jens Rueter, Honey Reddi, Christine Lu-Emerson

Journal of Maine Medical Center

Introduction: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor found in adults. GBM has limited therapeutic options. Initial tumor sampling establishes the histopathologic diagnosis, identifies prognostic and therapeutic biomarkers, and provides an opportunity for molecular profiling. By contrast, the utility of repeat tumor sampling and molecular profiling in recurrent GBM is not well established.

Clinical Findings: We present a 69-year-old woman with GBM whose tumor recurred after standard treatment with temozolomide (TMZ) and concurrent radiation, followed by adjuvant TMZ. This patient had a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, which ordinarily predicts a favorable response to …

Invasive Mammary Carcinoma In Young Women, Jessica Ravert

Medical Imaging Senior Posters

Invasive Mammary Carcinoma in Young Women

Jessica Ravert

Gina Capitano Ed.D.,R.T. (R)

Abstract

This research is a case study of a 34-year-old patient that presented with a right breast lump measuring 1.9cm found to have invasive mammary carcinoma. Diagnostic mammogram and ultrasound were followed by ultrasound guided breast biopsy to make the diagnosis.

Breast cancer is the leading cause of cancer-related death in women between the ages of 15-39 inthe United States. Annual mammograms are recommended to begin at age 40, therefore younger women often do not have mammograms or breast ultrasounds unless they have symptoms. As a result, younger …

Collagen Fiber Regulation In Human Pediatric Aortic Valve Development And Disease, Cassandra L. Clift, Yan Ru Su, David Bichell, Heather Jensen Smith, Jennifer R. Bethard, Kim Norris-Caneda, Susana Comte-Walters, Lauren E. Ball, Michael A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Peggi M. Angel

Journal Articles: Eppley Institute

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Systemic Versus Local Injection Of Bone Marrow Mesenchymal Stem Cells On 5-Fluorouracil Treated Parotid Glands Of Albino Rats, Caroline Maged Massieh, Medhat El Zainy, Reham Magdy Amin, Iman Fathy

Dentistry

ABSTRACT Objective: Head and neck cancer is the sixth leading cancer by incidence worldwide and eighth by death. Recent reports revealed that, not only radiotherapy but also chemotherapy may induce xerostomia. The aim of this study was to compare the possible regenerative effect of BMSCs through systemic and local injections. Material and Methods: 52 male Albino rats were randomly divided into 4 groups: Group 1: 10 rats received 0.5 ml of PBS by injection. Group 2: 14 rats received an intraperitoneal injection of 5-FU drug. Group 3: 14 rats were injected the same dose of 5-FU then received an intraglandular …

Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock

Theses and Dissertations

The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …

Comparisons Of Oral, Intestinal, And Pancreatic Bacterial Microbiomes In Patients With Pancreatic Cancer And Other Gastrointestinal Diseases, Mei Chung, Naisi Zhao, Richard Meier, Devin C. Koestler, Guojun Wu, Erika De Castillo, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing.

Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each …

Epigenetic States Regulate Tumor Aggressiveness And Response To Targeted Therapies In Lung Adenocarcinoma, Fan Chen

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, 85% of which are lung adenocarcinomas (LUAD). Although molecular studies of NSCLC identified targetable mutations of some oncogenes including BRAF, EGFR and ALK, no targeted therapies exist for most cases. Cancer epigenetics is the study of epigenetic modifications, including histone modifications, that control gene expression in cancer. Recent advances have revealed numerous epigenetic abnormalities in human cancers, and targeting epigenetic regulators could be effective at reversing dysregulated epigenetic programs or driving sensitivity to other targeted therapies.

Inhibitors of the histone methyltransferase EZH2 have recently been approved as …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Unravelling The Potential Applications Of Extracellular Vesicles For The Clinical Management Of Melanoma Patients, Michael Edward Clark

Theses: Doctorates and Masters

Metastatic melanoma is the third most common cancer in Australia with global incidence increasing. After decades without effective systemic treatments for advanced melanoma, the advent of targeted and immune therapies has substantially improved patient survival. While this is encouraging, further research is needed as the majority of patients treated with targeted therapy ultimately develop drug resistance. Immunotherapy can achieve durable responses in many patients however, not all patients respond to current single or a combination of immune checkpoint inhibitors. Considering the cost and potential toxicities to patients being treated with these therapies, there is an urgent need to develop biomarkers …

Mucins, Gut Microbiota, And Postbiotics Role In Colorectal Cancer, Ramesh Pothuraju, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host …

Safety And Efficacy Of Fecal Microbiota Transplantation To Treat And Prevent Recurrent Clostridioides Difficile In Cancer Patients, Hiba Ali, Shruti Khurana, Weijie Ma, Yuanzun Peng, Zhi-Dong Jiang, Herbert Dupont, Hao Chi Zhang, Anusha S Thomas, Pablo Okhuysen, Yinghong Wang

Faculty, Staff and Students Publications

Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center.

Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline …