Neoplasms Commons^™

Predicting Lymph Node Metastasis In Non-Small Cell Lung Cancer: Prospective External And Temporal Validation Of The Hal And Homer Models, Gabriela Martinez-Zayas, Francisco A Almeida, Lonny Yarmus, Daniel Steinfort, Donald R Lazarus, Michael J Simoff, Timothy Saettele, Septimiu Murgu, Tarek Dammad, D Kevin Duong, Lakshmi Mudambi, Joshua J Filner, Sofia Molina, Carlos Aravena, Jeffrey Thiboutot, Asha Bonney, Adriana M Rueda, Labib G Debiane, D Kyle Hogarth, Harmeet Bedi, Mark Deffebach, Ala-Eddin S Sagar, Joseph Cicenia, Diana H Yu, Avi Cohen, Laura Frye, Horiana B Grosu, Thomas Gildea, David Feller-Kopman, Roberto F Casal, Michael Machuzak, Muhammad H Arain, Sonali Sethi, George A Eapen, Louis Lam, Carlos A Jimenez, Manuel Ribeiro, Laila Z Noor, Atul Mehta, Juhee Song, Humberto Choi, Junsheng Ma, Liang Li, David E Ost

Faculty, Staff and Students Publications

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers.

RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers?

STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. …

A Cancer Ubiquitome Landscape Identifies Metabolic Reprogramming As Target Of Parkin Tumor Suppression, Ekta Agarwal, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Jagadish C Ghosh, Lucia Languino, Valentina Vaira, David W Speicher, Dario C Altieri

Department of Cancer Biology Faculty Papers

Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

Cd8+ T Cells Inhibit Metastasis And Cxcl4 Regulates Its Function, Robiya Joseph, Rama Soundararajan, Suhas Vasaikar, Fei Yang, Kendra L Allton, Lin Tian, Petra Den Hollander, Sevinj Isgandarova, Monika Haemmerle, Barbara Mino, Tieling Zhou, Crystal Shin, Melisa Martinez-Paniagua, Aysegul A Sahin, Jaime Rodriguez-Canales, Juri Gelovani, Jeffrey T Chang, Ghanashyam Acharya, Anil K Sood, Ignacio I Wistuba, Don L Gibbons, Luisa M Solis, Michelle C Barton, Navin Varadarajan, Jeffrey M Rosen, Xiang H Zhang, Sendurai A Mani

Faculty, Staff and Students Publications

Background

The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.

Methods

We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as …

Benign Myoepithelioma Of The Soft Palate: An Unusual Clinical Entity, Marianna Guadalupe Mireles, Angelica Julián, Fabiola Salgado-Chavarría, Guillermo Manuel González

Faculty, Staff and Students Publications

Myoepitheliomas are rare benign tumours that affect the exocrine glands and are sporadically located in the salivary glands. The most common location of myoepithelioma in the oral cavity is the parotid gland and it is seldom encountered in the palate. The diagnosis of this entity is challenging since its clinical presentation may resemble those of more common neoplasms, rendering a complex histopathological diagnosis. The aim of the present case report is to describe an unusual case of myoepithelioma of the soft palate in a male patient, which developed as an asymptomatic, slowly growing mass. The tumour was assessed with histopathological …

Microrna-26a-5p As A Potential Predictive Factor For Determining The Effectiveness Of Trastuzumab Therapy In Her-2 Positive Breast Cancer Patients, Sadra Samavarchi Tehrani, Ehsan Zaboli, Farzin Sadeghi, Soraya Khafri, Ansar Karimian, Mahnoosh Rafie, Hadi Parsian

BioMedicine

Background: Breast cancer (BC) is known as the most prevalence type of cancer among women. Trastuzumab, as a cancer drug, has been used broadly in human epidermal growth factor receptor 2 (HER-2) positive BC patients. On the other hand, accumulating evidence has demonstrated that microRNAs involved in pathogenesis BC. Hence, we aimed to investigate the effect of trastuzumab on the expression levels of microRNA-26a in HER-2positiveBC patients.

Methods: This study was conducted on HER-2 positive BC patients and HER-2 Negative BC patients. Serum expression of microRNA-26a were detected by real-time PCR. Then, we assessed the correlation of microRNA-26a level with …

Replication Protein A (Rpa) Targeting Of Uracil Dna Glycosylase (Ung2), Derek Chen, Brian P Weiser

Rowan-Virtua Research Day

Replication Protein A (RPA) is a single stranded DNA binding protein which stabilizes ssDNA for replication and repair. One function of RPA is to bind the DNA repair enzyme uracil DNA glycosylase (UNG2) and direct its activity towards ssDNA dsDNA junctions.

UNG2 removes uracil bases from DNA which can appear through dUMP misincorporation or through cytosine deamination. If uracil is present instead of a cytosine, then the original GC pair becomes a GU pair. The uracil will then base pair to adenine in the replicated daughter strand. This results in a GC → AT mutation that could contribute to cancer …

Novel Technology Enables Diagnostic Ultrasound Machine To Treat Hepatocellular Carcinoma In Mice, Ryan Morrison, Mrigendra B. Karmacharya, Chandra M. Sehgal

Rowan-Virtua Research Day

An off-the-shelf diagnostic transducer (ULTRASONIX C5-2) was modified with custom-built circuitry to enable the transducer to produce therapeutic ultrasound in order to ablate hepatocellular carcinomas grown in immunodeficient athymic nude mice (25-35 g; Charles River Laboratories, Wilmington, MA, USA). The therapeutic antivascular ultrasound (AVUS) produced by the off-the-shelf abdominal transducer was unfocused, continuous 2.8MHz ultrasound targeting contrast-enhancing perflutren lipid microbubbles within tumor vasculature. Previous research with a dedicated physiotherapy ultrasound machine (D150 Plus, Dynatronics Corp., Salt Lake City, UT, USA) targeting similar hepatocellular carcinomas showed disrupted tumor neovasculature and irreparable dilation of tumor capillaries with subsequent intercellular edema and hemorrhage.1-3 …

Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller

Electronic Theses and Dissertations

Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations and Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …

Muc13 Enhances Colorectal Cancer Metastasis, Kyle Doxtater

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are …

Imaging Based Prediction Of Pathology In Adult Diffuse Glioma With Applications To Therapy And Prognosis, Evan Gates

Dissertations and Theses (Open Access)

The overall aggressiveness of a glioma is measured by histologic and molecular analysis of tissue samples. However, the well-known spatial heterogeneity in gliomas limits the ability for clinicians to use that information to make spatially specific treatment decisions. Magnetic resonance imaging (MRI) visualizes and assesses the tumor. But, the exact degree to which MRI correlates with the actual underlying tissue characteristics is not known.

In this work, we derive quantitative relationships between imaging and underlying pathology. These relations increase the value of MRI by allowing it to be a better surrogate for underlying pathology and they allow evaluation of the …

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

Patient-Reported Barriers Are Associated With Receipt Of Hepatocellular Carcinoma Surveillance In A Multicenter Cohort Of Patients With Cirrhosis, Amit G Singal, Jasmin A Tiro, Caitlin C Murphy, James-Michael Blackwell, Jennifer R Kramer, Aisha Khan, Yan Liu, Song Zhang, Jessica L Phillips, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt.

METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration.

RESULTS: Of 2871 patients …

Non-Selective Primary Human Tumor Cell Line Generation From Surgical Resections To Be Paired With Flash Frozen And Paraffin Embedded Tissue: Advancements In Democratizing Translational Research Materials To Rural Institutions, Jennifer Hawkins, Rebecca Russell, Logan M. Lawrence, Amrita Valluri, Jessica Wellman, Krista Denning

Marshall Journal of Medicine

Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer research samples. Biorepositories routinely supply researchers with varying sample types for use in biomedical studies; most commonly formalin-fixed and paraffin-embedded (FFPE) tissue, or fresh snap-frozen tissue. In conjunction with preserved tissue samples, viable tumor cell lines derived from patient tissue have emerged to be a new gold standard in cancer research particularly in drug discovery and functional prognostic assays. Tissue banks providing these samples are …

C17: Programmed Cell Death Ligand- 1 Expression As A Prognostic Indicator In Oral Squamous Cell Carcinoma, Dr. Samar Saeed Khan

Annual Research Symposium

No abstract provided.

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) …

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 …

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 …

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 …

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 …

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 …