Ultrahigh Resolution Lipid Mass Spectrometry Imaging Of High-Grade Serous Ovarian Cancer Mouse Models, Xin Ma, Andro Botros, Sylvia R Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M Matzuk, Jaeyeon Kim, Facundo M Fernández

Faculty, Staff and Students Publications

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n …

Clinical Significance Of Glycolytic Metabolic Activity In Hepatocellular Carcinoma, Joann Jung, Sowon Park, Yeonwoo Jang, Sung-Hwan Lee, Yun Seong Jeong, Sun Young Yim, Ju-Seog Lee

Faculty, Staff and Student Publications

High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor …

The Diagnostic Performance Of Ultrasonography In The Evaluation Of Extrathyroidal Extension In Papillary Thyroid Carcinoma: A Systematic Review And Meta-Analysis, Peter P. Issa, Aaron L. Albuck, Eslam Hossam, Mohammad Hussein, Mohamed Aboueisha, Abdallah S. Attia, Mahmoud Omar, Seif Abdelrahman, Gehad Naser, Robert D.E. Clark, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74–78%). The …

Anti-Cancer Mechanisms Of Action Of Therapeutic Alternating Electric Fields (Tumor Treating Fields [Ttfields]), Shadi Shams, Chirag B Patel

Faculty, Staff and Student Publications

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many …

Concurrent Mutations In Sf3b1 And Phf6 In Myeloid Neoplasms, Zhuang Zuo, L Jeffrey Medeiros, Sofia Garces, Mark J Routbort, Chi Young Ok, Sanam Loghavi, Rashmi Kanagal-Shamanna, Fatima Zahra Jelloul, Guillermo Garcia-Manero, Kelly S Chien, Keyur P Patel, Rajyalakshmi Luthra, C Cameron Yin

Faculty, Staff and Student Publications

It has been reported that gene mutations in SF3B1 and PHF6 are mutually exclusive. However, this observation has never been rigorously assessed. We report the clinicopathologic and molecular genetic features of 21 cases of myeloid neoplasms with double mutations in SF3B1 and PHF6, including 9 (43%) with myelodysplastic syndrome, 5 (24%) with acute myeloid leukemia, 4 (19%) with myeloproliferative neoplasms, and 3 (14%) with myelodysplastic/myeloproliferative neoplasms. Multilineage dysplasia with ring sideroblasts, increased blasts, and myelofibrosis are common morphologic findings. All cases but one had diploid or non-complex karyotypes. SF3B1 mutations were detected in the first analysis of all the …

Stabilization Of Mcl-1 By E3 Ligase Traf4 Confers Radioresistance, Ming Li, Feng Gao, Xiaoying Li, Yu Gan, Shuangze Han, Xinfang Yu, Haidan Liu, Wei Li

Faculty, Staff and Students Publications

The E3 ligase TNF receptor-associated factor 4 (TRAF4) is frequently overexpressed and closely related to poor prognosis in human malignancies. However, its effect on carcinogenesis and radiosensitivity in oral squamous cell carcinoma (OSCC) remains unclear. The present study found that TRAF4 was significantly upregulated in primary and relapsed OSCC tumor tissues. Depletion of TRAF4 markedly improved the sensitivity of OSCC cells to irradiation (IR) treatment, showing that tumor cell proliferation, colony formation and xenograft tumor growth were reduced. Mechanistically, IR promoted the interaction between TRAF4 and Akt to induce Akt K63-mediated ubiquitination and activation. TRAF4 knockout inhibited the phosphorylation of …

Nurse-Led Education On Oral Chemotherapy Medications, Carmen Lucia Glick Alonso

Master's Projects and Capstones

Problem: Breast cancer is one of the leading causes of cancer death among women in the United States. Annually, around 264,000 breast cancer cases are diagnosed in women and 2,400 in men (Centers for Disease Control and Prevention, 2022). According to the American Cancer Society, the risk of a woman in the United States being diagnosed with breast cancer in their life is around 13% (2022).

Context: Along with a cancer diagnosis comes the need to introduce patient education about new oral chemotherapy treatments. As a treatment team member, the oncology nurse plays a vital role in this …

An Imaging Mass Spectrometry Investigation Into The N-Linked Glycosylation Landscape Of Pancreatic Ductal Adenocarcinoma And The Development Of Associated Tools For Enhanced Glycan Separation And Characterization, Colin Mcdowell

MUSC Theses and Dissertations

The severity of pancreatic ductal adenocarcinoma (PDAC) is largely attributed to a failure to detect the disease before metastatic spread has occurred. CA19-9, a carbohydrate biomarker, is used clinically to surveille disease progression, but due to specificity challenges is not suitable for early discovery. As CA19-9 and other prospective markers are glycan epitopes, there is great clinical interest in understanding the glycobiology of pancreatic cancer. Unfortunately, few studies have been able to link glycosylation changes directly to pancreatic tumors and instead have focused on peripheral glycan alterations in the serum of PDAC patients. To address this gap in our understanding, …

A Path To Translation: How 3d Patient Tumor Avatars Enable Next Generation Precision Oncology, Shree Bose, Margarida Barroso, Milan G Chheda, Hans Clevers, Elena Elez, Salma Kaochar, Scott E Kopetz, Xiao-Nan Li, Funda Meric-Bernstam, Clifford A Meyer, Haiwei Mou, Kristen M Naegle, Martin F Pera, Zinaida Perova, Katerina A Politi, Benjamin J Raphael, Paul Robson, Rosalie C Sears, Josep Tabernero, David A Tuveson, Alana L Welm, Bryan E Welm, Christopher D Willey, Konstantin Salnikow, Jeffrey H Chuang, Xiling Shen

Faculty, Staff and Students Publications

3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require standardization criteria and prospective trials to establish clinical benefits. Innovative trial designs that combine omics and 3D-PTA readouts may lead to more accurate clinical predictors, and an integrated platform that combines diagnostic and therapeutic development will accelerate new treatments for patients with refractory disease.

Distance To Radiation Therapy Facility Influences Surgery Type Among Older Women With Early-Stage Breast Cancer, Pratibha Shrestha, Quyen D. Chu, Mei Chin Hsieh, Yong Yi, Edward S. Peters, Edward Trapido, Qingzhao Yu, Tekeda Ferguson, Xiao-Cheng Wu

School of Public Health Faculty Publications

Background: Breast-conserving surgery plus radiation (BCT) yields equivalent or better survival than mastectomy for early-stage breast cancer (ESBC) women. However, nationwide mastectomy trends increased in recent decades, attracting studies on underlying causes. Prior research identified that long distance to the radiation treatment facility (RTF) was associated with mastectomy. Still, it is unclear whether such association applies to young and old ESBC women comparably. We sought to delineate such impacts by age. Methods: Women diagnosed with stages 0–II breast cancer in 2013–2017 receiving either BCT or mastectomy were identified from the Louisiana Tumor Registry. We assessed the association of surgery (mastectomy …

Lpa Disruption With Aav-Crispr Potently Lowers Plasma Apo(A) In Transgenic Mouse Model: A Proof-Of-Concept Study, Alexandria M Doerfler, So Hyun Park, Julia M Assini, Amer Youssef, Lavanya Saxena, Adam B Yaseen, Marco De Giorgi, Marcel Chuecos, Ayrea E Hurley, Ang Li, Santica M Marcovina, Gang Bao, Michael B Boffa, Marlys L Koschinsky, William R Lagor

Faculty, Staff and Students Publications

Lipoprotein(a) (Lp(a)) represents a unique subclass of circulating lipoprotein particles and consists of an apolipoprotein(a) (apo(a)) molecule covalently bound to apolipoprotein B-100. The metabolism of Lp(a) particles is distinct from that of low-density lipoprotein (LDL) cholesterol, and currently approved lipid-lowering drugs do not provide substantial reductions in Lp(a), a causal risk factor for cardiovascular disease. Somatic genome editing has the potential to be a one-time therapy for individuals with extremely high Lp(a). We generated an

Indwelling Pleural Catheterization Maximizes Functionality And Quality Of Life In Management Of Recurrent Malignant Pleural Effusions, Avinash Ramkissoon

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: The TIME2 randomized controlled trial. J Am Med Assoc. 2012;307(22):2383-2389. https://doi.org/10.1001/jama.2012.5535

for the management of recurrent malignant pleural effusions in a patient with metastatic renal cell carcinoma.

A Cross-Sectional Study Of The Prevalence Of Anal Dysplasia Among Women With High-Grade Cervical, Vaginal, And Vulvar Dysplasia Or Cancer: The Panda Study, Samantha Batman, Craig A Messick, Andrea Milbourne, Ming Guo, Mark F Munsell, Joel Fokom-Domgue, Mila Salcedo, Ashish Deshmukh, Kristina R Dahlstrom, Mallory Ogburn, Anthony Price, Nicole D Fleming, Jolyn Taylor, Aaron Shafer, Lauren Cobb, Keith Sigel, Erich M Sturgis, Elizabeth Y Chiao, Kathleen M Schmeler

Faculty, Staff and Students Publications

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women.

METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA).

RESULTS: 324 evaluable women were enrolled. …

Survival Analysis And Prognostic Factors Of The Carcinoma Of Gallbladder, Zainab Feroz, Priyanka Gautam, Sonia Tiwari, Girish C. Shukla, Munish Kuma

Biological, Geological, and Environmental Faculty Publications

Background: The present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions.
Methods: The study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method.
Results: The overall median survival time of patients was 5 months with the 1-year, …

Rapid Detection Of Recurrent Non-Muscle Invasive Bladder Cancer In Urine Using Atr-Ftir Technology, Abdullah I. El-Falouji, Dalia M. Sabri, Naira M. Lofti, Doaa M. Medany, Samar A. Mohamed, Mai Alaa-Eldin, Amr Mounir Selim, Asmaa A. El Leithy, Haitham F. Kalil, Ahmed El-Tobgy, Ahmed Mohamed

Chemistry Faculty Publications

Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) …

Data-Driven Biomarker Panel Discovery In Ovarian Cancer Using Heterogenous Data Fusion On Exosomal And Non-Exosomal Microrna Expression Data, Paritra Mandal

All Dissertations

Ovarian cancer (OC) is an aggressive gynecological cancer and is currently the 5th leading cause of deaths due to cancer in women. High mortality rates are attributable to the vague pathogenesis and asymptomatic nature of the early stages. The development of a liquid biopsy for routine OC screening could help identify the disease at an earlier stage, making treatments more likely to be effective thereby increasing survival rates. Exosomes, small (~100nm) extracellular vesicles present in body fluids, have been shown to contain cancer-progression, onset, and related factors, making them good candidates for use in liquid biopsies. However, to date, only …

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

Graduate Theses and Dissertations (2019 - present)

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Genomic Profiling For Clinical Decision Making In Myeloid Neoplasms And Acute Leukemia, Eric J Duncavage, Adam Bagg, Robert P Hasserjian, Courtney D Dinardo, Lucy A Godley, Ilaria Iacobucci, Siddhartha Jaiswal, Luca Malcovati, Alessandro M Vannucchi, Keyur P Patel, Daniel A Arber, Maria E Arcila, Rafael Bejar, Nancy Berliner, Michael J Borowitz, Susan Branford, Anna L Brown, Catherine A Cargo, Hartmut Döhner, Brunangelo Falini, Guillermo Garcia-Manero, Torsten Haferlach, Eva Hellström-Lindberg, Annette S Kim, Jeffery M Klco, Rami Komrokji, Mignon Lee-Cheun Loh, Sanam Loghavi, Charles G Mullighan, Seishi Ogawa, Attilio Orazi, Elli Papaemmanuil, Andreas Reiter, David M Ross, Michael Savona, Akiko Shimamura, Radek C Skoda, Francesc Solé, Richard M Stone, Ayalew Tefferi, Matthew J Walter, David Wu, Benjamin L Ebert, Mario Cazzola

Faculty, Staff and Student Publications

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome …

Clinicopathological And Prognostic Significance Of Cxcr4 Expression In Osteosarcoma: A Meta-Analysis, I Gusti Ngurah Ananda Wira Kusuma, Grace Yulia Alphani Yapson, John Nolan, I Gede Eka Wiratnaya, I Gede Putu Supadmanaba

BioMedicine

Background: The C-X-C Motif Chemokine Receptor (CXCR4) is an oncogene that has been widely studied and associated with worse clinicopathological features and prognosis outcomes in many types of cancer. Besides that, significance of CXCR4 expression on clinicopathological features and prognostic factors in osteosarcoma (OS) requires further validation.

Aim: We conducted a meta-analysis to evaluate the association between positive CXCR4 expression with clinicopathological features and prognosis in OS.

Methods: Literature searches on Pubmed, Cochrane Library, and Web of Science were conducted systematically up to December 2021 to find relevant references. The effects of CXCR4 expression on clinicopathological characteristics and prognostic were …

Preclinical Evaluation Of Combination Nemtabrutinib And Venetoclax In Chronic Lymphocytic Leukemia, Elizabeth M Muhowski, Janani Ravikrishnan, Britten Gordon, Lianbo Yu, Shrilekha Misra, Brandi Walker, Sudharshan Eathiraj, Deepa Sampath, Kerry A Rogers, John C Byrd, Jennifer A Woyach

Faculty, Staff and Student Publications

Inhibitors of B cell receptor (BCR) signaling such as the Bruton's tyrosine kinase (BTK) inhibitors are effective therapeutics for chronic lymphocytic leukemia (CLL). The first-in-class covalent BTK inhibitor, ibrutinib, produces durable responses in most CLL patients; however, complete responses are only observed in a minority of patients. B cell lymphoma 2 (BCL2), an anti-apoptotic protein that contributes to CLL cell survival, has also been investigated as a therapeutic target. The BCL2 inhibitor venetoclax is effective in patients with CLL and can produce undetectable minimal residual disease, allowing discontinuation of therapy. In combination, ibrutinib and venetoclax have shown preclinical synergy and …

Erk Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro And In Vivo, Yang Yu, Yanling Zhao, Jongmin Choi, Zhongcheng Shi, Linjie Guo, John Elizarraras, Andy Gu, Feng Cheng, Yanxin Pei, Dai Lu, Muller Fabbri, Saurabh Agarwal, Chunchao Zhang, Sung Yun Jung, Jennifer H Foster, Jianhua Yang

Faculty, Staff and Students Publications

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed …

Metabolic Pathways Enriched According To Erg Status Are Associated With Biochemical Recurrence In Hispanic/Latino Patients With Prostate Cancer, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Melody C. Baddoo, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Marcela Nuñez Lemus, Martha Lucía Serrano, Jovanny Zabaleta, Alba L. Combita, María Carolina Sanabria-Salas

School of Medicine Faculty Publications

Background: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed …

Dll3 As An Emerging Target For The Treatment Of Neuroendocrine Neoplasms, James Yao, Emily Bergsland, Rahul Aggarwal, Ana Aparicio, Himisha Beltran, Judy S Crabtree, Christine L Hann, Toni Ibrahim, Lauren A Byers, Hironobu Sasano, John Umejiego, Marianne Pavel

Faculty, Staff and Student Publications

INTRODUCTION: Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis.

METHODS: This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lag-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

Outcomes Of Gynecologic Cancer Surgery During The Covid-19 Pandemic: An International, Multicenter, Prospective Covidsurg-Gynecologic Oncology Cancer Study, Christina Fotopoulou, Tabassum Khan, Juraj Bracinik, James Glasbey, Nadeem Abu-Rustum, Luis Chiva, Anna Fagotti, Keiichi Fujiwara, Rahel Ghebre, Murat Gutelkin, Thomas O Konney, Joseph Ng, Rene Pareja, Rajkumar Kottayasamy Seenivasagam, Jalid Sehouli, Shylasree T S Surappa, Aneel Bhangu, Elaine Leung, Sudha Sundar

Faculty, Staff and Student Publications

BACKGROUND: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear.

OBJECTIVE: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive …