Medical Specialties Commons^™

Sensei: How Many Samples To Tell A Change In Cell Type Abundance?, Shaoheng Liang, Jason Willis, Jinzhuang Dou, Vakul Mohanty, Yuefan Huang, Eduardo Vilar, Ken Chen

Faculty, Staff and Student Publications

Cellular heterogeneity underlies cancer evolution and metastasis. Advances in single-cell technologies such as single-cell RNA sequencing and mass cytometry have enabled interrogation of cell type-specific expression profiles and abundance across heterogeneous cancer samples obtained from clinical trials and preclinical studies. However, challenges remain in determining sample sizes needed for ascertaining changes in cell type abundances in a controlled study. To address this statistical challenge, we have developed a new approach, named Sensei, to determine the number of samples and the number of cells that are required to ascertain such changes between two groups of samples in single-cell studies. Sensei expands …

Transcranial Stimulation Of Alpha Oscillations Up-Regulates The Default Mode Network, Kevin J Clancy, Jeremy A Andrzejewski, Yuqi You, Jens T Rosenberg, Mingzhou Ding, Wen Li

Faculty, Staff and Student Publications

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, …

Intrapulmonary Teratoma: A Rare Presentation Of Bronchiectasis, Beren Chandler, Garret Duron, Jason Mcclune, Lindsey Goldberg

South Atlantic Division GME Research Day 2022

No abstract provided.

Not Just An Accident: A Case Of Insulinoma, Asanka Ekanayake, Harrison Stubbs, Dominique Broutin, Olga Karasik, Mustafa Kinaan

North Florida Division GME Research Day 2022

No abstract available.

Implementing Nih Behavior Change Consortium Treatment Fidelity Recommendations In A Multi-Site Randomized Controlled Trial Of An Active Music Engagement Intervention For Young Children With Cancer And Parents., Jessica A. Maclean, Kristin Stegenga, Amanda K. Henley, Sheri L. Robb

Manuscripts, Articles, Book Chapters and Other Papers

Treatment fidelity is the use of methodological strategies to monitor and enhance reliability and validity of behavioral intervention trials. Despite availability of guidelines and checklists, treatment fidelity remains underreported, hindering evaluation, interpretation, and cross-study comparisons. Treatment fidelity is particularly important for music interventions given the inherent complexity of musical stimuli and flexibility required for tailored delivery. The purpose of this paper is to define and describe treatment fidelity strategies for our trial of a music-based play intervention for young children with cancer and parents grounded in the NIH Behavior Change Consortium Treatment Fidelity Recommendations. We report strategies for all 5 …

In Utero Exposure To 17Α-Hydroxyprogesterone Caproate And Risk Of Cancer In Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: 17α-hydroxyprogesterone caproate is a synthetic progestogen initially approved in the 1950s to treat gynecologic and obstetrical conditions. Despite continued concerns about safety and short-term efficacy regarding the use of 17α-hydroxyprogesterone caproate for the prevention of preterm birth in pregnant women, little is known about the long-term effects of 17α-hydroxyprogesterone caproate on the health of the offsprings.

OBJECTIVE: To examine the association between in utero exposure to 17α-hydroxyprogesterone caproate and the risk of cancer in the offspring.

STUDY DESIGN: The Child Health and Development Studies was a population-based cohort of >18,000 mother-child dyads receiving prenatal care in the Kaiser Foundation …

Surgical Intervention For Phlegmasia Cerulea Dolens In A 61-Year-Old Cancer Patient, Christopher Ruben-Castillo, Cesar Cuen-Ojeda, Gabriel Lopez-Peña, Javier E Anaya-Ayala, Carlos A Hinojosa

The Texas Heart Institute Journal

Phlegmasia cerulea dolens, a rare and potentially fatal complication of acute deep vein thrombosis, is characterized by substantial edema, intense pain, and cyanosis. Phlegmasia cerulea dolens may compromise limb perfusion and lead to acute ischemia, gangrene, amputation, and death. We present the case of a 61-year-old woman with a history of breast cancer who had signs and symptoms of phlegmasia cerulea dolens in her left leg. She was treated promptly with open surgical thrombectomy and sequential distal compression with use of an Esmarch bandage to ensure complete thrombus extraction. These techniques restored venous flow and saved her leg. Open surgical …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

Multiplexed Engineering And Precision Gene Editing In Cellular Immunotherapy, Alexander Biederstädt, Gohar Shahwar Manzar, May Daher

Faculty, Staff and Student Publications

The advent of cellular immunotherapy in the clinic has entirely redrawn the treatment landscape for a growing number of human cancers. Genetically reprogrammed immune cells, including chimeric antigen receptor (CAR)-modified immune effector cells as well as T cell receptor (TCR) therapy, have demonstrated remarkable responses across different hard-to-treat patient populations. While these novel treatment options have had tremendous success in providing long-term remissions for a considerable fraction of treated patients, a number of challenges remain. Limited

Granuloma Annulare: An Updated Review Of Epidemiology, Pathogenesis, And Treatment Options, Tejas P Joshi, Madeleine Duvic

Faculty, Staff and Student Publications

Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized …

Editorial: The Role Of The Igf Axis In Tumorigenesis And Cancer Treatment: From Genes To Metabolites, Guo Mengzhe, Xie Shanshan, Zhao Di, Wu Shihua

Faculty, Staff and Student Publications

No abstract provided.

Cancer Prevention Behaviors In Workers Of A Referral Cancer Center In Mexico City: A Pilot Study On Early Detection Awareness For Cancer, Nancy Reynoso-Noverón, Shine Chang, Luis Alonso Herrera-Montalvo, Abelardo Meneses-García

Faculty, Staff and Student Publications

Background: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City.

Methods: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated …

Recurrent High-Impact Mutations At Cognate Structural Positions In Class A G Protein-Coupled Receptors Expressed In Tumors, Eunna Huh, Jonathan Gallion, Melina A Agosto, Sara J Wright, Theodore G Wensel, Olivier Lichtarge

Faculty, Staff and Students Publications

G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer. Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling similarly so as to favor a tumor. We hypothesized that somatic mutations in tumor samples may not be enriched within a single gene but rather that cognate mutations with similar effects on GPCR function are distributed across many receptors. To test this possibility, we systematically aggregated …

Induction Of Hypopituitarism Following Ipilimumab/ Nivolumab Therapy Followed By Radiation In The Treatment Of Metastatic Scalp Melanoma, Joshua K. Salabei, Dhaval Upadhyay, Sripal A. Padam

HCA Healthcare Journal of Medicine

Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to …

Replication Stress Response Defects Are Associated With Response To Immune Checkpoint Blockade In Nonhypermutated Cancers, Daniel J Mcgrail, Patrick G Pilié, Hui Dai, Truong Nguyen Anh Lam, Yulong Liang, Leonie Voorwerk, Marleen Kok, Xiang H-F Zhang, Jeffrey M Rosen, Amy B Heimberger, Christine B Peterson, Eric Jonasch, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Treatment with immune checkpoint blockade (ICB) has resulted in durable responses for a subset of patients with cancer, with predictive biomarkers for ICB response originally identified largely in the context of hypermutated cancers. Although recent clinical data have demonstrated clinical responses to ICB in certain patients with nonhypermutated cancers, previously established ICB response biomarkers have failed to accurately identify which of these patients may benefit from ICB. Here, we demonstrated that a replication stress response (RSR) defect gene expression signature, but not other proposed biomarkers, is associated with ICB response in 12 independent cohorts of patients with nonhypermutated cancer across …

Invariant Natural Killer T-Cell Subsets Have Diverse Graft-Versus-Host-Disease-Preventing And Antitumor Effects, Kristina Maas-Bauer, Juliane K Lohmeyer, Toshihito Hirai, Teresa Lopes Ramos, Furqan M Fazal, Ulrike M Litzenburger, Kathryn E Yost, Jessica V Ribado, Neeraja Kambham, Arielle S Wenokur, Po-Yu Lin, Maite Alvarez, Melissa Mavers, Jeanette Baker, Ami S Bhatt, Howard Y Chang, Federico Simonetta, Robert S Negrin

Faculty, Staff and Students Publications

Invariant natural killer T (iNKT) cells are a T-cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic graft-versus-host-disease (GVHD). Murine iNKT cells differentiate during thymic development into iNKT1, iNKT2, and iNKT17 sublineages, which differ transcriptomically and epigenomically and have subset-specific developmental requirements. Whether distinct iNKT sublineages also differ in their antitumor effect and their ability to suppress GVHD is currently unknown. In this work, we generated highly purified murine iNKT sublineages, characterized their transcriptomic and epigenomic landscape, …

The Concurrence Of Dna Methylation And Demethylation Is Associated With Transcription Regulation, Jiejun Shi, Jianfeng Xu, Yiling Elaine Chen, Jason Sheng Li, Ya Cui, Lanlan Shen, Jingyi Jessica Li, Wei Li

Children’s Nutrition Research Center Staff Publications

The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been intensively studied in the past decade, the direct effects of their interaction on gene expression remain elusive. Here, we quantify the concurrence of DNA methylation and demethylation by the percentage of unmethylated CpGs within a partially methylated read from bisulfite sequencing. After verifying 'methylation concurrence' by its strong association with the co-localization of DNMT and TET enzymes, we observe that methylation concurrence is strongly correlated with gene expression. …

Genomic Data From Nsclc Tumors Reveals Correlation Between Shp-2 Activity And Pd-L1 Expression And Suggests Synergy In Combining Shp-2 And Pd-1/Pd-L1 Inhibitors, Keller J. Toral, Mark A. Wuenschel, Esther P. Black

Pharmaceutical Sciences Faculty Publications

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition …

Returning To Sport: Female Athletes Living With And Beyond Cancer., Anna L. Schwartz, Christopher Terry

Kimmel Cancer Center Faculty Papers

Many athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to the lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer …

Digital Literacy At An Urban Cancer Center: Implications For Technology Use And Vulnerable Patients, Amy Leader, Lisa M. Capparella, L. Waldman, Ba, Rebecca Cammy, Alison Petok, Rebecca Dean, Ayako Shimada, Liana Yocavitch, Kristin L. Rising, Gregory Garber, Brooke Worster, Adam Dicker

Kimmel Cancer Center Faculty Papers

PURPOSE: eHealth literacy, or the ability to seek, find, understand, and appraise health information from electronic sources, has become increasingly relevant in the era of COVID-19, when so many aspects of patient care became dependent on technology. We aimed to understand eHealth literacy among a diverse sample of patients with cancer and discuss ways for health systems and cancer centers to ensure that all patients have access to high-quality care.

METHODS: A cross-sectional survey of patients with cancer and caregivers was conducted at an NCI-designated cancer center to assess access to the Internet, smartphone ownership, use of mobile apps, willingness …

The Detrimental Association Between Fear Of Falling And Motor Performance In Older Cancer Patients With Chemotherapy-Induced Peripheral Neuropathy, Gu Eon Kang, Tamiko K Murphy, Mark E Kunik, Hoda J Badr, Biruh T Workeneh, Sarvari V Yellapragada, Yvonne H Sada, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN.

RESEARCH QUESTION: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits?

METHODS: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with …

Two Mechanisms Of Chromosome Fragility At Replication-Termination Sites In Bacteria, Qian Mei, Devon M Fitzgerald, Jingjing Liu, Jun Xia, John P Pribis, Yin Zhai, Ralf B Nehring, Jacob Paiano, Heyuan Li, Andre Nussenzweig, P J Hastings, Susan M Rosenberg

Faculty, Staff and Students Publications

Chromosomal fragile sites are implicated in promoting genome instability, which drives cancers and neurological diseases. Yet, the causes and mechanisms of chromosome fragility remain speculative. Here, we identify three spontaneous fragile sites in the Escherichia coli genome and define their DNA damage and repair intermediates at high resolution. We find that all three sites, all in the region of replication termination, display recurrent four-way DNA or Holliday junctions (HJs) and recurrent DNA breaks. Homology-directed double-strand break repair generates the recurrent HJs at all of these sites; however, distinct mechanisms of DNA breakage are implicated: replication fork collapse at natural replication …

Phyllodes Tumor Containing Invasive Ductal Carcinoma: A Rare Case Description & Review Of Literature, Kathryn Eckert, John Ground, Alyssa Imperatore, Victoria Tiedemann, Linda Szczurek

Rowan-Virtua Research Day

Phyllodes tumors are uncommon, often benign, malignancies of the breast and account for approximately 0.5% of all breast malignancies. These tumors were first described in 1838 by Johannes Muller as cystosarcoma phyllodes and were later more aptly renamed phyllodes tumors (as they were neither cystic nor sarcomatous).(1) As a mixed connective tissue and epithelial tumor, these behave similar to benign fibroadenomas, though their growth is much more rapid and they tend to occur in older patients.(2) Hallmarked by their large size at presentation, these tumors average between 4 and 7 cm at the time of diagnosis. The only known risk …

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 …

Diabetes In The Oncology Setting Webinar Series, Jennifer Williams, Denise A. Palma, Michael Rizk Msn, Aprn, Fnp-C, Bc-Adm

Education Week Poster Showcase 2021

Department of Endocrine Neoplasia and Hormonal Disorders

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) …

Is Covid-19-Induced Platelet Activation A Cause Of Concern For Patients With Cancer?, Lenard M Lichtenberger, K Vinod Vijayan

Faculty, Staff and Students Publications

Patients with cancer are more susceptible to be infected by SARS-CoV-2 and develop severe outcomes including ICU admittance, mechanical ventilator support, and a high rate of mortality. Like mid-to late-stage cancer, SARS-CoV-2 infection is associated with platelet hyperactivity, systemic inflammation, thrombotic complications, and coagulopathy. Platelets also promote cancer cell growth, survival in circulation, and angiogenesis at sites of metastases. In this article, we will discuss the potential for platelets in the development of systemic inflammation and thrombosis in SARS-CoV-2-infected patients with cancer, with the concern that the platelet-induced pathogenic events are likely magnified in cancer patients with COVID-19.

Conservation Of Epithelial-To-Mesenchymal Transition Process In Neural Crest Cells And Metastatic Cancer, April Zhang, Hira Aslam, Neha Sharma, Aryeh Warmflash, Walid D Fakhouri

Faculty, Staff and Student Publications

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis …