Medical Specialties Commons^™

Effectiveness Of Skill‑Building Interventions For Informal Caregivers Of Adults With Cancer: A Systematic Review, M. Courtney Hughes, Sadia Afrin, Tamara Hamlish

Faculty Articles, Papers, and Other Scholarship

Over 19 million people worldwide were diagnosed with cancer in 2020. Informal caregivers of adults with cancer play an important role in helping their loved ones with cancer yet often receive little support in developing the necessary skills for caregiving. A systematic review of skill-building interventions for informal caregivers of adults with cancer was conducted across three electronic databases for academic articles published through February 2022. PRISMA reporting guidelines were followed throughout this review, the Mixed Methods Appraisal Tool was used to assess study quality, and results were summarized in a narrative synthesis. The main components of skill-building interventions examined …

Medicc2: Whole-Genome Doubling Aware Copy-Number Phylogenies For Cancer Evolution, Tom L Kaufmann, Marina Petkovic, Thomas B K Watkins, Emma C Colliver, Sofya Laskina, Nisha Thapa, Darlan C Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi, Roland F Schwarz

Faculty, Staff and Student Publications

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.

Tumor Suppressor Dear1 Regulates Mammary Epithelial Cell Fate And Predicts Early Onset And Metastasis In Triple Negative Breast Cancer, Uyen Q Le, Nanyue Chen, Seetharaman Balasenthil, Eugene Lurie, Fei Yang, Suyu Liu, Laura Rubin, Luisa Maren Solis Soto, Maria Gabriela Raso, Harsh Batra, Aysegul A Sahin, Ignacio I Wistuba, Ann Mcneill Killary

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are …

Challenges Associated With The Integration Of Immuno-Oncology Agents In Clinical Practice, Patrice Lazure, Aparna R Parikh, Neal E Ready, Marianne J Davies, Sophie Péloquin, Jeffrey M Caterino, Robert Lewandowski, Alexander J Lazar, Suzanne Murray

Faculty, Staff and Student Publications

Background: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents.

Methods: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali

Department of Pathology and Laboratory Medicine

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …

Targeting The Mdm2-P53 Pathway In Dedifferentiated Liposarcoma, Raymond S Traweek, Brandon M Cope, Christina L Roland, Emily Z Keung, Elise F Nassif, Derek J Erstad

Faculty, Staff and Student Publications

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered …

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 …

Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Faculty, Staff and Student Publications

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The …

Multi-Organ Segmentation Of Abdominal Structures From Non-Contrast And Contrast Enhanced Ct Images, Cenji Yu, Chidinma P Anakwenze, Yao Zhao, Rachael M Martin, Ethan B Ludmir, Joshua S Niedzielski, Asad Qureshi, Prajnan Das, Emma B Holliday, Ann C Raldow, Callistus M Nguyen, Raymond P Mumme, Tucker J Netherton, Dong Joo Rhee, Skylar S Gay, Jinzhong Yang, Laurence E Court, Carlos E Cardenas

Faculty, Staff and Student Publications

Manually delineating upper abdominal organs at risk (OARs) is a time-consuming task. To develop a deep-learning-based tool for accurate and robust auto-segmentation of these OARs, forty pancreatic cancer patients with contrast-enhanced breath-hold computed tomographic (CT) images were selected. We trained a three-dimensional (3D) U-Net ensemble that automatically segments all organ contours concurrently with the self-configuring nnU-Net framework. Our tool's performance was assessed on a held-out test set of 30 patients quantitatively. Five radiation oncologists from three different institutions assessed the performance of the tool using a 5-point Likert scale on an additional 75 randomly selected test patients. The mean (± …

Experiences Of Participants In A Clinical Trial Of A Novel Radioactive Treatment For Advanced Prostate Cancer: A Nested, Qualitative Longitudinal Study, Bianca Viljoen, Michael S. Hofman, Suzanne K. Chambers, Jeff Dunn, Haryana M. Dhillon, Ian D. Davis, Nicholas Ralph

Research outputs 2022 to 2026

Objectives: Qualitative studies nested within clinical trials can provide insight into the treatment experience, how this evolves over time and where improved supportive care is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy. Methods: Fifteen men with advanced prostate cancer were recruited from the TheraP clinical trial with interviews conducted at three timepoints during the trial. An interpretative phenomenological approach was used, and interviews analysed using thematic analysis. This research paper reports the results from …

Conducting A Supportive Oncology Clinical Trial During The Covid-19 Pandemic: Challenges And Strategies, Jie Deng, John N. Lukens, Joy C. Cohn, Erin Mcmenamin, Barbara Murphy, Bryan A. Spinelli, Niya Murphy, Alicia K. Steinmetz, Megan A. Landriau, Alexander Lin

Department of Physical Therapy Faculty Papers

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances.

Trial registration: ClinicalTrials.gov, a service of the US National Institute of …

Promotion Of A Synthetic Degradation Of Activated Stat6 By Parp-1 Inhibition: Roles Of Poly(Adp-Ribosyl)Ation, Calpains And Autophagy, Jeffrey Wang, Mohamed A. Ghonim, Salome V. Ibba, Hanh H. Luu, Yucel Aydin, Peter A. Greer, A. Hamid Boulares

School of Medicine Faculty Publications

Background: We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods: This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results: We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes …

Body Mass Index And Survival After Cancer Diagnosis: A Pan-Cancer Cohort Study Of 114 430 Patients With Cancer, Huakang Tu, Jennifer L Mcquade, Michael A Davies, Maosheng Huang, Kunlin Xie, Yuanqing Ye, Wong-Ho Chow, Alma Rodriguez, Xifeng Wu

Faculty, Staff and Student Publications

The recommendation encouraging patients with cancer to keep a normal body mass index (BMI) is largely extrapolated from data on risk of developing cancer. We tested the prospective association between peri-diagnostic (within 1 year post-diagnosis) BMI and all-cause mortality in patients with incident cancers. During 7.2 years of follow-up, 42% (48,340) of the 114 430 patients with cancer died. Spline analysis revealed that compared with a BMI of 22.5, a BMI lower than 22.5 was associated with increased risk of all-cause mortality across 24 cancer types. A BMI higher than 22.5 was associated with reduced all-cause mortality, while a non-linear …

Omics Analyses Of A Somatic Trp53r245w/+ Breast Cancer Model Identify Cooperating Driver Events Activating Pi3k/Akt/Mtor Signaling, Xiaojie Yu, Yun Zhang, Shunbin Xiong, Joy M Mcdaniel, Chang Sun, Gilda P Chau, Jovanka Gencel-Augusto, Dhruv Chachad, Rhiannon L Morrissey, Xiayu Rao, Jing Wang, Guillermina Lozano

Faculty, Staff and Student Publications

Alterations of the tumor suppressor

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

A Randomized Pilot Study Of Oncology Massage To Treat Chemotherapy-Induced Peripheral Neuropathy, Gabriel Lopez, Cathy Eng, Michael Overman, David Ramirez, Wenli Liu, Curtiss Beinhorn, Pamela Sumler, Sarah Prinsloo, Yisheng Li, Minxing Chen, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0-10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

Polygenic Risk Score Improves The Accuracy Of A Clinical Risk Score For Coronary Artery Disease, Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Faculty, Staff and Student Publications

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine …

Blockade Of Fgf2/Fgfr2 Partially Overcomes Bone Marrow Mesenchymal Stromal Cells Mediated Progression Of T-Cell Acute Lymphoblastic Leukaemia, Chen Tian, Yueyang Li, Lina Wang, Junqi Si, Yaxin Zheng, Junnan Kang, Yafei Wang, M James You, Guoguang Zheng

Faculty, Staff and Student Publications

The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to find MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukaemic niche formation. RNA sequence results revealed that T-ALL derived MSCs secreted fibroblast growth factor 2 (FGF2), which …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

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 …

Metformin Increases Natural Killer Cell Functions In Head And Neck Squamous Cell Carcinoma Through Cxcl1 Inhibition, Mckenzie Crist, Benyamin Yaniv, Sarah Palackdharry, Maria A. Lehn, Mario Medvedovic, Timothy Stone, Shuchi Gulati, Vidhya Karivedu, Michael Borchers, Bethany Fuhrman, Audrey Crago, Joseph Curry, Ubaldo Martinez-Outschoorn, Vinita Takiar, Trisha M. Wise-Draper

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Metformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in our phase 1 clinical trial (NCT02325401). Metformin is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) and natural killer T cells, including results from two phase I open-label studies in patients with HNSCC treated with metformin (NCT02325401, NCT02083692).

METHODS: Peripheral blood was collected before and after metformin treatment or from newly diagnosed patients with HNSCC. Peripheral immune cell …

Characterization Of Bcma Expression In Circulating Rare Single Cells Of Patients With Plasma Cell Neoplasms, Libere J Ndacayisaba, Kate E Rappard, Stephanie N Shishido, Sonia M Setayesh, Guilin Tang, Pei Lin, Nicholas Matsumoto, Ching-Ju Hsu, Rafael Nevarez, Carmen Ruiz Velasco, Amin Naghdloo, Eric Yang, Kevin Kelly, James Hicks, Jeremy Mason, Robert Z Orlowski, Elisabet E Manasanch, Peter Kuhn

Faculty, Staff and Student Publications

B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients' blood could enable early disease profiling and therapy response monitoring. Here, we report …

Antibiotic Exposure Does Not Impact Immune Checkpoint Blockade Response In Msi-H/Dmmr Metastatic Colorectal Cancer: A Single-Center Experience, Victoria Serpas Higbie, Jane Rogers, Hyunsoo Hwang, Wei Qiao, Lianchun Xiao, Arvind Dasari, Kerri Mola-Rudd, Van K Morris, Robert A Wolff, Kanwal Raghav, Ryan Huey, Christine Parseghian, Jason Willis, Scott Kopetz, Michael J Overman, Benny Johnson

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has improved outcomes for patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors. However, not all MSI-H/dMMR patients will exhibit the same ICB efficacy. Previous studies suggest that concomitant antibiotic use while receiving ICB may result in poorer outcomes. We aimed to evaluate this association in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC).

MATERIALS AND METHODS: A single-site, retrospective review of 57 patients with MSI-H/dMMR mCRC that received ICB was completed. Data collected included patient demographics, ICB information, and antibiotic use. Antibiotic exposure was considered from 90 days prior to ICB through 6 weeks …

Sexual Dysfunction And Sexual Distress In Lymphoma Patients: A Mixed Methods Pilot Study, Dorothie S. Durosier Mertilus

USF Tampa Graduate Theses and Dissertations

Lymphoma, especially non-Hodgkin lymphoma (NHL), is among the most common categories of cancer in the United States (National Cancer Institute [NCI], 2019). The survival rate for lymphoma has significantly improved over the last few decades due to advances in therapy. However, despite these advances, lymphoma patients experience many negative consequences of cancer treatment, including sexual dysfunction (NCI, 2021b). The purpose of this mixed methods pilot study was to explore the presence and experiences of sexual dysfunction and related sexual distress in both male and female lymphoma patients during cancer treatment. A concurrent triangulated design was used to: 1) evaluate the …

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 …

Epacadostat Plus Pembrolizumab And Chemotherapy For Advanced Solid Tumors: Results From The Phase I/Ii Echo-207/Keynote-723 Study, John D Powderly, Samuel J Klempner, Aung Naing, Johanna Bendell, Ignacio Garrido-Laguna, Daniel V T Catenacci, Matthew H Taylor, James J Lee, Fred Zheng, Feng Zhou, Xiaohua Gong, Hema Gowda, Gregory L Beatty

Faculty, Staff and Student Publications

Background: Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

Methods: Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab …

Hormonal Therapies Up-Regulate Manf And Overcome Female Susceptibility To Immune Checkpoint Inhibitor Myocarditis, Yaohua Zhang, Chengcao Sun, Yajuan Li, Juan Qin, Kaushik Amancherla, Ying Jing, Qingsong Hu, Ke Liang, Zhao Zhang, Youqiong Ye, Lisa A Huang, Tina K Nguyen, Sergey D Egranov, Zilong Zhao, Andrew Wu, Yutao Xi, Jun Yao, Mien-Chie Hung, George A Calin, Jie Cheng, Bora Lim, Lorenz H Lehmann, Joe-Elie Salem, Douglas B Johnson, Michael A Curran, Dihua Yu, Leng Han, Radbod Darabi, Liuqing Yang, Javid J Moslehi, Chunru Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis …