Medicine and Health Sciences Commons^™

Meeting Highlights The 4th Marie Skłodowska-Curie Symposium On Cancer Research And Care: Mechanisms Of Support For Regional & International Collaborations, Pawel Kalinski, Kathleen M Kokolus, Indu Ahluwalia, Mihaela Balu, Łukasz Balwicki, Brygida Baran, Loretta Beine, Mikhail Berezin, Ioana Berindan-Neagoe, Andriy Beznosenko, Blanka Borowiec, Szabolcs Bozsányi, Jonathan Bramson, Brian Czerniecki, Rūta Everatt, Wojciech Fendler, Peter Forsyth, Jeffrey E Gershenwald, Maciej Goniewicz, Khurshid Guru, Andrew Hyland, Smitha James, Iva Kirac, Pawel Koczkodaj, Leszek Kotula, Maciej Łuba, Iwona Ługowska, Elizabeth Luke, Cristian Lungulescu, Sandro Matosevic, Kaushal Nanavati, Michael Nemeth, Karolina Nowak, Katia Noyes, Mark Parascandola, Waldemar Priebe, Piotr Rutkowski, Mukund Seshadri, Christine E Sheffer, Ioana-Miruna Stanciu, Joanna Stanson, Telisa Stewart, Edita Sužiedėlienė, Kęstutis Sužiedėlis, Iryna Tanasiichuk, Anda M Vlad, Wei-Zen Wei, Dylan Williams, Malgorzata Wojtowicz, Tomasz Zdrojewski

Faculty, Staff and Student Publications

The Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC) to accelerate the development of new cancer therapies, new strategies for early detection and prevention, and improve cancer care and the quality of life for patients and their families. The 4th MSCS-CRC (September 25-27, 2024, Buffalo, New York) brought together 147 participants from the US, Canada, Croatia, Czechia, Lithuania, Poland, Romania and Ukraine, and involved representatives of the US Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI) …

Comparison Of Deep Learning Schemes In Grading Non-Alcoholic Fatty Liver Disease Using B-Mode Ultrasound Hepatorenal Window Images With Liver Biopsy As The Gold Standard, Petros Drazinos, Ilias Gatos, Paraskevi F Katsakiori, Stavros Tsantis, Efstratios Syrmas, Stavros Spiliopoulos, Dimitris Karnabatidis, Ioannis Theotokas, Pavlos Zoumpoulis, John D Hazle, George C Kagadis

Faculty, Staff and Student Publications

Background/introduction: To evaluate the performance of pre-trained deep learning schemes (DLS) in hepatic steatosis (HS) grading of Non-Alcoholic Fatty Liver Disease (NAFLD) patients, using as input B-mode US images containing right kidney (RK) cortex and liver parenchyma (LP) areas indicated by an expert radiologist.

Methods: A total of 112 consecutively enrolled, biopsy-validated NAFLD patients underwent a regular abdominal B-mode US examination. For each patient, a radiologist obtained a B-mode US image containing RK cortex and LP and marked a point between the RK and LP, around which a window was automatically cropped. The cropped image dataset was augmented using up-sampling, …

Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos

Faculty, Staff and Student Publications

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson …

Safety And Activity Of Ctx130, A Cd70-Targeted Allogeneic Crispr-Cas9-Engineered Car T-Cell Therapy, In Patients With Relapsed Or Refractory T-Cell Malignancies (Cobalt-Lym): A Single-Arm, Open-Label, Phase 1, Dose-Escalation Study, Swaminathan P Iyer, R Alejandro Sica, P Joy Ho, Anca Prica, Jasmine Zain, Francine M Foss, Boyu Hu, Amer Beitinjaneh, Wen-Kai Weng, Youn H Kim, Michael S Khodadoust, Auris O Huen, Leah M Williams, Anna Ma, Elaine Huang, Avanti Ganpule, Shashwat Deepali Nagar, Parin Sripakdeevong, Erika L Cullingford, Sushant Karnik, Mary-Lee Dequeant, Janki N Patel, Xinyi Shirley He, Ziliang Li, Qiuling Ally He, Joy H Mendonez, Alissa Keegan, Steven M Horwitz

Faculty, Staff and Student Publications

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative …

Acute Myeloid Leukemia Management And Research In 2025, Hagop M Kantarjian, Courtney D Dinardo, Tapan M Kadia, Naval G Daver, Jessica K Altman, Eytan M Stein, Elias Jabbour, Charles A Schiffer, Amy Lang, Farhad Ravandi

Faculty, Staff and Student Publications

The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 …

Exercise And Nutrition To Improve Cancer Treatment-Related Outcomes (Enicto), Kathryn H Schmitz, Justin C Brown, Melinda L Irwin, Kim Robien, Jessica M Scott, Nathan A Berger, Bette Caan, Andrea Cercek, Tracy E Crane, Scott R Evans, Jennifer A Ligibel, Jeffrey A Meyerhardt, Tanya Agurs-Collins, Karen Basen-Engquist, Jennifer W Bea, Sheng F Cai, Brenda Cartmel, Vernon M Chinchilli, Wendy Demark-Wahnefried, Christina M Dieli-Conwright, Loretta Dipietro, Shawna E Doerksen, Sharon L Edelstein, Joanne Elena, William Evans, Leah M Ferrucci, Julia Foldi, Sarah Freylersythe, Helena Furberg, Lee W Jones, Ross Levine, Chaya S Moskowitz, Cynthia Owusu, Frank Penedo, Borsika A Rabin, Elena Ratner, Margaret Rosenzweig, Talya Salz, Tara Sanft, Matthew Schlumbrecht, Guillaume Spielmann, Cynthia A Thomson, Ashley H Tjaden, Martin R Weiser, Shengping Yang, Anthony F Yu, Frank M Perna, Enicto Consortium

Faculty, Staff and Student Publications

Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the …

Efficacy Of A Smartphone Application Assisting Home-Based Rehabilitation And Symptom Management For Patients With Lung Cancer Undergoing Video-Assisted Thoracoscopic Lobectomy: A Prospective, Single-Blinded, Randomised Control Trial (Popper Study, Chao Lv, Fangliang Lu, Xiugeng Zhou, Xiang Li, Wenhua Yu, Chune Zhang, Kaishen Chen, Songtao Du, Chao Han, Jia Wang, Yuzhao Wang, Shaolei Li, Liang Wang, Yinan Liu, Shanyuan Zhang, Miao Huang, Dongdong Song, Dachuan Zhao, Bing Liu, Yaqi Wang, Xinrun Cui, Zhiwei Zhou, Shi Yan, Nan Wu

Faculty, Staff and Student Publications

Background: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and postdischarge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation.

Methods: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. The authors screened 265 patients …

The Impact Of A Small-Group Mammography Video Discussion On Promoting Screening Uptake Among Nonadherent Chinese American Immigrant Women: A Randomized Controlled Trial, Naomi Q P Tan, Grace X Ma, Annette E Maxwell, Roger L Brown, Kathy Zhou, Alice Loh, Lucy Young, Robert J Volk, Qian Lu, Judy Huei-Yu Wang

Faculty, Staff and Student Publications

Background: The objective of this study was to evaluate the efficacy of an in-person, small-group mammography video discussion (SMVD) intervention on mammography uptake among nonadherent Chinese American immigrant women.

Methods: Women (N = 956) were randomized into either an SMVD group, where Chinese-speaking community health workers (CHWs) used an effective, culturally appropriate video to discuss mammography, or a video-only group, which viewed the cultural video sent by mail. Outcomes were mammography uptake at 6 months and 21 months postintervention.

Results: Women in both groups increased mammography uptake, and an outcome analysis revealed no group differences (adjusted odds ratio [AOR], 1.18; …

Predicting Sinonasal Inverted Papilloma Attachment Using Machine Learning: Current Lessons And Future Directions, Sean P Mckee, Xiaomin Liang, William C Yao, Brady Anderson, Jumah G Ahmad, David Z Allen, Salman Hasan, Andy J Chua, Chinmay Mokashi, Samia Islam, Amber U Luong, Martin J Citardi, Luca Giancardo

Faculty, Staff and Student Publications

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed. The tumor attachment site was manually segmented on CT scans by the operating surgeon. We used a nnU-Net model, a state-of-the-art deep learning-based segmentation algorithm that automatically configures image preprocessing, network architecture, training, and post-processing to identify the IP attachment site. The model was trained and evaluated using a 5-fold cross …

Empathy Unmasked: Patient Perception Of Physician Empathy In An Oncologic Emergency Setting A Randomized Controlled Trial Comparing Personal Protective Equipment Wear Versus Unmasked Video Communication, Kathryn J Burk, John J Stroh, Kelly Larkin, Patrick Chaftari, Denise M Langabeer, Jazmin R Menendez, Jeanie F Woodruff, Jan Hargrave, Hongxu Zhu, James P Long, Sai-Ching J Yeung, Kumar Alagappan, Aiham Qdaisat

Faculty, Staff and Student Publications

Background: Amidst the COVID-19 pandemic, telemedicine emerged as an important option that supports and facilitates clinical practice, however, its usefulness in emergency settings that treat patients with cancer is unclear.

Objective: To evaluate patient perception of physician empathy in an emergency oncology setting, comparing video interaction to an in-person with personal protective equipment (PPE) approach.

Methods: In this single-center, prospective, cross-sectional, survey-based randomized controlled trial, patients were randomized 1:1 for the concluding conversation done in-person which included either interacting with physicians wearing PPE or video interaction with physicians without PPE (virtual). Patients' perceptions of the physicians' relational empathy were assessed …

Weighted Hypoxemia Index: An Adaptable Method For Quantifying Hypoxemia Severity, Diane C Lim, Cheng-Bang Chen, Ankita Paul, Yujie Wang, Jinyoung Kim, Soonhyun Yook, Emily Y Kim, Edison Q Kim, Anup Das, Medhi Wangpaichitr, Virend K Somers, Chi Hang Lee, Phyllis C Zee, Toshihiro Imamura, Hosung Kim

Faculty, Staff and Student Publications

Objective: To quantitate hypoxemia severity.

Methods: We developed the Weighted Hypoxemia Index to be adapted to different clinical settings by applying 5 steps to the oxygen saturation curve: (1) Identify desaturation/resaturation event [Formula: see text] by setting the upper threshold; (2) Exclude events as artifact by setting a lower threshold; (3) Calculate weighted area for each [Formula: see text] as [Formula: see text]; (4) Calculate a normalization factor [Formula: see text] for each subject; (5) Calculate the Weighted Hypoxemia Index as the summation of all weighted areas multiplied by [Formula: see text]. We assessed the Weighted Hypoxemia Index predictive value …

Enl Mutation And Aml: A New Model That Reveals Oncogenic Condensate’S Function In Leukemogenesis, Zhong Fan, Yanan Jiang, Xiaotian Zhang

Faculty, Staff and Student Publications

Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y et al. (2023) Nat Chem Biol 19, 1223-1234; Chandra B et al. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations …

Stat3 Inhibition In Combination With Cd47 Blockade Inhibits Osteosarcoma Lung Metastasis, Pradeep Shrestha, Rejeena Shrestha, You Zhou, Rafal Zielinski, Waldemar Priebe, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: New therapies are urgently needed for patients with osteosarcoma (OS). STAT3 and CD47 are potential therapeutic target in OS. Here we investigated the therapeutic activity of the orally bioavailable STAT3 inhibitor, WP1066, and anti-CD47 antibody using OS mouse models.

Methods: Cytotoxic effect of WP1066 against OS cell lines and its immunomodulatory effects were evaluated in vitro. Experimental metastasis and orthotopic syngeneic mouse models were used to investigate the therapeutic efficacy of WP1066 and anti-CD47 antibody. Further flow cytometric analysis was performed.

Results: STAT3 was constitutively activated in multiple human and mouse OS cell lines. WP1066 suppressed STAT3 activation …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Ganglioside Gd2 Contributes To A Stem-Like Phenotype In Intrahepatic Cholangiocarcinoma, Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Tiziano Lottini, Benedetta Piombanti, Ignazia Tusa, Elisabetta Rovida, Cédric Coulouarn, Jesper B Andersen, Monika Lewinska, Claudia Campani, V Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Faculty, Staff and Student Publications

BACKGROUND & AIMS: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

METHODS: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The …

Ft538, Ipsc-Derived Nk Cells, Enhance Aml Cell Killing When Combined With Chemotherapy, Amanda Eckstrom, Anudishi Tyagi, Sajid Mahmood, Lilly Wong, Bahram Valamehr, Adishwar Rao, Akriti Agrawal, Maryam Siddiqui, V Lokesh Battula

Faculty, Staff and Student Publications

Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines …

Epidemiology Of Patient Record Duplication, Onur Sahin, Audrey Zhao, Reuben Joseph Applegate, Todd R Johnson, Elmer V Bernstam

Faculty, Staff and Student Publications

Objectives: Duplicate patient records can increase costs and medical errors. We assessed the association between demographic factors, comorbidities, health care usage, and duplicate electronic health records.

Methods: We analyzed the association between duplicate patient records and multiple demographic variables (race, Hispanic ethnicity, sex, and age) as well as the Charlson Comorbidity Index (CCI), number of diagnoses, and number of health care encounters. The study population included 3,018,413 patients seen at a large urban academic medical center with at least one recorded diagnosis. Duplication of patient medical records was determined by using a previously validated enterprise Master Person Index.

Results: Unknown …

Quantitatively Assessing The Impact Of The Quality Of Snomed Ct Subtype Hierarchy On Cohort Queries, Xubing Hao, Xiaojin Li, Yan Huang, Jay Shi, Rashmie Abeysinghe, Cui Tao, Kirk Roberts, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Objective: SNOMED CT provides a standardized terminology for clinical concepts, allowing cohort queries over heterogeneous clinical data including Electronic Health Records (EHRs). While it is intuitive that missing and inaccurate subtype (or is-a) relations in SNOMED CT reduce the recall and precision of cohort queries, the extent of these impacts has not been formally assessed. This study fills this gap by developing quantitative metrics to measure these impacts and performing statistical analysis on their significance.

Material and methods: We used the Optum de-identified COVID-19 Electronic Health Record dataset. We defined micro-averaged and macro-averaged recall and precision metrics to assess the …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Zika Virus Modulates Arthropod Histone Methylation For Its Survival In Mosquito Cells, Telvin Harrell

Biological Sciences Faculty Publications

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with …

Switching To Tumescent Dissection In Mastectomy, Emna Bakillah, Ari Brooks, Seye Adekeye

Department of Surgery Faculty Papers

Introduction: Tumescent dissection (TUM) combines the use of crystalloid, local anesthetic, and epinephrine to create a bloodless plane to raise skin flaps. We aim to compare outcomes of TUM versus standard electrocautery dissection in mastectomies with and without reconstruction. Methods: We conducted a retrospective cohort study of patients who underwent mastectomy by a single surgeon between January 2016 and October 2020 utilizing the electronic medical record. The primary outcome was complication rate, and the secondary outcome was operative time. Chi-squared analysis and two-sample t-tests were used to examine outcomes. Results: Among 242 patients, 141 patients underwent TUM and 101 …