Medical Specialties Commons^™

Integrated Molecular And Multiparametric Mri Mapping Of High-Grade Glioma Identifies Regional Biologic Signatures, Leland S Hu, Fulvio D'Angelo, Taylor M Weiskittel, Francesca P Caruso, Shannon P Fortin Ensign, Mylan R Blomquist, Matthew J Flick, Lujia Wang, Christopher P Sereduk, Kevin Meng-Lin, Gustavo De Leon, Ashley Nespodzany, Javier C Urcuyo, Ashlyn C Gonzales, Lee Curtin, Erika M Lewis, Kyle W Singleton, Timothy Dondlinger, Aliya Anil, Natenael B Semmineh, Teresa Noviello, Reyna A Patel, Panwen Wang, Junwen Wang, Jennifer M Eschbacher, Andrea Hawkins-Daarud, Pamela R Jackson, Itamar S Grunfeld, Christian Elrod, Gina L Mazza, Sam C Mcgee, Lisa Paulson, Kamala Clark-Swanson, Yvette Lassiter-Morris, Kris A Smith, Peter Nakaji, Bernard R Bendok, Richard S Zimmerman, Chandan Krishna, Devi P Patra, Naresh P Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej M Mrugala, Alyx B Porter, Scott C Beeman, Todd R Jensen, Kathleen M Schmainda, Yuxiang Zhou, Leslie C Baxter, Christopher L Plaisier, Jing Li, Hu Li, Anna Lasorella, C Chad Quarles, Kristin R Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L Tran

Faculty, Staff and Student Publications

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate …

National Survey On The Availability Of Oncology Palliative Care Services At Tertiary General And Cancer Hospitals In China, Xiaomei Li, Xin Shelley Wang, Haili Huang, Miao Liu, Yinan Wu, Jiaojiao Qiu, Boran Zhang, Linhong Cui, David Hui

Faculty, Staff and Student Publications

Background: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China.

Methods: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service.

Results: Most responders …

Antibodies To Coagulase Of Staphylococcus Aureus Crossreact To Efb And Reveal Different Binding Of Shared Fibrinogen Binding Repeats, Federico Bertoglio, Ya-Ping Ko, Sheila Thomas, Liliana Giordano, Francesca Romana Scommegna, Doris Meier, Saskia Polten, Marlies Becker, Srishtee Arora, Michael Hust, Magnus Höök, Livia Visai

Faculty, Staff and Student Publications

Staphylococcus aureus pathology is caused by a plethora of virulence factors able to combat multiple host defence mechanisms. Fibrinogen (Fg), a critical component in the host coagulation cascade, plays an important role in the pathogenesis of this bacterium, as it is the target of numerous staphylococcal virulence proteins. Amongst its secreted virulence factors, coagulase (Coa) and Extracellular fibrinogen-binding protein (Efb) share common Fg binding motives and have been described to form a Fg shield around staphylococcal cells, thereby allowing efficient bacterial spreading, phagocytosis escape and evasion of host immune system responses. Targeting these proteins with monoclonal antibodies thus represents a …

Author Correction: Synthetic Oct-A Blood Vessel Maps Using Fundus Images And Generative Adversarial Networks, Ivan Coronado, Samiksha Pachade, Emanuele Trucco, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino-Cole, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

No abstract provided.

Differential Effects Of Pancreatic Cancer-Derived Extracellular Vesicles Driving A Suppressive Environment, Anurag Purushothaman, Jacqueline Oliva-Ramírez, Warapen Treekitkarnmongkol, Deivendran Sankaran, Mark W Hurd, Nagireddy Putluri, Anirban Maitra, Cara Haymaker, Subrata Sen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) cells display extensive crosstalk with their surrounding environment to regulate tumor growth, immune evasion, and metastasis. Recent advances have attributed many of these interactions to intercellular communication mediated by small extracellular vesicles (sEVs), involving cancer-associated fibroblasts (CAF). To explore the impact of sEVs on monocyte lineage transition as well as the expression of checkpoint receptors and activation markers, peripheral blood monocytes from healthy subjects were exposed to PDAC-derived sEVs. Additionally, to analyze the role of sEV-associated HA in immune regulation and tissue-resident fibroblasts, monocytes and pancreatic stellate cells were cultured in the presence of PDAC sEVs …

Axl-Initiated Paracrine Activation Of Pstat3 Enhances Mesenchymal And Vasculogenic Supportive Features Of Tumor-Associated Macrophages, Chia-Nung Hung, Meizhen Chen, Daniel T Dearmond, Cheryl H-L Chiu, Catherine A Limboy, Xi Tan, Meena Kusi, Chih-Wei Chou, Li-Ling Lin, Zhao Zhang, Chiou-Miin Wang, Chun-Liang Chen, Kohzoh Mitsuya, Pawel A Osmulski, Maria E Gaczynska, Nameer B Kirma, Ratna K Vadlamudi, Don L Gibbons, Steve Warner, Andrew J Brenner, Daruka Mahadevan, Joel E Michalek, Tim H-M Huang, Josephine A Taverna

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to …

A Peptide-Binding Domain Shared With An Antarctic Bacterium Facilitates, Cameron J Lloyd, Shuaiqi Guo, Brett Kinrade, Hossein Zahiri, Robert Eves, Syed Khalid Ali, Fitnat Yildiz, Ilja K Voets, Peter L Davies, Karl E Klose

Faculty, Staff and Student Publications

No abstract provided.

Interpreting Randomized Controlled Trials, Pavlos Msaouel, Juhee Lee, Peter F Thall

Faculty, Staff and Student Publications

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial's sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as executed in surveys. We argue that group-specific statistics, …

Social Vulnerability Of The People Exposed To Wildfires In Us West Coast States, Arash Modaresi Rad, John T Abatzoglou, Erica Fleishman, Miranda H Mockrin, Volker C Radeloff, Yavar Pourmohamad, Megan Cattau, J Michael Johnson, Philip Higuera, Nicholas J Nauslar, Mojtaba Sadegh

Faculty, Staff and Student Publications

Understanding of the vulnerability of populations exposed to wildfires is limited. We used an index from the U.S. Centers for Disease Control and Prevention to assess the social vulnerability of populations exposed to wildfire from 2000-2021 in California, Oregon, and Washington, which accounted for 90% of exposures in the western United States. The number of people exposed to fire from 2000-2010 to 2011-2021 increased substantially, with the largest increase, nearly 250%, for people with high social vulnerability. In Oregon and Washington, a higher percentage of exposed people were highly vulnerable (>40%) than in California (~8%). Increased social vulnerability of …

Response Patterns And Impact Of Mrd In Patients With Idh1/2-Mutated Aml Treated With Venetoclax And Hypomethylating Agents, Danielle Hammond, Sanam Loghavi, Sa A Wang, Marina Y Konopleva, Tapan M Kadia, Naval G Daver, Maro Ohanian, Ghayas C Issa, Yesid Alvarado, Nicholas J Short, Koji Sasaki, Naveen Pemmaraju, Guillermo Montalban-Bravo, Curtis A Lachowiez, Abhishek Maiti, Guillermo Garcia-Manero, Elias J Jabbour, Gautam Borthakur, Farhad Ravandi, Koichi Takahashi, Sherry R Pierce, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

No abstract provided.

Epichaperome Inhibition Targets Tp53-Mutant Aml And Aml Stem/Progenitor Cells, Bing Z Carter, Po Yee Mak, Muharrem Muftuoglu, Wenjing Tao, Baozhen Ke, Jingqi Pei, Andrea D Bedoy, Lauren B Ostermann, Yuki Nishida, Sevinj Isgandarova, Mary Sobieski, Nghi Nguyen, Reid T Powell, Margarita Martinez-Moczygemba, Clifford Stephan, Mahesh Basyal, Naveen Pemmaraju, Steffen Boettcher, Benjamin L Ebert, Elizabeth J Shpall, Barbara Wallner, Robert A Morgan, Georgios I Karras, Ute M Moll, Michael Andreeff

Faculty, Staff and Student Publications

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to …

Critical Functions Of Extracellular Matrix In Brain Metastasis Seeding, Arseniy E Yuzhalin, Dihua Yu

Faculty, Staff and Student Publications

Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not be underestimated. Brain metastasis is a serious complication of cancer, and recent findings highlighted the contribution of ECM in brain metastasis development. In this review, we provide a comprehensive outlook on how ECM proteins promote brain metastasis seeding. In particular, we discuss (1) disruption of the blood-brain barrier in brain metastasis; (2) role of ECM in modulating brain metastasis dormancy; (3) regulation of brain metastasis seeding by ECM-activated integrin signaling; (4) functions of …

Mortality Benefit Of A Blood-Based Biomarker Panel For Lung Cancer On The Basis Of The Prostate, Lung, Colorectal, And Ovarian Cohort, Ehsan Irajizad, Johannes F Fahrmann, Tracey Marsh, Jody Vykoukal, Jennifer B Dennison, James P Long, Kim-Anh Do, Ziding Feng, Samir Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Purpose: To investigate the utility of integrating a panel of circulating protein biomarkers in combination with a risk model on the basis of subject characteristics to identify individuals at high risk of harboring a lethal lung cancer.

Methods: Data from an established logistic regression model that combines four-marker protein panel (4MP) together with the Prostate, Lung, Colorectal, and Ovarian (PLCO) risk model (PLCOm2012) assayed in prediagnostic sera from 552 lung cancer cases and 2,193 noncases from the PLCO cohort were used in this study. Of the 552 lung cancer cases, 387 (70%) died of lung cancer. Cumulative incidence of lung …

Polygenic Risk And Chemotherapy-Related Subsequent Malignancies In Childhood Cancer Survivors: A Childhood Cancer Survivor Study And St Jude Lifetime Cohort Study Report, Cindy Im, Noha Sharafeldin, Yan Yuan, Zhaoming Wang, Yadav Sapkota, Zhanni Lu, Logan G Spector, Rebecca M Howell, Michael A Arnold, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Smita Bhatia, Gregory T Armstrong, Joseph P Neglia, Yutaka Yasui, Lucie M Turcotte

Faculty, Staff and Student Publications

Purpose: Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases.

Patients and methods: SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS …

Standardized Definitions For Efficacy End Points In Neoadjuvant Breast Cancer Clinical Trials: Neosteep, Jennifer K Litton, Meredith M Regan, Lajos Pusztai, Hope S Rugo, Sara M Tolaney, Elizabeth Garrett-Mayer, Laleh Amiri-Kordestani, Reva K Basho, Ana F Best, Jean-Francois Boileau, Carsten Denkert, Jared C Foster, Nadia Harbeck, Heather A Jacene, Tari A King, Ginny Mason, Ciara C O'Sullivan, Tatiana M Prowell, Andrea L Richardson, Karla A Sepulveda, Mary Lou Smith, Judy A Tjoe, Gulisa Turashvili, Wendy A Woodward, Lynn Pearson Butler, Elena I Schwartz, Larissa A Korde

Faculty, Staff and Student Publications

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points.

METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at …

Abcc1 And Glutathione Metabolism Limit The Efficacy Of Bcl-2 Inhibitors In Acute Myeloid Leukemia, Jessica Ebner, Johannes Schmoellerl, Martin Piontek, Gabriele Manhart, Selina Troester, Bing Z Carter, Heidi Neubauer, Richard Moriggl, Gergely Szakács, Johannes Zuber, Thomas Köcher, Michael Andreeff, Wolfgang R Sperr, Peter Valent, Florian Grebien

Faculty, Staff and Student Publications

The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels …

Mir-146a Inhibits Ovarian Tumor Growth In Vivo Via Targeting Immunosuppressive Neutrophils And Enhancing Cd8+ T Cell Infiltration, Rui Chen, Elaina Coleborn, Chintan Bhavsar, Yue Wang, Louisa Alim, Andrew N Wilkinson, Michelle A Tran, Gowri Irgam, Sharat Atluri, Kiefer Wong, Jae-Jun Shim, Siddharth Adityan, Ju-Seog Lee, Willem W Overwijk, Raymond Steptoe, Da Yang, Sherry Y Wu

Faculty, Staff and Student Publications

Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53−/− and IG10 murine HGSC models. Increasing miR-146a expression …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

Deep Learning Integrates Histopathology And Proteogenomics At A Pan-Cancer Level, Joshua M Wang, Runyu Hong, Elizabeth G Demicco, Jimin Tan, Rossana Lazcano, Andre L Moreira, Yize Li, Anna Calinawan, Narges Razavian, Tobias Schraink, Michael A Gillette, Gilbert S Omenn, Eunkyung An, Henry Rodriguez, Aristotelis Tsirigos, Kelly V Ruggles, Li Ding, Ana I Robles, D R Mani, Karin D Rodland, Alexander J Lazar, Wenke Liu, David Fenyö, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) and tissue-of-origin (AUROC = 0.979). We further investigate predictive power on tasks not normally performed from H&E alone, including TP53 prediction and pathologic stage. Importantly, we describe predictive morphologies not previously utilized in a clinical setting. The incorporation of transcriptomics and proteomics identifies pathway-level …

Targeted Single-Cell Proteomic Analysis Identifies New Liquid Biopsy Biomarkers Associated With Multiple Myeloma, Sonia M Setayesh, Libere J Ndacayisaba, Kate E Rappard, Valerie Hennes, Luz Yurany Moreno Rueda, Guilin Tang, Pei Lin, Robert Z Orlowski, David E Symer, Elisabet E Manasanch, Stephanie N Shishido, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) is accompanied by alterations to the normal plasma cell (PC) proteome, leading to changes to the tumor microenvironment and disease progression. There is a great need for understanding the consequences that lead to MM progression and for the discovery of new biomarkers that can aid clinical diagnostics and serve as targets for therapeutics. This study demonstrates the applicability of utilizing the single-cell high-definition liquid biopsy assay (HDSCA) and imaging mass cytometry to characterize the proteomic profile of myeloma. In our study, we analyzed ~87,000 cells from seven patient samples (bone marrow and peripheral blood) across the myeloma …

Aspergillus Flavus And Fusarium Verticillioides And Their Main Mycotoxins: Global Distribution And Scenarios Of Interactions In Maize, Xiangrong Chen, Mohamed F Abdallah, Sofie Landschoot, Kris Audenaert, Sarah De Saeger, Xiangfeng Chen, Andreja Rajkovic

Faculty, Staff and Student Publications

Maize is frequently contaminated with multiple mycotoxins, especially those produced by Aspergillus flavus and Fusarium verticillioides. As mycotoxin contamination is a critical factor that destabilizes global food safety, the current review provides an updated overview of the (co-)occurrence of A. flavus and F. verticillioides and (co-)contamination of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in maize. Furthermore, it summarizes their interactions in maize. The gathered data predict the (co-)occurrence and virulence of A. flavus and F. verticillioides would increase worldwide, especially in European cold climate countries. Studies on the interaction of both fungi regarding their growth mainly showed antagonistic …

Retraction Note: Mir20a/106a-Wtx Axis Regulates Rhogdia/Cdc42 Signaling And Colon Cancer Progression, Gui-Fang Zhu, Yang-Wei Xu, Jian Li, Hui-Lin Niu, Wen-Xia Ma, Jia Xu, Pei-Rong Zhou, Xia Liu, Dan-Li Ye, Xiao-Rong Liu, Tao Yan, Wei-Ke Zhai, Zhi-Jun Xu, Chun Liu, Lei Wang, Hao Wang, Jia-Mao Luo, Li Liu, Xuan-Qi Li, Suiqun Guo, Hui-Ping Jiang, Peng Shen, Hui-Kuan Lin, Di-Hua Yu, Yan-Qing Ding, Qing-Ling Zhang

Faculty, Staff and Student Publications

No abstract provided.

Neuroimmune Support Of Neuronal Regeneration And Neuroplasticity Following Cerebral Ischemia In Juvenile Mice, Ricaurte A Marquez-Ortiz, Vesna Tesic, Daniel R Hernandez, Bilkis Akhter, Nibedita Aich, Porter M Boudreaux, Garrett A Clemons, Celeste Yin-Chieh Wu, Hung Wen Lin, Krista M Rodgers

Faculty, Staff and Student Publications

Ischemic damage to the brain and loss of neurons contribute to functional disabilities in many stroke survivors. Recovery of neuroplasticity is critical to restoration of function and improved quality of life. Stroke and neurological deficits occur in both adults and children, and yet it is well documented that the developing brain has remarkable plasticity which promotes increased post-ischemic functional recovery compared with adults. However, the mechanisms underlying post-stroke recovery in the young brain have not been fully explored. We observed opposing responses to experimental cerebral ischemia in juvenile and adult mice, with substantial neural regeneration and enhanced neuroplasticity detected in …

A Review Of The Role Of Tendon Stem Cells In Tendon-Bone Regeneration, Junjie Chen, Chuanfeng Jiang, Lu Yin, Yingqi Liu, Yue He, Sen Li, Huarui Shen

Faculty, Staff and Student Publications

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has …

Immune-Active Tumor-Adjacent Tissues Are Associated With Favorable Prognosis In Stage I Lung Squamous Cell Carcinoma, Lisha Ying, Chunliu Zhang, Alexandre Reuben, Yiping Tian, Jiaoyue Jin, Canming Wang, Jing Bai, Xinyuan Liu, Jianfei Fang, Tingting Feng, Chenyang Xu, Rui Zhu, Minran Huang, Yingqi Lyu, Tingting Lu, Xiaodan Pan, Jianjun Zhang, Dan Su

Faculty, Staff and Student Publications

The immunogenomic features of tumor-adjacent lungs (TALs) in stage I lung squamous cell carcinoma (LUSC) are not clear. Multiomics analyses of tumor tissues and paired TALs from 59 stage I LUSC patients were performed. Compared to tumors, TALs exhibited a better-preserved immune contexture indicated by upregulation of immune pathways, increased immune infiltration, and higher expression of immune effector molecules. Notably, TALs had no mutations in PTEN and KEAP1, a lower incidence of human leukocyte antigen (HLA) loss and higher expression of HLA class I genes, major histocompatibility complex (MHC) I chaperones, and interferon (IFN)-γ-associated genes. Digital spatial profiling validated the …

Advance Directives For Patients With Breast Cancer: Applying The Right Info/Right Care/Right Patient/Right Time Oncology Model, Stephanie Ossowski, Liisa Lyon, Elizabeth Linehan, Nancy P Gordon, Olga Egorova, Becky Mark, Kimberly Beringer, Thea Abbe, Aida Shirazi, Christine Weldon, Julia Trosman, Arliene Ravelo, Raymond Liu

Faculty, Staff and Student Publications

Background Advance directives (AD) are an important component of life care planning for patients undergoing treatment for cancer; however, there are few effective interventions to increase AD rates. In this quality improvement project, the authors integrated AD counseling into a novel right info/right care/right patient/right time (4R) sequence of care oncology delivery intervention for breast cancer patients in an integrated health care delivery system. Methods The authors studied two groups of patients with newly diagnosed breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at a single facility. The usual care (UC) cohort (N = 139) received care …

Neurocognitive Outcomes In Adult Survivors Of Neuroblastoma: A Report From The Childhood Cancer Survivor Study, Caroline Hesko, Wei Liu, Deo K Srivastava, Tara M Brinkman, Lisa Diller, Todd M Gibson, Kevin C Oeffinger, Wendy M Leisenring, Rebecca Howell, Gregory T Armstrong, Kevin R Krull, Tara O Henderson

Faculty, Staff and Student Publications

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease.

Results: Survivors (N = 837; median …

Precision Modulation Of Dysbiotic Adult Microbiomes With A Human-Milk-Derived Synbiotic Reshapes Gut Microbial Composition And Metabolites, Julie E Button, Casey M Cosetta, Abigail L Reens, Sarah L Brooker, Aislinn D Rowan-Nash, Richard C Lavin, Russell Saur, Shuning Zheng, Chloe A Autran, Martin L Lee, Adam K Sun, Amin M Alousi, Christine B Peterson, Andrew Y Koh, David J Rechtman, Robert R Jenq, Gregory J Mckenzie

Faculty, Staff and Student Publications

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol …

Dosimetry Of A Novel 111indium-Labeled Anti-P-Cadherin Monoclonal Antibody (Ff-21101) In Non-Human Primates, Gregory Ravizzini, William Erwin, Louis De Palatis, Lucia Martiniova, Vivek Subbiah, Vincenzo Paolillo, Jennifer Mitchell, Asa P Mccoy, Jose Gonzalez, Osama Mawlawi

Faculty, Staff and Student Publications

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …