Digital Commons Network^™

Rad51 Foci As A Biomarker Predictive Of Platinum Chemotherapy Response In Ovarian Cancer, Amanda J Compadre, Lillian N Van Biljon, Mark C Valentine, Emily Graham, Bisiayo Fashemi, Emilee N Kotnik, Isaac Cooper, Lindsay M Kuroki, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, David G Mutch, Matthew A Powell, Lulu Sun, Nima Mosammaparast, Peinan Zhao, Elena Lomonosova, Dineo Khabele, Mary M Mullen, Et Al.

2020-Current year OA Pubs

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell …

A Phase Ib/Ii Study Of Ivosidenib With Venetoclax ± Azacitidine In Idh1-Mutated Myeloid Malignancies, Curtis A Lachowiez, Sanam Loghavi, Zhihong Zeng, Tomoyuki Tanaka, Yi June Kim, Hidetaka Uryu, Sven Turkalj, Niels Asger Jakobsen, Marlise R Luskin, Dzifa Y Duose, Rebecca S S Tidwell, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Lucia Masarova, George D Tippett, Prithviraj Bose, Elias J Jabbour, Farhad Ravandi, Naval G Daver, Guillermo Garcia-Manero, Hagop Kantarjian, Jacqueline S Garcia, Paresh Vyas, Koichi Takahashi, Marina Konopleva, Courtney D Dinardo

Faculty, Staff and Student Publications

UNLABELLED: The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD--negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving …

Human Gut Bacteria Tailor Extracellular Vesicle Cargo For The Breakdown Of Diet- And Host-Derived Glycans, Mariana G Sartorio, Evan J Pardue, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Extracellular vesicles are produced in all three domains of life, and their biogenesis has common ancient origins in eukaryotes and archaea. Although bacterial vesicles were discovered several decades ago and multiple roles have been attributed to them, no mechanism has been established for vesicles biogenesis in bacteria. For this reason, there is a significant level of skepticism about the biological relevance of bacterial vesicles.

Loss Of The Batten Disease Protein Cln3 Leads To Mis-Trafficking Of M6pr And Defective Autophagic-Lysosomal Reformation, Alessia Calcagni', Leopoldo Staiano, Nicolina Zampelli, Nadia Minopoli, Niculin J Herz, Giuseppe Di Tullio, Tuong Huynh, Jlenia Monfregola, Alessandra Esposito, Carmine Cirillo, Aleksandar Bajic, Mahla Zahabiyon, Rachel Curnock, Elena Polishchuk, Luke Parkitny, Diego Luis Medina, Nunzia Pastore, Peter J Cullen, Giancarlo Parenti, Maria Antonietta De Matteis, Paolo Grumati, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our …

A Rapid Cell-Free Expression And Screening Platform For Antibody Discovery, Andrew C Hunt, Bastian Vögeli, Ahmed O Hassan, Laura Guerrero, Weston Kightlinger, Danielle J Yoesep, Antje Krüger, Madison Dewinter, Michael S Diamond, Ashty S Karim, Michael C Jewett

2020-Current year OA Pubs

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike …

Radiomics Characterization Of Tissues In An Animal Brain Tumor Model Imaged Using Dynamic Contrast Enhanced (Dce) Mri, Hassan Bagher-Ebadian, Stephen L. Brown, Mohammad M. Ghassemi, Tavarekere N. Nagaraja, Benjamin Movsas, James R. Ewing, Indrin J. Chetty

Radiation Oncology Articles

Here, we investigate radiomics-based characterization of tumor vascular and microenvironmental properties in an orthotopic rat brain tumor model measured using dynamic-contrast-enhanced (DCE) MRI. Thirty-two immune compromised-RNU rats implanted with human U-251N cancer cells were imaged using DCE-MRI (7Tesla, Dual-Gradient-Echo). The aim was to perform pharmacokinetic analysis using a nested model (NM) selection technique to classify brain regions according to vasculature properties considered as the source of truth. A two-dimensional convolutional-based radiomics analysis was performed on the raw-DCE-MRI of the rat brains to generate dynamic radiomics maps. The raw-DCE-MRI and respective radiomics maps were used to build 28 unsupervised Kohonen self-organizing-maps …

Autologous Humanized Pdx Modeling For Immuno-Oncology Recapitulates Features Of The Human Tumor Microenvironment., Michael Chiorazzi, Jan Martinek, Bradley Krasnick, Yunjiang Zheng, Keenan J Robbins, Rihao Qu, Gabriel Kaufmann, Zachary Skidmore, Melani Juric, Laura A Henze, Frederic Brösecke, Adam Adonyi, Jun Zhao, Liang Shan, Esen Sefik, Jacqueline Mudd, Ye Bi, S Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Sofia Fertuzinhos, Rolando Garcia-Milian, Daniel Boffa, Frank Detterbeck, Andrew Dhanasopon, Justin Blasberg, Benjamin Judson, Scott Gettinger, Katerina Politi, Yuval Kluger, Karolina Palucka, Ryan C Fields, Richard A Flavell

Faculty Research 2023

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. …

The Effects Of Natural Epigenetic Therapies In 3d Ovarian Cancer And Patient-Derived Tumor Explants: New Avenues In Regulating The Cancer Secretome., Rebeca Kelly, Diego Aviles, Catriona Krisulevicz, Krystal Hunter, Lauren Krill, David Warshal, Olga Ostrovsky

Cooper Medical School of Rowan University Departmental Research

High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in …

An Rrna Fragment In Extracellular Vesicles Secreted By Human Airway Epithelial Cells Increases The Fluoroquinolone Sensitivity Of P. Aeruginosa, Katja Koeppen, Thomas H Hampton, Roxanna Barnaby, Carolyn Roche, Scott A Gerber, Young Ah Goo, Byoung-Kyu Cho, Danielle M Vermilyea, Deborah A Hogan, Bruce A Stanton

2020-Current year OA Pubs

Lung infections caused by antibiotic-resistant strains of

Artist's Statement: Foreground/Background, Tahira Scholle

Faculty, Staff and Students Publications

No abstract provided.

Multiple Sterile Withdrawals From Iohexol Bottles Does Not Increase Contamination Risk, Caroline Purtill, Manraj Dhesi, Daniel Haber, Nicholas D'Antonio, Noreen J. Hickok, Jeremy I. Simon

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is a global shortage of iohexol contrast media, commonly used in epidural injections, as a result of lockdown and decreased production due to COVID-19. Iohexol bottles are designated for single use, which, depending on the vials available, often leads to wasting up to 95% of this limited resource. However, avoiding multiple withdrawals may be unnecessary if withdrawing multiple times using sterile technique does not increase the risk for contamination.

OBJECTIVES: The purpose of our study is to determine whether multiple withdrawals from iohexol injection bottles using a sterile technique poses a greater risk of introducing contaminants than a …

Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …

Outersphere Approach To Increasing The Persistance Of Oxygen-Sensitive Europium(Ii)-Containing Contrast Agents For Magnetic Resonance Imaging With Perfluorocarbon Nanoemulsions Toward Imaging Of Hypoxia, Jacob C Lutter, Andrea L Batchev, Caitlyn J Ortiz, Alexander G Sertage, Jonathan Romero, S A Amali S Subasinghe, Steen E Pedersen, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of EuII are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon-nanoemulsion perfused with N2, forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon-soluble complex of EuII. Conversion of the perfluorocarbon solution of EuII into nanoemulsions results in observable differences between reduced and oxidized forms by MRI both in vitro and in vivo. Oxidation in vivo occurrs over a period of ~30 min compared to <5 min for a comparable EuII-containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of EuII-containing complexes in vivo for the study of hypoxia.

Ethical, Legal, And Social Implications Of Genomics Research: Implications For Building A More Racially Diverse Bioethics Workforce, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Effects Of Covid-19 On The Autonomic Cardiovascular System: Heart Rate Variability And Turbulence In Recovered Patients, Sedat Taş, Ümmü Taş

The Texas Heart Institute Journal

BACKGROUND: COVID-19 may be a risk factor for developing cardiovascular autonomic dysfunction. Data are limited, however, on the association between heart rate variability, heart rate turbulence, and COVID-19. The aims of this study were to evaluate the effect of COVID-19 on the cardiovascular autonomic system in patients with persistent symptoms after recovering from COVID-19 and to determine whether these patients showed changes in ambulatory electrocardiography monitoring.

METHODS: Fifty-one adults who had confirmed SARS-CoV-2 infection and presented with persistent symptoms to the cardiology outpatient clinic after clinical recovery between April and June 2021 were included. Patients were prospectively followed for 6 …

Identification Of Unique Α4 Chain Structure And Conserved Antiangiogenic Activity Of Α3nc1 Type Iv Collagen In Zebrafish, Valerie S Lebleu, Jianli Dai, Susan Tsutakawa, Brian A Macdonald, Joseph L Alge, Malin Sund, Liang Xie, Hikaru Sugimoto, John Tainer, Leonard I Zon, Raghu Kalluri

Faculty, Staff and Student Publications

BACKGROUND: Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1-α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.

RESULTS: We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in …

A Serological Assay To Detect And Differentiate Rodent Exposure To Soft Tick And Hard Tick Relapsing Fever Infections In The United States, Christina M Parise, Ying Bai, Kevin S Brandt, Shelby L Ford, Sarah Maes, Adam J Replogle, Alexander R Kneubehl, Job E Lopez, Rebecca J Eisen, Andrias Hojgaard

Faculty, Staff and Students Publications

Human cases of relapsing fever (RF) in North America are caused primarily by Borrelia hermsii and Borrelia turicatae, which are spread by argasid (soft) ticks, and by Borrelia miyamotoi, which is transmitted by ixodid (hard) ticks. In some regions of the United States, the ranges of the hard and soft tick RF species are known to overlap; in many areas, recorded ranges of RF spirochetes overlap with Lyme disease (LD) group Borrelia spirochetes. Identification of RF clusters or cases detected in unusual geographic localities might prompt public health agencies to investigate environmental exposures, enabling prevention of additional cases through locally …

Interactive Associations Of Eczema With Glutathione S-Transferase Genes In Relation To Autism Spectrum Disorder And Its Severity In Jamaican Children, Sepideh Saroukhani, Maureen Samms-Vaughan, Jan Bressler, Minjae Lee, Courtney Byrd-Williams, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Comorbidity of eczema with autism spectrum disorder (ASD) is increasing. We investigated the associations of eczema and its possible interaction with polymorphisms in glutathione S-transferase (GST) genes in relation to ASD and ASD severity.

METHOD: Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of eczema with GST genes in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domain-specific comparison scores (CSs) by fitting general linear …

Parametric Delineation Uncertainties Contouring (Pduc) Modeling On Ct Scans Of Prostate Cancer Patients, Vi Ly, Lizhong Liu, Carlos Cardenas, Sean Maroongroge, Brian De, Daniel El Basha, Laurence Court, Xi Luo

Faculty, Staff and Student Publications

PURPOSE: Variability in contouring contributes to large variations in radiation therapy planning and treatment outcomes. The development and testing of tools to automatically detect contouring errors require a source of contours that includes well-understood and realistic errors. The purpose of this work was to develop a simulation algorithm that intentionally injects errors of varying magnitudes into clinically accepted contours and produces realistic contours with different levels of variability.

METHODS: We used a dataset of CT scans from 14 prostate cancer patients with clinician-drawn contours of the regions of interest (ROI) of the prostate, bladder, and rectum. Using our newly developed …

Substrate Derived Sequences Act As Subsite-Blocking Motifs In Protease Inhibitory Antibodies, Hyunjun Choe, Tara Antee, Xin Ge

Faculty, Staff and Student Publications

Proteases are involved in many physiologic processes, and dysregulated proteolysis is basis of a variety of diseases. Specific inhibition of pathogenetic proteases via monoclonal antibodies therefore holds significant therapeutic promise. Inspired by the competitive mechanism utilized by many naturally occurring and man-made protease inhibitors, we hypothesized that substrate-like peptide sequences can act as protease subsite blocking motifs if they occupy only one side of the reaction center. To test this hypothesis, a degenerate codon library representing MMP-14 substrate profiles at P1-P5' positions was constructed in the context of an anti-MMP-14 Fab by replacing its inhibitory motif in CDR-H3 with MMP-14 …

Genome-Wide Association Study Of Thoracic Aortic Aneurysm And Dissection In The Million Veteran Program, Derek Klarin, Poornima Devineni, Anoop K Sendamarai, Anthony R Angueira, Sarah E Graham, Ying H Shen, Michael G Levin, James P Pirruccello, Ida Surakka, Purushotham R Karnam, Tanmoy Roychowdhury, Yanming Li, Minxian Wang, Krishna G Aragam, Kaavya Paruchuri, Verena Zuber, Gabrielle E Shakt, Noah L Tsao, Renae L Judy, Ha My T Vy, Shefali S Verma, Daniel J Rader, Ron Do, Joseph E Bavaria, Girish N Nadkarni, Marylyn D Ritchie, Stephen Burgess, Dong-Chuan Guo, Patrick T Ellinor, Scott A Lemaire, Dianna M Milewicz, Cristen J Willer, Pradeep Natarajan, Philip S Tsao, Saiju Pyarajan, Scott M Damrauer

Faculty, Staff and Student Publications

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and …

The Effects Of Obesity And Metabolic Abnormalities On Severe Covid-19-Related Outcomes After Vaccination: A Population-Based Study, Rebeca Kelly, Diego Aviles, Catriona Krisulevicz, Krystal Hunter, Lauren Krill, David Warshal, Olga Ostrovsky

Faculty, Staff and Student Publications

High mortality rates in ovarian cancer have been linked to recurrence, metastasis, and chemoresistant disease, which are known to involve not only genetic changes but also epigenetic aberrations. In ovarian cancer, adipose-derived stem cells from the omentum (O-ASCs) play a crucial role in supporting the tumor and its tumorigenic microenvironment, further propagating epigenetic abnormalities and dissemination of the disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we demonstrate the action of these diet-derived compounds in …

Remote Neuronal Activity Drives Glioma Progression Through Sema4f, Emmet Huang-Hobbs, Yi-Ting Cheng, Yeunjung Ko, Estefania Luna-Figueroa, Brittney Lozzi, Kathryn R Taylor, Malcolm Mcdonald, Peihao He, Hsiao-Chi Chen, Yuhui Yang, Ehson Maleki, Zhung-Fu Lee, Sanjana Murali, Michael R Williamson, Dongjoo Choi, Rachel Curry, James Bayley, Junsung Woo, Ali Jalali, Michelle Monje, Jeffrey L Noebels, Akdes Serin Harmanci, Ganesh Rao, Benjamin Deneen

Faculty, Staff and Students Publications

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform …

Evaluating Osteoarthritis Management Programs: Outcome Domain Recommendations From The Oarsi Joint Effort Initiative, K D Allen, K Huffman, R J Cleveland, M Van Der Esch, J H Abbott, A Abbott, K Bennell, J L Bowden, J Eyles, E L Healey, M A Holden, Prakash Jayakumar, K Koenig, G Lo, E Losina, K Miller, N Østerås, C Pratt, J G Quicke, S Sharma, S T Skou, A T Tveter, A Woolf, S P Yu, R S Hinman

Faculty, Staff and Students Publications

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA).

DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, …

Extracellular Vesicle-Packaged Ilk From Mesothelial Cells Promotes Fibroblast Activation In Peritoneal Fibrosis, Qiang Huang, Yuxiang Sun, Long Peng, Juan Sun, Zixin Sha, Hongchun Lin, Yongjie Li, Canming Li, Huiqun Li, Hongli Shang, Yanxu Chen, Xianrui Dou, Zhaoyong Hu, Zengchun Ye, Hui Peng

Faculty, Staff and Students Publications

Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long-term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell-cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single-cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD …

Autologous Humanized Pdx Modeling For Immuno-Oncology Recapitulates Features Of The Human Tumor Microenvironment, Michael Chiorazzi, Bradley Krasnick, Keenan J Robbins, Zachary Skidmore, Jacqueline Mudd, Ye Bi, S Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. …

Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan

2020-Current year OA Pubs

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition …

Defining The Full Spectrum Of Pediatric Firearm Injury And Death In The United States: It Is Even Worse Than We Think, Bindi J Naik-Mathuria, Cary M Cain, Elizabeth A Alore, Liang Chen, Lisa A Pompeii

Faculty, Staff and Students Publications

OBJECTIVE: To characterize the full spectrum of pediatric firearm injury in the United States by describing fatal and nonfatal injury data epidemiology, vulnerable populations, and temporal trends.

BACKGROUND: Firearm injury is the leading cause of death in children and adolescents in the United States. Nonfatal injury is critical to fully define the problem, yet accurate data at the national level are lacking.

METHODS: A cross-sectional study combining national firearm injury data from the Centers for Disease Control (fatal) and the National Trauma Data Bank (nonfatal) between 2008 and 2019 for ages 0 to 17 years. Data were analyzed using descriptive …

A Radiomics Model Based On Synthetic Mri Acquisition For Predicting Neoadjuvant Systemic Treatment Response In Triple-Negative Breast Cancer, Ken-Pin Hwang, Nabil A Elshafeey, Aikaterini Kotrotsou, Huiqin Chen, Jong Bum Son, Medine Boge, Rania M Mohamed, Abeer H Abdelhafez, Beatriz E Adrada, Bikash Panthi, Jia Sun, Benjamin C Musall, Shu Zhang, Rosalind P Candelaria, Jason B White, Elizabeth E Ravenberg, Debu Tripathy, Clinton Yam, Jennifer K Litton, Lei Huo, Alastair M Thompson, Peng Wei, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose

To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Materials and Methods

In this prospective study, 181 women diagnosed with stage I–III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting …

Pontocerebellar Hypoplasia Associated With Parg183trp Homozygous Variant In Exosc1 Gene: A Case Report, Nadirah S Damseh, Ali N Obeidat, Khondakar Sayef Ahammed, Motee Al-Ashhab, Motee Abu Awad, Ambro Van Hoof

Faculty, Staff and Student Publications

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and …