Medical Specialties Commons^™

Rejection Resistant Cd30car-Modified Epstein-Barr Virus-Specific T Cells As An Off-The-Shelf Platform For Cd30+ Lymphoma, David H Quach, Haran R Ganesh, Yolanda D Briones, Nazila Nouraee, Audrey Ma, Yezan F Hadidi, Sandhya Sharma, Cliona M Rooney

Faculty, Staff and Students Publications

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. …

Integration Of Ζ-Deficient Cars Into The Cd3Ζ Gene Conveys Potent Cytotoxicity In T And Nk Cells, Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-El-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L Wagner

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) …

Erratum: Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Changes In Plasma Concentrations Of Per- And Polyfluoroalkyl Substances After Bariatric Surgery In Adolescents From The Teen-Longitudinal Assessment Of Bariatric Surgery (Teen-Labs) Study, Brittney O Baumert, Sandrah P Eckel, Jesse A Goodrich, Zhenjiang Li, Nikos Stratakis, Douglas I Walker, Yinqi Zhao, Fabian Christoph Fischer, Scott Bartell, Damaskini Valvi, Xiangping Lin, Zoe Coates Fuentes, Thomas Inge, Justin Ryder, Todd Jenkins, Rohit Kohli, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate …

Understanding Enterprise Data Warehouses To Support Clinical And Translational Research: Impact, Sustainability, Demand Management, And Accessibility, Thomas R Campion, Catherine K Craven, David A Dorr, Elmer V Bernstam, Boyd M Knosp

Faculty, Staff and Student Publications

OBJECTIVES: Healthcare organizations, including Clinical and Translational Science Awards (CTSA) hubs funded by the National Institutes of Health, seek to enable secondary use of electronic health record (EHR) data through an enterprise data warehouse for research (EDW4R), but optimal approaches are unknown. In this qualitative study, our goal was to understand EDW4R impact, sustainability, demand management, and accessibility.

MATERIALS AND METHODS: We engaged a convenience sample of informatics leaders from CTSA hubs (n = 21) for semi-structured interviews and completed a directed content analysis of interview transcripts.

RESULTS: EDW4R have created institutional capacity for single- and multi-center studies, democratized access …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Sensory Asic3 Channel Exacerbates Psoriatic Inflammation Via A Neurogenic Pathway In Female Mice, Chen Huang, Pei-Yi Sun, Yiming Jiang, Yuandong Liu, Zhichao Liu, Shao-Ling Han, Bao-Shan Wang, Yong-Xin Huang, An-Ran Ren, Jian-Fei Lu, Qin Jiang, Ying Li, Michael X Zhu, Zhirong Yao, Yang Tian, Xin Qi, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated …

An Incidentally Found Mass On The Remnant Stomach After A Roux-En-Y Gastric Bypass, Jennifer E. Geller, Santosh Swaminathan, Kristin Noonan

Abington Jefferson Health Papers

BACKGROUND: Incidentally found masses are a widely discussed area of medicine, and there are conflicting opinions as to how to deal with these findings, particularly in the stomach-which has limited documentation in the literature. Here we present a middle-aged female who was found to have an incidentally found mass on her remnant stomach 10 years after a Roux-en-Y gastric bypass (RYGB) surgery.

CASE PRESENTATION: We present the case of a 66-year-old female who is 10 years post-op from a RYGB. After a bout of self-resolving diarrheal illness prompted a computed tomography (CT) scan in the emergency department, she was diagnosed …

Stepping Into The Light: Defining Culprit Lesion In Non-St Elevation Myocardial Infarction, Aditya Doni Pradana M.D., M.Sc, Arditya Damarkusuma M.D., M.Med (Clin Epi), Fiha, Hariadi Hariawan M.D., Fiha, Finasim, Dr., Fica, Fascc, Fapsic, Fscai

Journal of the Saudi Heart Association

Identifying the infarct-related artery (IRA) in a non-ST-segment-elevation acute myocardial infarction (NSTEMI) can be very challenging, particularly in a hospital that cannot perform intracoronary imaging due to certain limitations. This is because, by angiography, most patients present with multivessel coronary artery disease (CAD), diffuse disease, or non-significant CAD. We present a case of a 60-year-old female patient presented with substernal chest pain and palpitations of 6 hours duration. The first hospital contacts 12-lead electrocardiogram (ECG) showed ventricular tachycardia (VT) with unstable hemodynamics, after stabilization patient was transported to the catheterization laboratory for immediate percutaneous coronary intervention (PCI). With a clue …

Incidence, Risk Factors And Outcomes Of Acute Kidney Injury In Neonates Undergoing Open-Heart Surgeries: Single Center Experience, Faisal A. Alghamdi, Mohammed A. Bin Mahfooz, Hatim F. Almutairi, Nasser S. Alshaiban, Khaled E. Alotibi, Omar M. Kabbani, Mohamed S. Kabbani

Journal of the Saudi Heart Association

Background: Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the incidence, risk factors, and outcome of AKI among neonates undergoing open-heart surgery. Methods: This is a retrospective cohort study between 2016 and 2021 for all neonates requiring open heart surgery. The cases were divided into 2 groups: the AKI (index) group and the non-AKI (control) group. The two groups were statistically compared for risk factors, needs for dialysis, and outcomes. Results: 100 patients fulfilled the inclusion criteria. Among them, 74 (74%) developed AKI, …

What Are The Lessons Learned From A Survivorship Trial During The Pandemic?, Alanna J. Horowitz, Sharneet J. Sandhu, Sherry J. Guo, Gabriel Barreto-D'Silva, Leonardo Barreto-D'Silva, Krishna Gunturu

The Lahey Journal

Purpose: The American Cancer Society (ACS) has acknowledged the importance of maintaining a healthy diet and engaging in regular physical activity for cancer survivors. While studies have found that adherence to these guidelines improves long-term quality of life, several studies showed that up to 70% of cancer survivors do not meet the standards. The purpose of this pilot study is to determine the effectiveness of a multi-disciplinary survivorship clinic (MDSC) in helping patients adhere to the ACS survivorship guidelines and its impacts on quality of life (QOL).

Methods: Primary objective of the study is to encourage cancer patients to adhere …

Effects Of A 10-Week Footstrike Transition Programme On Tibial Stress Fracture Probability; A Randomized Controlled Intervention Using Finite Element And Probabilistic Modelling, Jonathan Sinclair, Paul J. Taylor

Baltic Journal of Health and Physical Activity

Introduction: The aim of this study was to undertake a randomized control trial examining the effects of a 10-week footstrike transition program on tibial stress fracture risk compared to control. Material and methods: Twenty habitual rearfoot strike runners were randomly assigned to either footstrike or control groups. The footstrike group undertook a graduated 10-week program which allowed them to convert their habitual rearfoot strike pattern, whereas the control group maintained their normal training regime without any alterations to their strike pattern. Running biomechanics were collected using an eight-camera motion capture system, and ground reaction forces using a force plate. Tibial …

Metformin In Systemic Lupus Erythematosus: Investigating Cardiovascular Impact And Nephroprotective Effects In Lupus Nephritis, Yurilu A. Gonzalez Moret, Kevin Bryan Lo, Irene J. Tan

Einstein Health Papers

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE.

METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory …

Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre

Faculty, Staff and Student Publications

This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al. address current gaps and strategies needed in research, policy, and technology, offering a road map for stakeholders.

Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo

Faculty, Staff and Student Publications

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …

Case Report: Dementia Sensitivity To Altitude Changes And Effective Treatment With Hyperbaric Air And Glutathione Precursors, Edward F. Fogarty, Paul G. Harch

School of Medicine Faculty Publications

A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and …

The Glucosylamine Oxidation Pathway Of Vitamin C Recycling, James M. Hempe, Daniel S. Hsia, Arthur Hagar, Larry Byers

School of Medicine Faculty Publications

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP …

To Revise Or Not Revise? Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma, Victoria S. Wu, Henry J. Stitzel, John B. Ammori, Jeffrey Hardacre, Lee M. Ocuin

Faculty Scholarship

Background: The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. Methods: Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010–2020) and those who underwent pancreatectomy at the authors’ institution (2010–2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). Results: The study included 225 patients from the authors’ institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the …

A Single Cell Rna Sequence Atlas Of The Early Drosophila Larval Eye, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The Drosophila eye has been an important model to understand principles of differentiation, proliferation, apoptosis and tissue morphogenesis. However, a single cell RNA sequence resource that captures gene expression dynamics from the initiation of differentiation to the specification of different cell types in the larval eye disc is lacking. Here, we report transcriptomic data from 13,000 cells that cover six developmental stages of the larval eye. Our data show cell clusters that correspond to all major cell types present in the eye disc ranging from the initiation of the morphogenetic furrow to the differentiation of each photoreceptor cell type as …

Leveraging Integrated Rna Sequencing To Decipher Adrenomedullin's Protective Mechanisms In Experimental Bronchopulmonary Dysplasia, Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L Grimm, Cristian Coarfa, Fabian Theis, Lukas M Simon, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/−) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency …

Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.

Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …

Editorial For "Parallel Cnn-Deep Learning Clinical-Imaging Signature For Assessing Pathologic Grade And Prognosis Of Soft Tissue Sarcoma Patients", Pegah Khosravi

Publications and Research

No abstract provided.

Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

Identifying Overdose Risk Factors For People Hospitalized With Injection Drug Use-Associated Infections In Maine, Melanie Mait, Kim Murray, Tania D. Strout, Kinna Thakarar

Journal of Maine Medical Center

Introduction: The overdose crisis continues to be a significant problem, particularly in rural states such as Maine. The objectives of this study were to: 1) describe demographic and health characteristics and 2) identify overdose risk factors among people in Maine hospitalized with injection drug use (IDU)-associated infections.

Methods: We performed descriptive analysis of demographics, health characteristics, and injection practices, stratified by lifetime history of overdose. We conducted an exploratory logistic regression analysis, controlling for gender, homelessness, having experienced an emergency department (ED) visit in the past 3-months, and endorsement of injecting alone in the past 30 days to examine …

Let’S Go! 2022-2023 Educational Programs: Developing A Standardized Obesity Medicine Curriculum Through A Realist Evaluation, Isaac Stickney, Peter Amann, Victoria Rogers, Austin Steward, Kayla Bronzo, Alec Luro, Robert Bing-You

Journal of Maine Medical Center

Problem: Obesity is linked to more than 200 chronic conditions, lower quality of life, and worse outcomes for patients. Let’s Go! is a community engagement initiative that works with communities to create environments that support healthy behaviors that impact obesity. Let’s Go! provides educational programming for all medical learners and providers throughout Maine and Carroll County, New Hampshire. The goal of Let’s Go! is to address the health outcomes of obesity and the stigma associated with it, including its impact on patients’ mental health and clinicians’ unconscious biases.

Approach: We used a realist evaluation, a framework in which the social …

Effects Of Exercise Or Metformin On Myokine Concentrations In Patients With Breast And Colorectal Cancer: A Phase Ii Multi-Centre Factorial Randomized Trial, Justin C. Brown, Guillaume Spielmann, Shengping Yang, Stephanie L.E. Compton, Lee W. Jones, Melinda L. Irwin, Jennifer A. Ligibel, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were …

Phase 2 Study Of Neoadjuvant Enzalutamide And Paclitaxel For Luminal Androgen Receptor-Enriched Tnbc: Trial Results And Insights Into “Arness”, Bora Lim, Sahil Seth, Clinton Yam, Lei Huo, Takeo Fujii, Jangsoon Lee, Roland Bassett, Sara Nasser, Lisa Ravenberg, Jason White, Alyson Clayborn, Gil Guerra, Jennifer K Litton, Senthil Damodaran, Rachel Layman, Vicente Valero, Debasish Tripathy, Michael Lewis, Lacey E Dobrolecki, Jonathan Lei, Rosalind Candelaria, Banu Arun, Gaiane Rauch, Li Zhao, Jianhua Zhang, Qingqing Ding, W Fraser Symmans, Jeffrey T Chang, Alastair M Thompson, Stacy L Moulder, Naoto T Ueno

Faculty, Staff and Student Publications

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a …

Sod1 Is A Synthetic-Lethal Target In Ppm1d-Mutant Leukemia Cells, Linda Zhang, Joanne I Hsu, Etienne D Braekeleer, Chun-Wei Chen, Tajhal D Patel, Alejandra G Martell, Anna G Guzman, Katharina Wohlan, Sarah M Waldvogel, Hidetaka Uryu, Ayala Tovy, Elsa Callen, Rebecca L Murdaugh, Rosemary Richard, Sandra Jansen, Lisenka Vissers, Bert B A De Vries, Andre Nussenzweig, Shixia Huang, Cristian Coarfa, Jamie Anastas, Koichi Takahashi, George Vassiliou, Margaret A Goodell

Faculty, Staff and Student Publications

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg2+/Mn2+-dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our …

Does The Use Of Double Hormone Replacement Therapy For Trauma Patient Organ Donors Improve Organ Recovery For Transplant, Eden M. Gallegos, Tanner Reed, Paige Deville, Blake Platt, Claudia Leonardi, Lillian Bellfi, Jessica Dufrene, Saad Chaudhary, John Hunt, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alan Marr, Anil Paramesh, Alison A. Smith

School of Graduate Studies Faculty Publications

BACKGROUND With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS A retrospective review …