Medicine and Health Sciences Commons^™

Phase Ii Study Of Durvalumab (Anti-Pd-L1) And Trametinib (Meki) In Microsatellite Stable (Mss) Metastatic Colorectal Cancer (Mcrc), Benny Johnson, Cara L Haymaker, Edwin R Parra, Luisa Maren Solis Soto, Xuemei Wang, Jane V Thomas, Arvind Dasari, Van K Morris, Kanwal Raghav, Eduardo Vilar, Bryan K Kee, Cathy Eng, Christine M Parseghian, Robert A Wolff, Younghee Lee, Daniele Lorenzini, Caddie Laberiano-Fernandez, Anuj Verma, Wenhua Lang, Ignacio I Wistuba, Andrew Futreal, Scott Kopetz, Michael J Overman

Faculty, Staff and Student Publications

Background: Monotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells.

Methods: Open-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, …

Artificial Intelligence-Assisted Mapping Of Proliferation Centers Allows The Distinction Of Accelerated Phase From Large Cell Transformation In Chronic Lymphocytic Leukemia, Siba El Hussein, Pingjun Chen, L Jeffrey Medeiros, John D Hazle, Jia Wu, Joseph D Khoury

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is characterized morphologically by numerous small lymphocytes and pale nodules composed of prolymphocytes and paraimmunoblasts known as proliferation centers (PCs). Patients with CLL can undergo transformation to a more aggressive lymphoma, most often diffuse large B-cell lymphoma (DLBCL), known as Richter transformation (RT). An accelerated phase of CLL (aCLL) also may be observed which correlates with subsequent transformation to DLBCL, and may represent an early stage of transformation. Distinguishing PCs in CLL from aCLL or RT can be diagnostically challenging, particularly in small needle biopsy specimens. Available guidelines pertaining to distinguishing CLL from its' …

Exposure To Substance And Current Substance Among School-Going Adolescents In Timor-Leste, Abigail Esinam Adade, Kenneth Owusu Ansah, Nutifafa Eugene Yaw Dey, Francis Arthur-Holmes, Henry Ofori Duah, Pascal Agbadi

College of Nursing Faculty Research and Publications

Few studies have examined how exposure to substance influences adolescent’s use of substance in Timor-Leste. We assessed this relationship using nationally representative data from Timor-Leste to address this gap. Data was pulled from the 2015 Timor-Leste Global school-based student health survey. Data of students aged 13-17years (N = 3700) from class 7–11 across schools in Timor-Leste were analyzed for this study. Second-hand smoking exposure (AOR = 1.57 [1.31, 1.89] and parental tobacco use, AOR = 1.94 [1.54, 2.44]) was significantly related to in-school adolescent’s current use of substance after adjusting for covariates. Current substance use was also positively associated with …

Factors Associated With Initiation And Continuation Of Endocrine Therapy In Women With Hormone Receptor-Positive Breast Cancer, Beomyoung Cho, Maria Pérez, Donna B Jeffe, Matthew W Kreuter, Julie A Margenthaler, Graham A Colditz, Ying Liu

2020-Current year OA Pubs

BACKGROUND: Despite benefits of endocrine therapy (ET) for patients with hormone-receptor (HR)-positive breast cancer, many patients do not initiate or discontinue ET against recommendations.

METHODS: We identified variables associated with ET initiation and continuation, analyzing pooled data from two longitudinal studies at a National Cancer Institute comprehensive cancer center in St. Louis, Missouri. The sample included 533 women with newly diagnosed, non-metastatic, HR-positive breast cancer who completed interviews at enrollment and 6, 12, and 24 months after definitive surgical treatment. Logistic regression models estimated the adjusted odds ratio and 95% confidence interval (aOR [95% CI]) for each of self-reported ET …

Comparison Of Modern Periacetabular Osteotomy For Hip Dysplasia With Total Hip Arthroplasty For Hip Osteoarthritis-10-Year Outcomes Are Comparable In Young Adult Patients, Frank W Parilla, Serena Freiman, Gail E Pashos, Susan Thapa, John C Clohisy

2020-Current year OA Pubs

Young adult patients with symptomatic acetabular dysplasia and marginal secondary osteoarthritis can be faced with the decision to either undergo periacetabular osteotomy (PAO) to relieve symptoms and slow osteoarthritis progression or wait until progression to more advanced disease and undergo total hip arthroplasty (THA). The decision can be difficult, and contemporary literature to guide these decisions is sparse. Therefore, we retrospectively assessed complication rate, survivorship and patient-reported clinical outcomes [modified Harris Hip score (mHHS), UCLA Activity score] in two, consecutive cohorts of patients aged 18-40 years that underwent either PAO for symptomatic acetabular dysplasia (mean age 28.9 years) or THA …

Cardiovascular Complications Of Pregnancy-Associated Covid-19 Infections, Joan E Briller, Niti R Aggarwal, Melinda B Davis, Afshan B Hameed, Isabelle Malhamé, Zainab Mahmoud, Emily G Mcdonald, Glaucia Moraes De Oliveira, Odayme Quesada, Nandita S Scott, Jyoti Sharma, American College Of Cardiology Cardiovascular Disease In Women Committee

2020-Current year OA Pubs

Cardiovascular complications are frequently present in coronavirus-2019 (COVID-19) infection. These include microvascular and macrovascular thrombotic complications such as arterial and venous thromboembolism, myocardial injury or inflammation resulting in infarction, heart failure, and arrhythmias. Data suggest increased risk of adverse outcomes in pregnant compared with nonpregnant women of reproductive age with COVID-19 infection, including need for intensive care unit admission, mechanical ventilation, and extracorporeal membrane oxygenation utilization. Current statements addressing COVID-19-associated cardiac complications do not include pregnancy complications that may mimic COVID-19 complications such as peripartum cardiomyopathy, spontaneous coronary artery dissection, and preeclampsia. Unique to pregnancy, COVID-19 complications can result in …

Peptide-Sirna Nanoparticles Targeting Nf-Κb P50 Mitigate Experimental Abdominal Aortic Aneurysm Progression And Rupture, Huimin Yan, Ying Hu, Antonina Akk, Samuel A Wickline, Hua Pan, Christine T N Pham

2020-Current year OA Pubs

Abdominal aortic aneurysm (AAA) is a progressive vascular condition associated with high risk of mortality if left untreated. AAA is an inflammatory process with excessive local production of extracellular matrix degrading enzymes, leading to dilatation and rupture of the abdominal aorta. We posit that targeting NF-κB, a signaling pathway that controls inflammation, will halt AAA progression and prevent rupture. In an elastase-induced AAA model we observed that NF-κB activation increased progressively post-elastase perfusion. Unexpectedly, we found that AAA progression was marked by predominant nuclear accumulation of the NF-κB p50 subunit at the exclusion of p65. Using the amphipathic peptide p5RHH …

Plasma Metabolomics Analysis Of Aspirin Treatment And Risk Of Colorectal Adenomas, Elizabeth L Barry, Veronika Fedirko, Yutong Jin, Ken Liu, Leila A Mott, Janet L Peacock, Michael N Passarelli, John A Baron, Dean P Jones

Faculty, Staff and Student Publications

Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were …

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Brian A Van Tine, Et Al

2020-Current year OA Pubs

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression For Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series, Momodou L Jammeh, Alexander Yang, Ahmmad A Abuirqeba, J Westley Ohman, Robert W Thompson

2020-Current year OA Pubs

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge.

OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS.

METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively.

RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 …

Resting-State Functional Connectivity Identifies Individuals And Predicts Age In 8-To-26-Month-Olds, Omid Kardan, Sydney Kaplan, Muriah D. Wheelock, Dominique Meyer, Adam T. Eggebrecht, Christopher D. Smyser, Et Al.

2020-Current year OA Pubs

Resting-state functional connectivity (rsFC) measured with fMRI has been used to characterize functional brain maturation in typically and atypically developing children and adults. However, its reliability and utility for predicting development in infants and toddlers is less well understood. Here, we use fMRI data from the Baby Connectome Project study to measure the reliability and uniqueness of rsFC in infants and toddlers and predict age in this sample (8-to-26 months old; n = 170). We observed medium reliability for within-session infant rsFC in our sample, and found that individual infant and toddler's connectomes were sufficiently distinct for successful functional connectome …

Changes In Circulating Tumor Dna Reflect Clinical Benefit Across Multiple Studies Of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors, Diana Merino Vega, Aadel A Chaudhuri, Et Al

2020-Current year OA Pubs

PURPOSE: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.

PATIENTS AND METHODS: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell …

Nivolumab Plus Rucaparib For Metastatic Castration-Resistant Prostate Cancer: Results From The Phase 2 Checkmate 9kd Trial, Karim Fizazi, Margitta Retz, Daniel P Petrylak, Jeffrey C Goh, Jose Perez-Gracia, Louis Lacombe, Stefanie Zschäbitz, Mauricio Burotto, Hakim Mahammedi, Gwenaelle Gravis, Diogo Assed Bastos, Steven L Mccune, Juan Carlos Vázquez Limón, Edmond M Kwan, Daniel Castellano, Aude Fléchon, Fred Saad, Marc-Oliver Grimm, David R Shaffer, Andrew J Armstrong, Prabhu Bhagavatheeswaran, Neha P Amin, Keziban Ünsal-Kaçmaz, Xuya Wang, Jun Li, Andrea Loehr, Russell K Pachynski

2020-Current year OA Pubs

BACKGROUND: CheckMate 9KD (NCT03338790) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib.

METHODS: CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 …

Robustness And Reproducibility Of An Artificial Intelligence-Assisted Online Segmentation And Adaptive Planning Process For Online Adaptive Radiation Therapy, John W Chapman, Dao Lam, Bin Cai, Geoffrey D Hugo

2020-Current year OA Pubs

Clinical implementation of online adaptive radiation therapy requires initial and ongoing performance assessment of the underlying auto-segmentation and adaptive planning algorithms, although a straightforward and efficient process for this in phantom is lacking. The purpose of this work was to investigate robustness and repeatability of the artificial intelligence-assisted online segmentation and adaptive planning process on the Varian Ethos adaptive platform, and to develop an end-to-end test strategy for online adaptive radiation therapy. Five synthetic deformations were generated and applied to a computed tomography image of an anthropomorphic pelvis phantom, and reference treatment plans were generated from each of the resulting …

Comparison Of Endoscopic Underlay And Over-Under Tympanoplasty Techniques For Type I Tympanoplasty, James W Bao, Kevin Y Zhan, Cameron C Wick

2020-Current year OA Pubs

Objective: To compare the indications and efficacy of endoscopic over-under tympanoplasty versus endoscopic underlay tympanoplasty.

Methods: Retrospective cohort study of patients undergoing type I endoscopic tympanoplasty via either an underlay or over-under technique by a single surgeon from 2017 to 2021. Patients were excluded if they had a concurrent mastoidectomy, ossiculoplasty, or advanced cholesteatoma defined by involvement of multiple subsites. Patient demographics, perforation size and location, middle ear status, preoperative and postoperative audiograms, and perforation closure were reviewed. Middle ear status was represented using the Ossiculoplasty Outcome Parameter Score (OOPS). The primary outcome was perforation closure at most recent follow-up …

Dysosteosclerosis: Clinical And Radiological Evolution Reflecting Genetic Heterogeneity, Serap Turan, Steven Mumm, Ceren Alavanda, Betul Sare Kaygusuz, Busra Gurpinar Tosun, Ahmet Arman, Margaret Huskey, Tulay Guran, Shenghui Duan, Abdullah Bereket, Michael P Whyte

2020-Current year OA Pubs

Dysosteosclerosis (DSS), the term coined in 1968 for ultrarare dysplasia of the skeleton featuring platyspondyly with focal appendicular osteosclerosis, has become generic by encompassing the genetic heterogeneity recently reported for this phenotype. We studied four unrelated Turkish patients with DSS to advance understanding of the new nosology. Patient 1 suffered femur fractures beginning at age 1 year. DSS was suspected from marked metaphyseal osteosclerosis in early childhood and subsequently platyspondyly accompanying patchy osteosclerosis of her appendicular skeleton. She harbored in

Impaired Mitophagy In Sanfilippo A Mice Causes Hypertriglyceridemia And Brown Adipose Tissue Activation, Miguel Tillo, Patricia I Dickson, Et Al.

2020-Current year OA Pubs

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency and heparan sulfate storage on energy homeostasis and metabolism in a mouse model of type IIIa mucopolysaccharidosis (MPS IIIa, Sanfilippo A syndrome). At 12-weeks of age, MPS IIIa mice exhibited fasting and postprandial hypertriglyceridemia compared with wildtype mice, with a reduction of white and brown adipose tissues. Partitioning of dietary [

Fetal Loss In Pregnant Rhesus Macaques Infected With High-Dose African-Lineage Zika Virus, Lauren E. Raasch, Kevin K. Noguchi, Nicole A. Fuhler, Et Al

2020-Current year OA Pubs

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant …

Comparative Proteomics Of Adult Paragonimus Kellicotti Excretion/Secretion Products Released In Vitro Or Present In The Lung Cyst Nodule, Lucia S. Di Maggio, Kurt C. Curtis, Petra Erdmann-Gilmore, Robert S. W. Sprung, R. Reid Townsend, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

Paragonimus kellicotti is a zoonotic lung fluke infection, the agent of North American paragonimiasis, and an excellent model for other Paragonimus infections. The excretory/secretory proteins (ESP) released by parasites and presented at the parasite-host interface are frequently proposed to be useful targets for drugs and/or vaccines In vitro culture conditions may alter ESP compared to those produced in vivo. In order to investigate ESPs produced in vivo we took advantage of the fact that adult P. kellicotti reproduce in the lungs of experimentally infected gerbils in tissue cysts. We performed a mass-spectrometric analysis of adult P. kellicotti soluble somatic protein …

Difference Imaging From Single Measurements In Diffuse Optical Tomography: A Deep Learning Approach, Shuying Li, Menghao Zhang, Minghao Xue, Quing Zhu

2020-Current year OA Pubs

SIGNIFICANCE: "Difference imaging," which reconstructs target optical properties using measurements with and without target information, is often used in diffuse optical tomography (DOT) in vivo imaging. However, taking additional reference measurements is time consuming, and mismatches between the target medium and the reference medium can cause inaccurate reconstruction.

AIM: We aim to streamline the data acquisition and mitigate the mismatch problems in DOT difference imaging using a deep learning-based approach to generate data from target measurements only.

APPROACH: We train an artificial neural network to output data for difference imaging from target measurements only. The model is trained and validated …

Depression, Stigma And Social Isolation: The Psychosocial Trifecta Of Primary Chronic Cutaneous Lupus Erythematosus, A Cross-Sectional And Path Analysis, Cristina Drenkard, Kristina A Theis, Timothy T Daugherty, Charles G Helmick, Charmayne Dunlop-Thomas, Gaobin Bao, Laura Aspey, Tené T Lewis, S Sam Lim

2020-Current year OA Pubs

OBJECTIVE: Depression is common in individuals with chronic cutaneous lupus erythematosus (CCLE). However, how CCLE may impact patients' psychological well-being is poorly understood, particularly among disproportionally affected populations. We examined the relationships between depression and psychosocial factors in a cohort of predominantly Black patients with primary CCLE (CCLE without systemic manifestations).

METHODS: Cross-sectional assessment of individuals with dermatologist-validated diagnosis of primary CCLE. NIH-PROMIS short-forms were used to measure depression, disease-related stigma, social isolation and emotional support. Linear regression analyses (ɑ=0.05) were used to test an a priori conceptual model of the relationship between stigma and depression and the effect of …

Snmmi/Acr/Asnc/Scmr Joint Credentialing Statement For Cardiac Pet/Mri: Endorsed By The American Heart Association, Terrence D Ruddy, Mouaz Al-Mallah, James A Arrighi, John P Bois, David A Bluemke, Marcelo F Di Carli, Vasken Dilsizian, Robert J Gropler, Hossein Jadvar, Saurabh Malhotra, Matthier Pelletier-Galarneau, Thomas H Schindler, Pamela K Woodard, Panithaya Chareonthaitawee

2020-Current year OA Pubs

No abstract provided.

Association Of Endocrine Therapy Initiation Timeliness With Adherence And Continuation In Low-Income Women With Breast Cancer, Nikita Sood, Ying Liu, Min Lian, Tracy Greever-Rice, Jill Lucht, Chester Schmaltz, Graham A Colditz

2020-Current year OA Pubs

Importance: Though adjuvant endocrine therapy (AET) has proven efficacy in treating hormone receptor-positive (HR-positive) breast cancer, patient adherence to AET and continuation of treatment as recommended by guidelines remain suboptimal, especially for low-income patients.

Objective: To quantify timelines for initiating AET and assess their association with short- and long-term adherence and continuation of AET in low-income women with breast cancer.

Design, Setting, and Participants: This population-based retrospective cohort study included women younger than 65 years diagnosed with first primary HR-positive breast cancer between January 1, 2007, and December 31, 2013, followed up for 5 years after the first use of …

Patient Preferences For Strategies To Improve Tuberculosis Diagnostic Services In Zambia, Andrew D Kerkhoff, Lophina Chilukutu, Sarah Nyangu, Mary Kagujje, Kondwelani Mateyo, Nsala Sanjase, Ingrid Eshun-Wilson, Elvin H Geng, Diane V Havlir, Monde Muyoyeta

2020-Current year OA Pubs

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.

Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.

Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was …

Phase I Trial Of The Dll3/Cd3 Bispecific T-Cell Engager Bi 764532 In Dll3-Positive Small-Cell Lung Cancer And Neuroendocrine Carcinomas, Martin Wermke, Enriqueta Felip, Valentina Gambardella, Yasutoshi Kuboki, Daniel Morgensztern, Zohra Oum' Hamed, Meiruo Liu, Matus Studeny, Taofeek K Owonikoko

2020-Current year OA Pubs

Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 …

Frontline Polatuzumab Vedotin For Diffuse Large B-Cell Lymphoma: A Survey Of Clinician Impressions, Ajay Major, Edward R Scheffer Cliff, Daniel A Ermann, Urshila Durani, David A Russler-Germain

2020-Current year OA Pubs

In the POLARIX trial, pola-R-CHP demonstrated improved progression-free survival (PFS) compared to R-CHOP in untreated intermediate- to high-risk DLBCL. We surveyed practicing clinicians regarding their interpretation of POLARIX, including impressions of efficacy, safety, and cost. Of 174 respondents, most from academic centers (82%) in the United States (57%), 70% stated they would not replace R-CHOP with pola-R-CHP due to insufficient PFS difference, lack of overall survival benefit, and excessive cost. Respondents not recommending pola-R-CHP expressed concerns about financial implications for both society and patients. We observed considerable heterogeneity in both study interpretation and plans for real-world implementation of pola-R-CHP.

Il-34 Deficiency Impairs Foxp3+ Treg Function In A Model Of Autoimmune Colitis And Decreases Immune Tolerance Homeostasis, Antoine Freuchet, Marco Colonna, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8

METHODS: We generated Il34

RESULTS: Here we report that the absence of expression of IL-34 in Il34

CONCLUSION: Altogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4

HIGHLIGHTS: -Absence of expression of IL-34 in Il34

A Multidimensional Metabolomics Workflow To Image Biodistribution And Evaluate Pharmacodynamics In Adult Zebrafish, Madelyn M Jackstadt, Casey A Chamberlain, Steven R Doonan, Leah P Shriver, Gary J Patti

2020-Current year OA Pubs

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. …

Ovario Phase Ii Trial Of Combination Niraparib Plus Bevacizumab Maintenance Therapy In Advanced Ovarian Cancer Following First-Line Platinum-Based Chemotherapy With Bevacizumab., Melissa M Hardesty, Thomas C Krivak, Gail S Wright, Erika Hamilton, Evelyn L Fleming, Jimmy Belotte, Erika K Keeton, Ping Wang, Divya Gupta, Aine Clements, Heidi J Gray, Gottfried E Konecny, Richard G Moore, Debra L Richardson

Oncology Articles

OBJECTIVE: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.

METHODS: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety.

RESULTS: Among …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …