Medical Specialties Commons^™

Phase Ii Clinical Trial Of Axitinib And Avelumab In Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma, Renata Ferrarotto, Luana G Sousa, Lei Feng, Frank Mott, George Blumenschein, Mehmet Altan, Diana Bell, Flavia Bonini, Kaiyi Li, Mario L Marques-Piubelli, Eduardo A Dal Lago, Jason J Johnson, Yoshitsugu Mitani, Myrna Godoy, Anna Lee, Michael Kupferman, Ehab Hanna, Bonnie S Glisson, Yasir Elamin, Adel El-Naggar

Faculty, Staff and Student Publications

Purpose: We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).

Patients and methods: Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis.

Results: …

Magrolimab In Combination With Azacitidine In Patients With Higher-Risk Myelodysplastic Syndromes: Final Results Of A Phase Ib Study, David A Sallman, Monzr M Al Malki, Adam S Asch, Eunice S Wang, Joseph G Jurcic, Terrence J Bradley, Ian W Flinn, Daniel A Pollyea, Suman Kambhampati, Tiffany N Tanaka, Joshua F Zeidner, Guillermo Garcia-Manero, Deepa Jeyakumar, Rami Komrokji, Jeffrey Lancet, Hagop M Kantarjian, Lin Gu, Yajia Zhang, Anderson Tan, Mark Chao, Carol O'Hear, Giridharan Ramsingh, Indu Lal, Paresh Vyas, Naval G Daver

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week …

Efficacy Of A Smoking Cessation Intervention For Survivors Of Cervical Intraepithelial Neoplasia Or Cervical Cancer: A Randomized Controlled Trial, Jennifer I Vidrine, Steven K Sutton, David W Wetter, Ya-Chen Tina Shih, Lois M Ramondetta, Linda S Elting, Joan L Walker, Katie M Smith, Summer G Frank-Pearce, Yisheng Li, Sarah R Jones, Darla E Kendzor, Vani N Simmons, Damon J Vidrine

Faculty, Staff and Student Publications

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population.

METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) …

Insight Into The Desolvation Of Quaternary Ammonium Cation With Acetonitrile As A Solvent In Hydroxyl-Flat Pores: A First-Principles Calculation, Fudong Liu, Shaobin Yang, Xu Zhang, Shuwei Tang, Yingkai Xia

Faculty, Staff and Student Publications

Supercapacitors have a wide range of applications in high-technology fields. The desolvation of organic electrolyte cations affects the capacity size and conductivity of supercapacitors. However, few relevant studies have been published in this field. In this experiment, the adsorption behavior of porous carbon was simulated with first-principles calculations using a graphene bilayer with a layer spacing of 4-10 Å as a hydroxyl-flat pore model. The reaction energies of quaternary ammonium cations, acetonitrile, and quaternary ammonium cationic complexes were calculated in a graphene bilayer with different interlayer spacings, and the desolvation behavior of TEA+ and SBP+ ions was described. The critical …

Toll-Like Receptors 2, 4, And 9 Modulate Promoting Effect Of Copd-Like Airway Inflammation On K-Ras-Driven Lung Cancer Through Activation Of The Myd88/Nf-ĸb Pathway In The Airway Epithelium, Walter V Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T Grimaldo, Avantika Krishna, Michael J Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina De La Garza, Marco Ramos-Castaneda, Scott E Evans, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable

METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on …

Mitochondrial Replication Assay (Mira) For Efficient In Situ Quantification Of Nascent Mtdna And Protein Interactions With Nascent Mtdna (Mitosirf), Macy Lozen, Yue Chen, Rebecca A Boisvert, Katharina Schlacher

Faculty, Staff and Student Publications

Mitochondria play decisive roles in bioenergetics and intracellular communication. These organelles contain a circular mitochondrial DNA (mtDNA) genome that is duplicated within one to two hours by a mitochondrial replisome, independently from the nuclear replisome. mtDNA stability is regulated in part at the level of mtDNA replication. Consequently, mutations in mitochondrial replisome components result in mtDNA instability and are associated with diverse disease phenotypes, including premature aging, aberrant cellular energetics, and developmental defects. The mechanisms ensuring mtDNA replication stability are not completely understood. Thus, there remains a need to develop tools to specifically and quantifiably examine mtDNA replication. To date, …

Hiv-1 Transmission Among Injecting Drug Users Is Principally Derived From Local Circulating Strains In Guangxi, China, Ping Cen, Hua Yue Liang, Yuan Yang, Fei Zhang, Shi Xiong Yang, Ju Cong Mo, Yi Feng, Jie Gang Huang, Chuan Yi Ning, Chun Yuan Huang, Yao Yang, Na Liang, Bing Yu Liang, Li Ye, Hao Liang

Faculty, Staff and Student Publications

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission

METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.

RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Deepmicetl: A Deep Transfer Learning Based Prediction Of Mice Cardiac Conduction Diseases Using Early Electrocardiograms, Ying Liao, Yisha Xiang, Mingjie Zheng, Jun Wang

Faculty, Staff and Student Publications

Cardiac conduction disease is a major cause of morbidity and mortality worldwide. There is considerable clinical significance and an emerging need of early detection of these diseases for preventive treatment success before more severe arrhythmias occur. However, developing such early screening tools is challenging due to the lack of early electrocardiograms (ECGs) before symptoms occur in patients. Mouse models are widely used in cardiac arrhythmia research. The goal of this paper is to develop deep learning models to predict cardiac conduction diseases in mice using their early ECGs. We hypothesize that mutant mice present subtle abnormalities in their early ECGs …

Blockchain-Enabled Immutable, Distributed, And Highly Available Clinical Research Activity Logging System For Federated Covid-19 Data Analysis From Multiple Institutions, Tsung-Ting Kuo, Anh Pham, Maxim E Edelson, Jihoon Kim, Jason Chan, Yash Gupta, Lucila Ohno-Machado

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.

MATERIALS AND METHODS: We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain …

Joint Effect Of Human Papillomavirus Exposure, Smoking And Alcohol On Risk Of Oral Squamous Cell Carcinoma, Zheng Yang, Peng Sun, Kristina R Dahlstrom, Neil Gross, Guojun Li

Faculty, Staff and Students Publications

BACKGROUND: Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral squamous cell carcinoma (OSCC) including SCC of oropharynx (SCCOP) and SCC of oral cavity (SCCOC). Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. This study investigated the interactions among these risk factors and risk of OSCC.

METHODS: Totally 377 patients with newly diagnosed SCCOP and SCCOC and 433 frequency-matched cancer-free controls by age and sex were included. Multivariable logistic regression was performed to calculate ORs and 95% CIs.

RESULTS: We found that overall OSCC …

Whole-Exome Sequencing Study Of Hypospadias, Zhongzhong Chen, Yunping Lei, Richard H Finnell, Yu Ding, Zhixi Su, Yaping Wang, Hua Xie, Fang Chen

Faculty, Staff and Students Publications

Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology is still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in the etiology of severe hypospadias, as these genes are related to androgen signaling. Additionally, rare damaging variants in cilia-related outer dynein arm heavy chain (ODNAH) genes (DNAH5, DNAH8, DNAH9, DNAH11, and DNAH17) (p = 8.5 × 10−47) were significantly enriched in hypospadias cases. The Dnah8 KO mice exhibited significantly decreased testosterone levels, which had an impact on …

Mass Spectrometry Imaging Reveals Abnormalities In Cardiolipin Composition And Distribution In Astrocytoma Tumor Tissues, Anna C Krieger, Luis A Macias, J Clay Goodman, Jennifer S Brodbelt, Livia S Eberlin

Faculty, Staff and Students Publications

Cardiolipin (CL) is a mitochondrial lipid with diverse roles in cellular respiration, signaling, and organelle membrane structure. CL content and composition are essential for proper mitochondrial function. Deranged mitochondrial energy production and signaling are key components of glial cell cancers and altered CL molecular species have been observed in mouse brain glial cell xenograft tumors. The objective of this study was to describe CL structural diversity trends in human astrocytoma tumors of varying grades and correlate these trends with histological regions within the heterogeneous astrocytoma microenvironment. To this aim, we applied desorption electrospray ionization coupled with high field asymmetric ion …

Co-Delivery Of Therapeutics And Bioactive Gas Using A Novel Liposomal Platform For Enhanced Treatment Of Acute Arterial Injury, Shao-Ling Huang, Melanie R Moody, Xing Yin, David D Mcpherson, Hyunggun Kim

Faculty, Staff and Student Publications

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was …

Single-Frame Deep-Learning Super-Resolution Microscopy For Intracellular Dynamics Imaging, Rong Chen, Xiao Tang, Yuxuan Zhao, Zeyu Shen, Meng Zhang, Yusheng Shen, Tiantian Li, Casper Ho Yin Chung, Lijuan Zhang, Ji Wang, Binbin Cui, Peng Fei, Yusong Guo, Shengwang Du, Shuhuai Yao

Faculty, Staff and Student Publications

Single-molecule localization microscopy (SMLM) can be used to resolve subcellular structures and achieve a tenfold improvement in spatial resolution compared to that obtained by conventional fluorescence microscopy. However, the separation of single-molecule fluorescence events that requires thousands of frames dramatically increases the image acquisition time and phototoxicity, impeding the observation of instantaneous intracellular dynamics. Here we develop a deep-learning based single-frame super-resolution microscopy (SFSRM) method which utilizes a subpixel edge map and a multicomponent optimization strategy to guide the neural network to reconstruct a super-resolution image from a single frame of a diffraction-limited image. Under a tolerable signal density and …

Cxcl8/Cxcr2 Signaling Mediates Bone Marrow Fibrosis And Is A Therapeutic Target In Myelofibrosis, Andrew J Dunbar, Dongjoo Kim, Min Lu, Mirko Farina, Robert L Bowman, Julie L Yang, Young Park, Abdul Karzai, Wenbin Xiao, Zach Zaroogian, Kavi O'Connor, Shoron Mowla, Francesca Gobbo, Paola Verachi, Fabrizio Martelli, Giuseppe Sarli, Lijuan Xia, Nada Elmansy, Maria Kleppe, Zhuo Chen, Yang Xiao, Erin Mcgovern, Jenna Snyder, Aishwarya Krishnan, Corrine Hill, Keith Cordner, Anouar Zouak, Mohamed E Salama, Jayden Yohai, Eric Tucker, Jonathan Chen, Jing Zhou, Timothy Mcconnell, Anna R Migliaccio, Richard Koche, Raajit Rampal, Rong Fan, Ross L Levine, Ronald Hoffman

Faculty, Staff and Student Publications

Proinflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution are yet to be fully elucidated. Previously, we identified a critical role for combined constitutive JAK/STAT and aberrant NF-κB proinflammatory signaling in MF development. Using single-cell transcriptional and cytokine-secretion studies of primary cells from patients with MF and the human MPLW515L (hMPLW515L) murine model of MF, we extend our previous work and delineate the role of …

Pou4f1-Tbr1 Transcriptional Cascade Controls The Formation Of Jam2-Expressing Retinal Ganglion Cells, Takae Kiyama, Halit Y Altay, Tudor C Badea, Chai-An Mao

Faculty, Staff and Student Publications

More than 40 retinal ganglion cell (RGC) subtypes have been categorized in mouse based on their morphologies, functions, and molecular features. Among these diverse subtypes, orientation-selective Jam2-expressing RGCs (J-RGCs) has two unique morphologic characteristics: the ventral-facing dendritic arbor and the OFF-sublaminae stratified terminal dendrites in the inner plexiform layer. Previously, we have discovered that T-box transcription factor T-brain 1 (Tbr1) is expressed in J-RGCs. We further found that Tbr1 is essential for the expression of Jam2, and Tbr1 regulates the formation and the dendritic morphogenesis of J-RGCs. However, Tbr1 begins to express in terminally differentiated RGCs around …

Morphology Of The Ventral Process Of The Sixth Cervical Vertebra In Extinct And Extant Equus: Functional Implications, Sharon May-Davis, Robert Hunter, Richard White

Faculty, Staff and Student Publications

In this study, we examined the ventral process of C6 in extinct and extant Equus (sister taxa to Equus ferus caballus only) with the purpose of describing normal morphology and identifying anomalous variations relevant to recent studies describing a congenital malformation in E. ferus caballus. Overall, 83 specimens from 9 museums and 3 research/educational facilities were examined, totalling 71 extinct specimens from 12 species and 12 extant specimens from 5 species. The lateral view revealed that a large convexity exists in the ventral process between the cranial ventral tubercle (CrVT) and the caudal ventral tubercle (CVT) in the earliest …

Neutralizing Antibody Formation With Onabotulinumtoxina (Botox®) Treatment From Global Registration Studies Across Multiple Indications: A Meta-Analysis, Joseph Jankovic, Jean Carruthers, Markus Naumann, Patricia Ogilvie, Terry Boodhoo, Mayssa Attar, Swati Gupta, Ritu Singh, John Soliman, Irina Yushmanova, Mitchell F Brin, Jie Shen

Faculty, Staff and Students Publications

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and …

Deciphering Tumor Ecosystems At Super Resolution From Spatial Transcriptomics With Tesla, Jian Hu, Kyle Coleman, Daiwei Zhang, Edward B Lee, Humam Kadara, Linghua Wang, Mingyao Li

Faculty, Staff and Student Publications

Cell populations in the tumor microenvironment (TME), including their abundance, composition, and spatial location, are critical determinants of patient response to therapy. Recent advances in spatial transcriptomics (ST) have enabled the comprehensive characterization of gene expression in the TME. However, popular ST platforms, such as Visium, only measure expression in low-resolution spots and have large tissue areas that are not covered by any spots, which limits their usefulness in studying the detailed structure of TME. Here, we present TESLA, a machine learning framework for tissue annotation with pixel-level resolution in ST. TESLA integrates histological information with gene expression to annotate …

Correction: Combined Inhibition Of Bcl-2 And Mcl-1 Overcomes Bax Deficiency-Mediated Resistance Of Tp53-Mutant Acute Myeloid Leukemia To Individual Bh3 Mimetics, Bing Z Carter, Po Yee Mak, Wenjing Tao, Edward Ayoub, Lauren B Ostermann, Xuelin Huang, Sanam Loghavi, Steffen Boettcher, Yuki Nishida, Vivian Ruvolo, Paul E Hughes, Phuong K Morrow, Torsten Haferlach, Steven Kornblau, Muharrem Muftuoglu, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

Analysis Of Nurse And Patient Preferences For Pre-Filled Pen Devices For Self-Injection Of Highly Purified Human Menopausal Gonadotropin (Hp-Hmg, Menopur®), Guy De Mesmaeker, Brigitte Calles, Judith A Smith

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR

PATIENTS AND METHODS: This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection …

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Tp53 Germline Pathogenic Variant Frequency In Anaplastic Rhabdomyosarcoma: A Children’S Oncology Group Report, Douglas Fair, Luke Maese, Yueh-Yun Chi, Minjie Li, Douglas S Hawkins, Rajkumar Venkatramani, Erin Rudzinski, David Parham, Lisa Teot, David Malkin, Sharon E Plon, He Li, Aniko Sabo, Philip J Lupo, Joshua D Schiffman

Faculty, Staff and Students Publications

Rhabdomyosarcoma (RMS) is a well-described cancer in Li-Fraumeni syndrome, resulting from germline TP53 pathogenic variants (PVs). RMS exhibiting anaplasia (anRMS) are associated with a high rate of germline TP53 PVs. This study provides updated estimates of the prevalence of TP53 germline PVs in RMS (3%) and anRMS (11%) from a large cohort (n = 239) enrolled in five Children's Oncology Group (COG) clinical trials. Although the prevalence of germline TP53 PVs in patients with anRMS in this series is much lower than previously reported, this prevalence remains elevated. Germline evaluation for TP53 PVs should be strongly considered in patients with …

Sarcopenia And Cardiovascular Diseases, Abdulla A Damluji, Maha Alfaraidhy, Noora Alhajri, Namit N Rohant, Manish Kumar, Christina Al Malouf, Samira Bahrainy, Min Ji Kwak, Wayne B Batchelor, Daniel E Forman, Michael W Rich, James Kirkpatrick, Ashok Krishnaswami, Karen P Alexander, Gary Gerstenblith, Peggy Cawthon, Christopher R Defilippi, Parag Goyal

Faculty, Staff and Student Publications

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be …

From Bugs To Drugs: Bacterial 3-Iaa Enhances Efficacy Of Chemotherapy In Pancreatic Cancer, Y David Seo, Jennifer A Wargo

Faculty, Staff and Student Publications

Tintelnot et al. identified enrichment of indole-3-acetic acid (3-IAA), a tryptophan metabolite produced by gut microbiota, as a predictor of chemotherapy response in pancreatic adenocarcinoma. Recapitulated in mouse models, 3-IAA represents a novel potential therapeutic approach for chemotherapy sensitization.

Evaluation Of 89zr-Labeled Anti-Pd-L1 Monoclonal Antibodies Using Dfo And Novel Hopo Analogues As Chelating Agents For Immuno-Pet, Bhasker Radaram, Sarah E Glazer, Ping Yang, Chia-Wei Li, Mien-Chie Hung, Seth T Gammon, Mian Alauddin, David Piwnica-Worms

Faculty, Staff and Student Publications

Programmed death ligand 1 (PD-L1) is a type 1 transmembrane immunosuppressive protein that is expressed on a wide range of cell types, including cancer cells. Anti-PD-L1 antibodies have revolutionized cancer therapy and have led to improved outcomes for subsets of cancer patients, including triple-negative breast cancer (TNBC) patients. As a result, PET imaging of PD-L1 protein expression in cancer patients has been explored for noninvasive detection of PD-L1 expressing tumors as well as monitoring response to anti-PD-L1 immune checkpoint therapy. Previous studies have indicated that the in vivo stability and in vivo target detection of antibody-based radio-conjugates can be dramatically …

Break The "Hold": The Need To Strengthen The Management Of Hypertension, Obesity, Lipids, And Diabetes (Hold) And Improve Cardiovascular Health In People With Diabetes, Layla A Abushamat, Vijay Nambi

Faculty, Staff and Students Publications

No abstract provided.

Next-Generation Boron Drugs And Rational Translational Studies Driving The Revival Of Bnct, Danushka S Seneviratne, Omran Saifi, Yuri Mackeyev, Timothy Malouff, Sunil Krishnan

Faculty, Staff and Student Publications

BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT delivery. Given this, developing novel boronated compounds with high selectivity, ease of delivery, and large boron payloads remains an area of active investigation. Furthermore, there is growing interest in exploring the immunogenic potential of BNCT. In this review, we discuss the basic radiobiological and physical aspects of BNCT, traditional and next-generation boron compounds, as well as translational …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Ramesh Singh, Huan Meng, Tao Shen, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …