Biomedical Informatics Commons^™

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E Colbert, Molly B El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J Lynn, Timothy A Harris, Jacob H Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K Bronk, Julie Sammouri, Ananta V Yanamandra, Adilene V Olvera, Lily G Carlin, Travis Sims, Andrea Y Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O Abana, Hannah X Li, Patricia J Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M Ramondetta, Andrew M Futreal, Kathleen M Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J Ajami, Matthew Wong, Cullen Taniguchi, Joseph F Petrosino, K Jagannadha Sastry, Pablo C Okhuysen, Sara A Martinez, Lin Tan, Iqbal Mahmud, Philip L Lorenzi, Jennifer A Wargo, Ann H Klopp

Faculty, Staff and Student Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

Faculty, Staff and Student Publications

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …

Microplastics In Different Tissues Of A Commonly Consumed Fish, Mohammad Belal Hossain, Farjana Haque Pingki, Md Abdus Samad Azad, As-Ad Ujjaman Nur, Partho Banik, Bilal Ahamad Paray, Takaomi Arai, Jimmy Yu

Faculty, Staff and Student Publications

Microplastics (MPs) ingestion by fish signifies a worldwide threat to human health but limited research has examined their existence within the consumable portions (muscle) of fish. Thus, this study was undertaken to unveil the prevalence, characterization, and contamination extent of MPs across various body tissues, including the muscle of the king mackerel (S. guttatus) from the lower Meghna estuary in Bangladesh-a pioneering investigation in this region. In our analysis, we identified a total of 487 MPs, with an average abundance of 48.7 ± 20.3 MPs/individual. These MPs were distributed across different tissues, with respective concentrations of 0.84 ± …

Single-Cell Analysis Differentiates The Effects Of P53 Mutation And P53 Loss On Cell Compositions Of Oncogenic Kras-Driven Pancreatic Cancer, Xinlei Sun, Daowei Yang, Yang Chen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (KrasG12D), in combination with either p53 mutation by knock-in strategy (Trp53R172H) or p53 loss by conditional knockout (Trp53cKO) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between KrasG12D; Trp53R172H (KPmut) mouse models and KrasG12D; Trp53cKO (KPloss) mouse models …

The Importance Of A Healthy Microbiome In Pregnancy And Infancy And Microbiota Treatment To Reverse Dysbiosis For Improved Health, Herbert L Dupont, Madeleine Mary Hines Salge

Faculty, Staff and Student Publications

BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during …

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

A Longitudinal Study Of Polygenic Score And Cognitive Function Decline Considering Baseline Cognitive Function, Lifestyle Behaviors, And Diabetes Among Middle-Aged And Older Us Adults, Tingting Liu, Changwei Li, Ruiyuan Zhang, Eugenia Flores Millender, Hongyu Miao, Michael Ormsbee, Jinzhen Guo, Adrianna Westbrook, Yang Pan, Jing Wang, Tanika N Kelly

Faculty, Staff and Student Publications

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment.

Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 …

Recurrent Somatic Copy Number Alterations And Their Association With Oncogene Expression Levels In High-Grade Ovarian Serous Carcinoma, Hillary P Esplen, Richard K Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L Jeffrey Medeiros, Gokce A Toruner

Faculty, Staff and Student Publications

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly …

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Cd46-Adc Reduces The Engraftment Of Multiple Myeloma Patient-Derived Xenografts, Michael J Vanwyngarden, Zachary J Walker, Yang Su, Olivia Perez De Acha, Brett M Stevens, Peter A Forsberg, Tomer M Mark, William Matsui, Bin Liu, Daniel W Sherbenou

Faculty, Staff and Student Publications

An antibody-drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46-ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by …

Is The Direct Fixation Of Displaced Quadrilateral Plates In Acetabular Fractures Necessary?, Beom-Soo Kim, Ki-Cheor Bae, Chul-Hyun Cho, Kyung-Jae Lee, In Gyu Lee, Min-Gyu Lee, Byung-Woo Min

Faculty, Staff and Student Publications

Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of …

Venetoclax Abrogates The Prognostic Impact Of Splicing Factor Gene Mutations In Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Samuel Urrutia, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Abhishek Maiti, Hussein A Abbas, Naval G Daver, Naveen Pemmaraju, Sherry Pierce, Kelly S Chien, Koji Sasaki, Tapan M Kadia, Danielle E Hammond, Gautam Borthakur, Keyur Patel, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Courtney D Dinardo

Faculty, Staff and Student Publications

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P …

Voltage- And Calcium-Gated Membrane Currents Tune The Plateau Potential Properties Of Multiple Neuron Types, Curtis L Neveu, Paul Smolen, Douglas A Baxter, John H Byrne

Faculty, Staff and Student Publications

Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau potentials that, once elicited, can lead to prolonged activity that is independent of stimulus intensity or duration. To better understand this diversity of information processing, we compared the voltage-gated and Ca2+-gated currents of three identified neurons from hermaphroditic Aplysia californica Two of these neurons, B51 and B64, generated plateau potentials and a third neuron, B8, exhibited regular firing and was incapable of generating a plateau potential. With the exception of the Ca2+-gated potassium current (I KCa), all …

The Cancer Moonshot Immuno-Oncology Translational Network At 5: Accelerating Cancer Immunotherapies, Ananth Annapragada, Andrew G Sikora, Himangi Marathe, Song Liu, Michael Demetriou, Lawrence Fong, Jinming Gao, Donald Kufe, Zachary S Morris, Eduardo Vilar, Elad Sharon, Alan Hutson, Kunle Odunsi

Faculty, Staff and Student Publications

The Immuno-Oncology Translational Network (IOTN) was established in 2018 as part of the Cancer Moonshot. In 2022, President Joe Biden set new goals to reduce the cancer death rate by half within 25 years and improve the lives of people with cancer and cancer survivors. The IOTN is focused on accelerating translation of cancer immunology research, from bench to bedside, and improving immunotherapy outcomes across a wide array of cancers in the adult population. The unique structure and team science approach of the IOTN is designed to accelerate discovery and evaluation of novel immune-based therapeutic and prevention strategies. In this …

Synthetic Megavoltage Cone Beam Computed Tomography Image Generation For Improved Contouring Accuracy Of Cardiac Pacemakers, Hana Baroudi, Xinru Chen, Wenhua Cao, Mohammad D El Basha, Skylar Gay, Mary Peters Gronberg, Soleil Hernandez, Kai Huang, Zaphanlene Kaffey, Adam D Melancon, Raymond P Mumme, Carlos Sjogreen, January Y Tsai, Cenji Yu, Laurence E Court, Ramiro Pino, Yao Zhao

Faculty, Staff and Student Publications

In this study, we aimed to enhance the contouring accuracy of cardiac pacemakers by improving their visualization using deep learning models to predict MV CBCT images based on kV CT or CBCT images. Ten pacemakers and four thorax phantoms were included, creating a total of 35 combinations. Each combination was imaged on a Varian Halcyon (kV/MV CBCT images) and Siemens SOMATOM CT scanner (kV CT images). Two generative adversarial network (GAN)-based models, cycleGAN and conditional GAN (cGAN), were trained to generate synthetic MV (sMV) CBCT images from kV CT/CBCT images using twenty-eight datasets (80%). The pacemakers in the sMV CBCT …

Comparison Of Single-Port Laparoscopy With Other Surgical Approaches In Endometrial Cancer Surgical Staging: Propensity-Score-Matched Analysis, Sang Hyun Cho, Jung-Yun Lee, Eun Ji Nam, Sunghoon Kim, Young Tae Kim, Sang Wun Kim

Faculty, Staff and Student Publications

This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared …

Author Correction: Regulation Of Hnrnpa1 By Micrornas Controls The Mir-18a-K-Ras Axis In Chemotherapy-Resistant Ovarian Cancer, Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

No abstract provided.

Counts, Incidence Rates, And Trends Of Pediatric Cancer In The United States, 2003–2019, David A Siegel, Jessica B King, Philip J Lupo, Eric B Durbin, Eric Tai, Kathi Mills, Elizabeth Van Dyne, Natasha Buchanan Lunsford, S Jane Henley, Reda J Wilson

Faculty, Staff and Students Publications

BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available.

METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents younger than 20 years of age diagnosed with malignant tumors between 2003 and 2019. We calculated the average annual percent change (APC) and APC using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type.

RESULTS: With …

A Single Cell Genomics Atlas Of The Drosophila Larval Eye Reveals Distinct Photoreceptor Developmental Timelines, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The Drosophila eye is a powerful model system to study the dynamics of cell differentiation, cell state transitions, cell maturation, and pattern formation. However, a high-resolution single cell genomics resource that accurately profiles all major cell types of the larval eye disc and their spatiotemporal relationships is lacking. Here, we report transcriptomic and chromatin accessibility data for all known cell types in the developing eye. Photoreceptors appear as strands of cells that represent their dynamic developmental timelines. As photoreceptor subtypes mature, they appear to assume a common transcriptomic profile that is dominated by genes involved in axon function. We identify …

Rotational Symmetry Breaking In Superconducting Nickelate Nd08sr02nio2 Films, Haoran Ji, Yi Liu, Yanan Li, Xiang Ding, Zheyuan Xie, Chengcheng Ji, Shichao Qi, Xiaoyue Gao, Minghui Xu, Peng Gao, Liang Qiao, Yi-Feng Yang, Guang-Ming Zhang, Jian Wang

Faculty, Staff and Student Publications

The infinite-layer nickelates, isostructural to the high-Tc cuprate superconductors, have emerged as a promising platform to host unconventional superconductivity and stimulated growing interest in the condensed matter community. Despite considerable attention, the superconducting pairing symmetry of the nickelate superconductors, the fundamental characteristic of a superconducting state, is still under debate. Moreover, the strong electronic correlation in the nickelates may give rise to a rich phase diagram, where the underlying interplay between the superconductivity and other emerging quantum states with broken symmetry is awaiting exploration. Here, we study the angular dependence of the transport properties of the infinite-layer nickelate Nd0.8Sr0.2NiO2 superconducting …

Efficacy Of Sotagliflozin In Adults With Type 2 Diabetes In Relation To Baseline Hemoglobin A1c, Rahul Aggarwal, Deepak L Bhatt, Michael Szarek, Christopher P Cannon, Darren K Mcguire, Silvio E Inzucchi, Renato D Lopes, Michael J Davies, Phillip Banks, Bertram Pitt, Philippe Gabriel Steg

Faculty, Staff and Student Publications

Background: The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.

Objectives: We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.

Methods: We included all adults from SCORED and SOLOIST-WHF. The primary …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

Ischemic Bowel Associated With Newly Diagnosed Patent Foramen Ovale, Hannah Hong, Deanna Glassman, Shannon Neville Westin

Faculty, Staff and Student Publications

No abstract provided.

The Deubiquitinase Zranb1 Is An E3 Ubiquitin Ligase For Slc7a11 And Regulates Ferroptotic Resistance, Shan Huang, Qimin Zhang, Manyu Zhao, Xing Wang, Yilei Zhang, Boyi Gan, Peijing Zhang

Faculty, Staff and Student Publications

The dependency of cancer cells on iron increases their susceptibility to ferroptosis, thus providing new opportunities for patients with treatment-resistant tumors. However, we show that lipid peroxidation, a hallmark of ferroptosis, was found in various areas of patient samples, indicating the potential resistance of ferroptosis. Using whole deubiquitinases (DUBs) sgRNA screening, we found that loss of ZRANB1 confers cancer cell resistance to ferroptosis. Intriguingly, functional studies revealed that ZRANB1 ubiquitinates and represses SLC7A11 expression as an E3 ubiquitin ligase and that ZRANB1 inhibits glutathione (GSH) synthesis through SLC7A11 degradation, leading to elevated lipid peroxidation and ferroptosis. Deletion of the region …

Aptamers As Potential Therapeutic Tools For Ovarian Cancer: Advancements And Challenges, Wojciech Szymanowski, Anna Szymanowska, Anna Bielawska, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo, Paola Amero

Faculty, Staff and Student Publications

Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug …

Identification Of Blood Protein Biomarkers Associated With Prostate Cancer Risk Using Genetic Prediction Models: Analysis Of Over 140,000 Subjects, Hua Zhong, Jingjing Zhu, Shuai Liu, Dalia H Ghoneim, Praveen Surendran, Tao Liu, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Herbert Yu, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant …

Repurposing Egfr Inhibitors For Oral Cancer Pain And Opioid Tolerance, Maria Daniela Santi, Morgan Zhang, Naijiang Liu, Chi T Viet, Tongxin Xie, Dane D Jensen, Moran Amit, Huilin Pan, Yi Ye

Faculty, Staff and Student Publications

Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how …

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …

Language Nativeness Modulates Physiological Responses To Moral Vs Immoral Concepts In Chinese-English Bilinguals: Evidence From Event-Related Potential And Psychophysiological Measures, Fei Gao, Chenggang Wu, Hengyi Fu, Kunyu Xu, Zhen Yuan

Faculty, Staff and Student Publications

Morality has been an integral part of social cognition and our daily life, and different languages may exert distinct impacts on human moral judgment. However, it remains unclear how moral concept is encoded in the bilingual brain. This study, therefore, aimed to explore the emotional and cognitive involvement of bilingual morality judgement by using combined event-related potential (ERP) and psychophysiological (including skin, heart, and pulse) measures. In the experiment, thirty-one Chinese-English bilingual participants were asked to make moral judgments in Chinese and English, respectively. Our results revealed increased early frontal N400 and decreased LPC in L1 moral concept encoding as …