Medical Specialties Commons^™

Mass Spectrometry Based Biomarkers For Early Detection Of Hcc Using A Glycoproteomic Approach, Yehia Mechref, Wenjing Peng, Sakshi Gautam, Parisa Ahmadi, Yu Lin, Jianhui Zhu, Jie Zhang, Suyu Liu, Amit G Singal, Neehar D Parikh, David M Lubman

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%-90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Jo A Rinaudo, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

A Comparative Analysis Of Radical Cystectomy With Perioperative Chemotherapy, Chemoradiation Therapy, Or Systemic Therapy In Patients With Clinically Advanced Node-Positive Bladder Cancer (Cn2/N3), Harshit Garg, Mukund Bhandari, Furkan Dursun, Michael A Liss, Dharam Kaushik, Robert S Svatek, Ahmed M Mansour

Faculty, Staff and Student Publications

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.

Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND …

Editorial: Women In Molecular And Cellular Oncology, Petranel T Ferrao, Laura Rosanò, Valeria Poli, Shilpa S Dhar, Ana Paula Lepique

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Women In Molecular And Cellular Oncology, Volume Ii: 2022, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …

Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans

Faculty, Staff and Student Publications

No abstract provided.

Epigenetic Aging In Psychiatry: Clinical Implications And Therapeutic Opportunities, Camila N C Lima, Gabriel R Fries

Faculty, Staff and Student Publications

No abstract provided.

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Kevin Diao, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

Global Research Trends And Prospects Related To Tumor Microenvironment Within Triple Negative Breast Cancer: A Bibliometric Analysis, Peiting Li, Jun Li, Xiaofei Tong, Zhenyang Xiao, Wuliang Diao, Chi Zhong, Jianda Zhou, Wei Wu

Faculty, Staff and Student Publications

Background and aims: The tumor microenvironment (TME) has pivotal parts within multiple tumor models of onset/progression, such as triple-negative breast cancer (TNBC). This bibliometric analysis was developed to explore trends and research niches revolving around TME in TNBC.

Methods: Web of Science Core Collection was queried for identifying studies linked with TME in TNBC, after which the VOSviewer, CiteSpace, and R software programs were used to conduct bibliometric analyses and to generate corresponding visualizations.

Results: In total, this study included 1,604 studies published from 2005-2023. The USA and China exhibited the highest numbers of citations, and the research institutions with …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

The Assembled Genome Of The Stroke-Prone Spontaneously Hypertensive Rat, Theodore S Kalbfleisch, Nahla A Hussien Abouel Ela, Kai Li, Wesley A Brashear, Kelli J Kochan, Andrew E Hillhouse, Yaming Zhu, Isha S Dhande, Eric J Kline, Elizabeth A Hudson, Terence D Murphy, Françoise Thibaud-Nissen, Melissa L Smith, Peter A Doris

Faculty, Staff and Student Publications

BACKGROUND: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease.

METHODS: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Frontostriatal And Limbic Contributions To Cognitive Decline In Parkinson’S Disease, Gregory Brown, Jonathan Hakun, Mechelle M Lewis, Sol De Jesus, Guangwei Du, Paul J Eslinger, Lan Kong, Xuemei Huang

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD.

METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models …

Molecular Predictors Of Immunophenotypic Measurable Residual Disease Clearance In Acute Myeloid Leukemia, Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A Patel, Sheng F Cai, Linde A Miles, Robert L Bowman, Mark B Geyer, Andrew Dunbar, Zachary D Epstein-Peterson, Erin Mcgovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Eytan M Stein, Bartlomiej Getta, Maria E Arcila, Qi Gao, Juliet Barker, Brian C Shaffer, Esperanza B Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L Levine, Sergio A Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S Tallman, Mikhail Roshal, Aaron D Goldberg

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and …

Combining Mek And Src Inhibitors For Treatment Of Colorectal Cancer Demonstrate Increased Efficacy In Vitro But Not In Vivo, Fan Fan, Susmita Ghosh, Reid Powell, Jason Roszik, Yongsun Park, Mary Sobieski, Alexey Sorokin, Clifford Stephan, Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Metastatic colorectal cancer (mCRC) is the second leading cause of cancer deaths in the United States. More than 50% of patients with mCRC harbor mutations of the oncogenic driver RAS (KRAS or NRAS). Because directly targeting most mutations of RAS is technically challenging, researchers have concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK as single-agent therapy is ineffective in patients with mCRC. We hypothesize that combining a MEK inhibitor with other agents can enhance the efficacy of MEK targeting in mCRC. Unbiased high-throughput screening (HTS) was performed to identify drugs that enhance the efficacy of MEK …

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Validation Of An Automated Contouring And Treatment Planning Tool For Pediatric Craniospinal Radiation Therapy, Soleil Hernandez, Hester Burger, Callistus Nguyen, Arnold C Paulino, John T Lucas, Austin M Faught, Jack Duryea, Tucker Netherton, Dong Joo Rhee, Carlos Cardenas, Rebecca Howell, David Fuentes, Julianne Pollard-Larkin, Laurence Court, Jeannette Parkes

Faculty, Staff and Student Publications

PURPOSE: Treatment planning for craniospinal irradiation (CSI) is complex and time-consuming, especially for resource-constrained centers. To alleviate demanding workflows, we successfully automated the pediatric CSI planning pipeline in previous work. In this work, we validated our CSI autosegmentation and autoplanning tool on a large dataset from St. Jude Children's Research Hospital.

METHODS: Sixty-three CSI patient CT scans were involved in the study. Pre-planning scripts were used to automatically verify anatomical compatibility with the autoplanning tool. The autoplanning pipeline generated 15 contours and a composite CSI treatment plan for each of the compatible test patients (n=51). Plan quality was evaluated quantitatively …

Effects Of Heterozygous Deletion Of Autism-Related Gene Cullin-3 In Mice, Qiang-Qiang Xia, Angela K Walker, Chenghui Song, Jing Wang, Anju Singh, James A Mobley, Zhong X Xuan, Jeffrey D Singer, Craig M Powell

Faculty, Staff and Student Publications

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area …

Editorial: Ovarian Cancer-Targeted Medication: Parp Inhibitors, Anti-Angiogenic Drugs, Immunotherapy, And More, Zhi-Bin Wang, Dan Liu, Guang Lei, Zhao-Qian Liu, Nayiyuan Wu, Jing Wang

Faculty, Staff and Student Publications

No abstract provided.

Pseudohypoadrenalism, A Subclinical Cortisol Metabolism Disorder In Hyperuricemia, Ruixia Bao, Beibei Chen, Jujie Pan, Alexander Wang, Haiyang Yu, Qian Chen, Yi Zhang, Tao Wang

Faculty, Staff and Student Publications

Background: Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.

Methods: The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.

Results: In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and …

Mri And Amino Acid Pet Detection Of Whole-Brain Tumor Burden, Peng Chen, Matthew L Scarpelli, Debbie R Healey, Shwetal Mehta, C Chad Quarles

Faculty, Staff and Student Publications

Background: [18F]fluciclovine amino acid PET has shown promise for detecting brain tumor regions undetected on conventional anatomic MRI scans. However, it remains unclear which of these modalities provides a better assessment of the whole brain tumor burden. This study quantifies the performance of [18F]fluciclovine PET and MRI for detecting the whole brain tumor burden.

Methods: Thirteen rats were orthotopically implanted with fluorescently transduced human glioblastoma cells. Rats underwent MRI (T1- and T2-weighted) and [18F]fluciclovine PET. Next brains were excised, optically cleared, and scanned ex vivo with fluorescence imaging. All images were co-registered using a novel landmark-based registration to enable a …

A Cross-Sectional Study To Test Equivalence Of Low- Versus Intermediate-Flip Angle Dynamic Susceptibility Contrast Mri Measures Of Relative Cerebral Blood Volume In Patients With High-Grade Gliomas At 15 Tesla Field Strength, Mark S Shiroishi, Dane Weinert, Steven Y Cen, Bino Varghese, Timothy Dondlinger, Melissa Prah, Jesse Mendoza, Sina Nazemi, Nima Ameli, Negin Amini, Salman Shohas, Shannon Chen, Bavrina Bigjahan, Gabriel Zada, Thomas Chen, Josh Neman-Ebrahim, Eric L Chang, Frances E Chow, Zhaoyang Fan, Wensha Yang, Frank J Attenello, Jason Ye, Paul E Kim, Vishal N Patel, Alexander Lerner, Jay Acharya, Leland S Hu, C Chad Quarles, Jerrold L Boxerman, Ona Wu, Kathleen M Schmainda

Faculty, Staff and Student Publications

INTRODUCTION: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) …

Current Chemoprevention Approaches In Lynch Syndrome And Familial Adenomatous Polyposis: A Global Clinical Practice Survey, Kathryn A Mraz, Rachel Hodan, Linda Rodgers-Fouche, Sanjeevani Arora, Francesc Balaguer, Jose G Guillem, Joanne M Jeter, Priyanka Kanth, Dan Li, David Liska, Joshua Melson, Kimberly Perez, Charite Ricker, Brian H Shirts, Eduardo Vilar, Bryson W Katona, Mev Dominguez-Valentin

Faculty, Staff and Student Publications

Background: International chemoprevention preferences and approaches in Lynch syndrome (LS) and APC-associated polyposis, including Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) have not been previously explored.

Aim: To describe current chemoprevention strategies for patients with LS or FAP/AFAP (referred to collectively as FAP) practiced by members of four international hereditary cancer societies through administration of a survey.

Results: Ninety-six participants across four hereditary gastrointestinal cancer societies responded to the survey. Most respondents (91%, 87/96) completed information regarding their demographics and practice characteristics relating to hereditary gastrointestinal cancer and chemoprevention clinical practices. Sixty-nine percent (60/87) of respondents offer chemoprevention …

Complex I Inhibitor Of Oxidative Phosphorylation In Advanced Solid Tumors And Acute Myeloid Leukemia: Phase I Trials, Timothy A Yap, Naval Daver, Mikhila Mahendra, Jixiang Zhang, Carlos Kamiya-Matsuoka, Funda Meric-Bernstam, Hagop M Kantarjian, Farhad Ravandi, Meghan E Collins, Maria Emilia Di Francesco, Ecaterina E Dumbrava, Siqing Fu, Sisi Gao, Jason P Gay, Sonal Gera, Jing Han, David S Hong, Elias J Jabbour, Zhenlin Ju, Daniel D Karp, Alessia Lodi, Jennifer R Molina, Natalia Baran, Aung Naing, Maro Ohanian, Shubham Pant, Naveen Pemmaraju, Prithviraj Bose, Sarina A Piha-Paul, Jordi Rodon, Carolina Salguero, Koji Sasaki, Anand K Singh, Vivek Subbiah, Apostolia M Tsimberidou, Quanyun A Xu, Musa Yilmaz, Qi Zhang, Yuan Li, Christopher A Bristow, Meenakshi B Bhattacharjee, Stefano Tiziani, Timothy P Heffernan, Christopher P Vellano, Philip Jones, Cobi J Heijnen, Annemieke Kavelaars, Joseph R Marszalek, Marina Konopleva

Faculty, Staff and Student Publications

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759. The PK, PD, and preliminary antitumor activities of IACS-010759 in patients were also evaluated as secondary endpoints in both clinical trials. IACS-010759 had a narrow …

Glucocorticoid Mediated Inhibition Of Lkb1 Mutant Non-Small Cell Lung Cancers, Kenneth E Huffman, Long Shan Li, Ryan Carstens, Hyunsil Park, Luc Girard, Kimberley Avila, Shuguang Wei, Rahul Kollipara, Brenda Timmons, Jessica Sudderth, Nawal Bendris, Jiyeon Kim, Pamela Villalobos, Junya Fujimoto, Sandra Schmid, Ralph J Deberardinis, Ignacio Wistuba, John Heymach, Ralf Kittler, Esra A Akbay, Bruce Posner, Yuzhuo Wang, Stephen Lam, Steven A Kliewer, David J Mangelsdorf, John D Minna

Faculty, Staff and Student Publications

The glucocorticoid receptor (GR) is an important anti-cancer target in lymphoid cancers but has been understudied in solid tumors like lung cancer, although glucocorticoids are often given with chemotherapy regimens to mitigate side effects. Here, we identify a dexamethasone-GR mediated anti-cancer response in a subset of aggressive non-small cell lung cancers (NSCLCs) that harbor Serine/Threonine Kinase 11 (STK11/LKB1) mutations. High tumor expression of carbamoyl phosphate synthase 1 (CPS1) was strongly linked to the presence of LKB1 mutations, was the best predictor of NSCLC dexamethasone (DEX) sensitivity (

Predictive Power Of Deep-Learning Segmentation Based Prognostication Model In Non-Small Cell Lung Cancer, Jordan C Gainey, Yusen He, Robert Zhu, Stephen S Baek, Xiaodong Wu, John M Buatti, Bryan G Allen, Brian J Smith, Yusung Kim

Faculty, Staff and Student Publications

Purpose: The study aims to create a model to predict survival outcomes for non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT) using deep-learning segmentation based prognostication (DESEP).

Methods: The DESEP model was trained using imaging from 108 patients with NSCLC with various clinical stages and treatment histories. The model generated predictions based on unsupervised features learned by a deep-segmentation network from computed tomography imaging to categorize patients into high and low risk groups for overall survival (DESEP-predicted-OS), disease specific survival (DESEP-predicted-DSS), and local progression free survival (DESEP-predicted-LPFS). Serial assessments were also performed using auto-segmentation based volumetric …

Feasibility Of Quantitative Diffusion-Weighted Imaging During Intra-Procedural Mri-Guided Brachytherapy Of Locally Advanced Cervical And Vaginal Cancers, Megan C Jacobsen, Bastien Rigaud, Samantha J Simiele, Gaiane M Rauch, Matthew S Ning, Sastry Vedam, Ann H Klopp, R Jason Stafford, Kristy K Brock, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Purpose: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI).

Methods and materials: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were …

Predictive Capacity Of A Mirna Panel In Identifying Teratoma In Post-Chemotherapy Consolidation Surgeries, Joseph A Moore, Michael J Lehner, Simone Anfossi, Saumil Datar, Rebecca S Tidwell, Matthew Campbell, Amishi Y Shah, John F Ward, Jose A Karam, Christopher G Wood, Lois L Pisters, George A Calin, Shi-Ming Tu

Faculty, Staff and Student Publications

OBJECTIVES: To investigate the utility of a novel serum miRNA biomarker panel to distinguish teratoma from nonmalignant necrotic/fibrotic tissues or nonviable tumours in patients with NSGCT undergoing post-chemotherapy consolidation surgery.

PATIENTS AND METHODS: We prospectively collected pre-surgical serum samples from 22 consecutive testicular NSGCT patients with residual NSGCT after chemotherapy undergoing post-chemotherapy consolidation surgery. We measured serum miRNA expression of four microRNAs (miRNA-375, miRNA-200a-3p, miRNA-200a-5p and miRNA-200b-3p) and compared with pathologic findings at time of surgery. Receiver operating characteristic (ROC) curves were performed to assess the ability of these miRNA to differentiate between teratoma and necrosis or viable malignancy.

RESULTS: …