Biomedical Informatics Commons^™

Predictive Digital Twin For Optimizing Patient-Specific Radiotherapy Regimens Under Uncertainty In High-Grade Gliomas, Anirban Chaudhuri, Graham Pash, David A Hormuth, Guillermo Lorenzo, Michael Kapteyn, Chengyue Wu, Ernesto A B F Lima, Thomas E Yankeelov, Karen Willcox

Faculty, Staff and Student Publications

We develop a methodology to create data-driven predictive digital twins for optimal risk-aware clinical decision-making. We illustrate the methodology as an enabler for an anticipatory personalized treatment that accounts for uncertainties in the underlying tumor biology in high-grade gliomas, where heterogeneity in the response to standard-of-care (SOC) radiotherapy contributes to sub-optimal patient outcomes. The digital twin is initialized through prior distributions derived from population-level clinical data in the literature for a mechanistic model's parameters. Then the digital twin is personalized using Bayesian model calibration for assimilating patient-specific magnetic resonance imaging data. The calibrated digital twin is used to propose optimal …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Bingzhou Guo, Ziwei Liu, Yafei Wu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

Acute Myeloid Leukemia With Concurrent Npm1 And Runx1 Mutations, Zhuang Zuo, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

NPM1 mutation, as a founding genetic event, cooperates with other gene mutations, such as DNMT3A and FLT3, to promote the development of acute myeloid leukemia. NPM1 mutation, however, has been reported to be mutually exclusive with RUNX1 mutation in acute myeloid leukemia cases. In this study, we analyzed mutation panel testing data from a relatively large cohort of rare AML cases with both NPM1 and RUNX1 mutations. We describe the dynamic process of the emergence of these mutations, as well as molecular genetic features and clinical outcome of these patients. We show that concurrence of both mutations in acute …

Integrated Clinical Genotype-Phenotype Characteristics Of Early T-Cell Precursor Acute Lymphoblastic Leukemia, Matthew T Ye, Yi Wang, Zhuang Zuo, Steliana Calin, Hua He, Zhenya Tang, Elias J Jabbour, Gautam Borthakur, Yizhuo Zhang, Yaling Yang, M James You

Faculty, Staff and Student Publications

Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a unique immunophenotype and high treatment failure rate. The molecular genetic abnormalities and their prognostic impact in ETP-ALL patients are poorly understood.

Methods: The authors performed systematic analyses of the clinicopathologic features with an emphasis on molecular genetic aspects of 32 patients with ETP-ALL.

Results: The median age was 43 years (range, 16-71). The blasts were positive for cytoplasmic CD3 and CD7 and negative for CD1a and CD8. Other markers expressed included CD34 (88%), CD33 (72%), CD117 (68%), CD13 (58%), CD5 (partial, 56%), CD2 (38%), …

Ribonuclease 1 Enhances Antitumor Immunity Against Breast Cancer By Boosting T Cell Activation, Ying-Nai Wang, Heng-Huan Lee, Zhou Jiang, Li-Chuan Chan, Gabriel N Hortobagyi, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

The secretory enzyme human ribonuclease 1 (RNase1) is involved in innate immunity and anti-inflammation, achieving host defense and anti-cancer effects; however, whether RNase1 contributes to adaptive immune response in the tumor microenvironment (TME) remains unclear. Here, we established a syngeneic immunocompetent mouse model in breast cancer and demonstrated that ectopic RNase1 expression significantly inhibited tumor progression. Overall changes in immunological profiles in the mouse tumors were analyzed by mass cytometry and showed that the RNase1-expressing tumor cells significantly induced CD4+ Th1 and Th17 cells and natural killer cells and reduced granulocytic myeloid-derived suppressor cells, supporting that RNase1 favors an antitumor …

Naproxen Chemoprevention Induces Proliferation Of Cytotoxic Lymphocytes In Lynch Syndrome Colorectal Mucosa, Charles M Bowen, Nan Deng, Laura Reyes-Uribe, Edwin Roger Parra, Pedro Rocha, Luisa M Solis, Ignacio I Wistuba, Valerie O Sepeda, Lana Vornik, Marjorie Perloff, Eva Szabo, Asad Umar, Krishna M Sinha, Powel H Brown, Eduardo Vilar

Faculty, Staff and Student Publications

BACKGROUND: Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.

METHODS: Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled 'Naproxen Study' were obtained and subjected to a tissue microarray for image mass cytometry …

Membranous Nephropathy In Chronic Lymphocytic Leukemia Responsive To Ibrutinib: A Case Report, Anna-Eve Turcotte, William F Glass, Jamie S Lin, Jan A Burger

Faculty, Staff and Student Publications

Membranous nephropathy (MN) is an uncommon renal presentation in patients with chronic lymphocytic leukemia (CLL), and as such, there is no standard therapy for these patients. A few cases of MN in CLL have been described with varying success in MN treatment involving alkylating agents and fludarabine. Here we report the first case of MN in a patient with CLL treated with ibrutinib with complete renal response. This presentation underlines the importance of recognizing rare glomerular diseases that may occur with CLL and offers a new therapeutic avenue to the treatment of CLL-associated MN.

Distinct Patterns Of Auto-Reactive Antibodies Associated With Organ-Specific Immune-Related Adverse Events, Mehmet Altan, Quan-Zhen Li, Qi Wang, Natalie I Vokes, Ajay Sheshadri, Jianjun Gao, Chengsong Zhu, Hai T Tran, Saumil Gandhi, Mara B Antonoff, Stephen Swisher, Jing Wang, Lauren A Byers, Noha Abdel-Wahab, Maria C Franco-Vega, Yinghong Wang, J Jack Lee, Jianjun Zhang, John V Heymach

Faculty, Staff and Student Publications

UNLABELLED: The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were …

A Scientific Communication Mentoring Intervention Benefits Diverse Mentees With Language Variety Related Discomfort, Carrie A Cameron, Hwa Young Lee, Cheryl B Anderson, Erin K Dahlstrom, Shine Chang

Faculty, Staff and Student Publications

We studied social-psychological effects over time of a faculty-mentor workshop intervention that addressed attitudes associated with language variety and their impact on scientific communication (SC) skill development of PhD and postdoctoral STEM research trainees (N = 274). Six months after their mentors attended the workshop, all mentees had significant gains in productivity in speaking tasks. In particular, mentees with high language discomfort rated their quality of communication with their mentor and their enthusiasm about communicating more highly (p < .05 for both measures), compared to mentees with low language discomfort. In addition, mentees raised speaking nonstandardized varieties of English reported significant reductions in discomfort related to language use (p = .003), compared to mentees raised speaking standardized English. We conclude that training mentors to understand and respond to …

Comparison Of Pharmacological Inhibitors Of Lysine-Specific Demethylase 1 In Glioblastoma Stem Cells Reveals Inhibitor-Specific Efficacy Profiles, Lea M Stitzlein, Achintyan Gangadharan, Leslie M Walsh, Deokhwa Nam, Alexsandra B Espejo, Melissa M Singh, Kareena H Patel, Yue Lu, Xiaoping Su, Ravesanker Ezhilarasan, Joy Gumin, Sanjay Singh, Erik Sulman, Frederick F Lang, Joya Chandra

Faculty, Staff and Student Publications

INTRODUCTION: Improved therapies for glioblastoma (GBM) are desperately needed and require preclinical evaluation in models that capture tumor heterogeneity and intrinsic resistance seen in patients. Epigenetic alterations have been well documented in GBM and lysine-specific demethylase 1 (LSD1/KDM1A) is amongst the chromatin modifiers implicated in stem cell maintenance, growth and differentiation. Pharmacological inhibition of LSD1 is clinically relevant, with numerous compounds in various phases of preclinical and clinical development, but an evaluation and comparison of LSD1 inhibitors in patient-derived GBM models is lacking.

METHODS: To assess concordance between knockdown of LSD1 and inhibition of LSD1 using a prototype inhibitor in …

Immune Checkpoint Inhibitors In Advanced Cutaneous Squamous Cell Carcinoma: A Systemic Review And Meta-Analysis, Haoran Zhang, Ai Zhong, Junjie Chen

Faculty, Staff and Student Publications

BACKGROUND: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC).

MATERIALS AND METHODS: A meta-analysis was conducted, and the efficacy and safety of CPI were assessed.

RESULTS: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%.

CONCLUSIONS: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.

Text Classification Of Cancer Clinical Trial Eligibility Criteria, Yumeng Yang, Soumya Jayaraj, Ethan Ludmir, Kirk Roberts

Faculty, Staff and Student Publications

Automatic identification of clinical trials for which a patient is eligible is complicated by the fact that trial eligibility are stated in natural language. A potential solution to this problem is to employ text classification methods for common types of eligibility criteria. In this study, we focus on seven common exclusion criteria in cancer trials: prior malignancy, human immunodeficiency virus, hepatitis B, hepatitis C, psychiatric illness, drug/substance abuse, and autoimmune illness. Our dataset consists of 764 phase III cancer trials with these exclusions annotated at the trial level. We experiment with common transformer models as well as a new pre-trained …

Sart-3 Functions To Regulate Germline Sex Determination In C Elegans, Tokiko Furuta, Swathi Arur

Faculty, Staff and Student Publications

Caenorhabditis elegans gene sart-3 was first identified as the homolog of human SART3 ( S quamous cell carcinoma A ntigen R ecognized by T -cells 3). In humans, expression of SART3 is associated with squamous cell carcinoma, thus most of the studies focus on its potential role as a target of cancer immunotherapy (Shichijo et al. 1998; Yang et al. 1999). Furthermore, SART3 is also known as Tip110 (Liu et al. 2002; Whitmill et al. 2016) in the context of HIV virus host activation pathway. Despite these disease related studies, the molecular function of this protein was not revealed until …

Optimization Of Mesh Generation For Geometric Accuracy, Robustness, And Efficiency Of Biomechanical-Model-Based Deformable Image Registration, Yulun He, Brian M Anderson, Guillaume Cazoulat, Bastien Rigaud, Lusmeralis Almodovar-Abreu, Julianne Pollard-Larkin, Peter Balter, Zhongxing Liao, Radhe Mohan, Bruno Odisio, Stina Svensson, Kristy K Brock

Faculty, Staff and Student Publications

BACKGROUND: Successful generation of biomechanical-model-based deformable image registration (BM-DIR) relies on user-defined parameters that dictate surface mesh quality. The trial-and-error process to determine the optimal parameters can be labor-intensive and hinder DIR efficiency and clinical workflow.

PURPOSE: To identify optimal parameters in surface mesh generation as boundary conditions for a BM-DIR in longitudinal liver and lung CT images to facilitate streamlined image registration processes.

METHODS: Contrast-enhanced CT images of 29 colorectal liver cancer patients and end-exhale four-dimensional CT images of 26 locally advanced non-small cell lung cancer patients were collected. Different combinations of parameters that determine the triangle mesh quality …

Head And Neck Radiation Therapy Patterns Of Practice Variability Identified As A Challenge To Real-World Big Data: Results From The Learning From Analysis Of Multicentre Big Data Aggregation (Lambda) Consortium, Amanda Caissie, Michelle Mierzwa, Clifton David Fuller, Murali Rajaraman, Alex Lin, Andrew Macdonald, Richard Popple, Ying Xiao, Lisanne Vandijk, Peter Balter, Helen Fong, Heping Xu, Matthew Kovoor, Joonsang Lee, Arvind Rao, Mary Martel, Reid Thompson, Brandon Merz, John Yao, Charles Mayo

Faculty, Staff and Student Publications

PURPOSE: Outside of randomized clinical trials, it is difficult to develop clinically relevant evidence-based recommendations for radiation therapy (RT) practice guidelines owing to lack of comprehensive real-world data. To address this knowledge gap, we formed the Learning from Analysis of Multicenter Big Data Aggregation consortium to cooperatively implement RT data standardization, develop software solutions for data analysis, and recommend clinical practice change based on real-world data analyzed. The first phase of this "Big Data" study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs) that would undermine subsequent use of large-scale, electronically aggregated …

Dose Escalation For Pancreas Sbrt: Potential And Limitations Of Using Daily Online Adaptive Radiation Therapy And An Iterative Isotoxicity Automated Planning Approach, Dong Joo Rhee, Sam Beddar, Joseph Abi Jaoude, Gabriel Sawakuchi, Rachael Martin, Luis Perles, Cenji Yu, Yulun He, Laurence E Court, Ethan B Ludmir, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguichi, Joshua S Niedzielski

Faculty, Staff and Student Publications

PURPOSE: To determine the dosimetric limitations of daily online adaptive pancreas stereotactic body radiation treatment by using an automated dose escalation approach.

METHODS AND MATERIALS: We collected 108 planning and daily computed tomography (CT) scans from 18 patients (18 patients × 6 CT scans) who received 5-fraction pancreas stereotactic body radiation treatment at MD Anderson Cancer Center. Dose metrics from the original non-dose-escalated clinical plan (non-DE), the dose-escalated plan created on the original planning CT (DE-ORI), and the dose-escalated plan created on daily adaptive radiation therapy CT (DE-ART) were analyzed. We developed a dose-escalation planning algorithm within the radiation treatment …

Plasma Enzymatic Activity, Proteomics And Peptidomics In Covid-19-Induced Sepsis: A Novel Approach For The Analysis Of Hemostasis, Fernando Dos Santos, Joyce B Li, Nathalia Juocys, Rafi Mazor, Laura Beretta, Nicole G Coufal, Michael T Y Lam, Mazen F Odish, Maria Claudia Irigoyen, Anthony J O'Donoghue, Federico Aletti, Erik B Kistler

Faculty, Staff and Student Publications

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained …

Oncology-Specific Radiation Dose And Image Noise Reference Levels In Adult Abdominal-Pelvic Ct, Moiz Ahmad, Xinming Liu, Ajaykumar C Morani, Dhakshinamoorthy Ganeshan, Marcus R Anderson, Ehsan Samei, Corey T Jensen

Faculty, Staff and Student Publications

OBJECTIVES: To provide our oncology-specific adult abdominal-pelvic CT reference levels for image noise and radiation dose from a high-volume, oncologic, tertiary referral center.

METHODS: The portal venous phase abdomen-pelvis acquisition was assessed for image noise and radiation dose in 13,320 contrast-enhanced CT examinations. Patient size (effective diameter) and radiation dose (CTDI

RESULTS: The noise reference level was 11.25 HU with a reference range of 10.25-12.25 HU. The dose reference level at a median effective diameter of 30.7 cm was 26.7 mGy with a reference range of 19.6-37.0 mGy. Dose increased with patient size; however, image noise remained approximately constant within …

Multidrug Resistance In The Standardized Treatment Of Colon Cancer Harboring A Rare Fibrosarcoma B-Type (Braf) Pn581i Mutation: A Case Report, Xiaoyan Wang, Chenyi Zhao, Yang Gong, Ying Wang, Feng Guo

Faculty, Staff and Student Publications

BRAF non-V600 mutations are a distinct molecular subset of colorectal cancer (CRC) that has little to no clinical similarity to the BRAF V600 mutations. It is generally considered that the BRAF non-V600 mutations correlate with better survival of CRC patients. In this report, we present an unusual case of that a midlife female patient who was initially diagnosed with stage IIIC colon cancer, and multiple metastases were found 25 months after radical surgery. Next-generation sequencing (NGS) revealed the BRAF p.N581I (c.1742A>T) mutation. She received chemotherapy, targeted therapy, and immunotherapy. However, the disease progressed rapidly with rare metastasis of the …

The Current Status And Future Prospects For Conversion Therapy In The Treatment Of Hepatocellular Carcinoma, Jinfeng Bai, Ming Huang, Bohan Song, Wei Luo, Rong Ding

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. In China, most HCC patients are diagnosed with advanced disease and in these cases surgery is challenging. Conversion therapy can be used to change unresectable HCC into resectable disease and is a potential breakthrough treatment strategy. The resection rate for unresectable advanced HCC has recently improved as a growing number of patients have benefited from conversion therapy. While conversion therapy is at an early stage of development, progress in patient selection, optimum treatment methods, and the timing of surgery have the potential to deliver significant benefits. In …

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …

Effectiveness Without Efficacy: Cautionary Tale From A Landmark Breast Cancer Randomized Controlled Trial, Yu Shen, Jing Ning, Heather Y Lin, Simona F Shaitelman, Henry M Kuerer, Isabelle Bedrosian

Faculty, Staff and Student Publications

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment …

Corrigendum: Semnet: Learning Semantic Attributes For Human Activity Recognition With Deep Belief Networks, Shanmuga Venkatachalam, Harideep Nair, Ming Zeng, Cathy Shunwen Tan, Ole J Mengshoel, John Paul Shen

Faculty, Staff and Student Publications

This corrects the article "SemNet: Learning semantic attributes for human activity recognition with deep belief networks" in volume 5, 879389.

PMID: 36968617

Clinical Parameters Affecting Survival Outcomes In Patients With Low-Grade Serous Ovarian Carcinoma: An International Multicentre Analysis, Taymaa May, Marcus Bernardini, Stephanie Lheureux, Katja K H Aben, Elisa V Bandera, Matthias W Beckmann, Javier Benitez, Andrew Berchuck, Line Bjørge, Michael E Carney, Daniel W Cramer, Anna Defazio, Thilo Dörk, Diana M Eccles, Michael Friedlander, María Jose García, Ellen L Goode, Alexander Hein, Claus K Høgdall, Allan Jensen, Sharon Johnatty, Catherine J Kennedy, Lambertus A Kiemeney, Susanne K Kjær, Jolanta Kupryjańczyk, Keitaro Matsuo, Valerie Mcguire, Francesmary Modugno, Lisa E Paddock, Tanja Pejovic, Catherine M Phelan, Marjorie J Riggan, Cristina Rodriguez-Antona, Joseph H Rothstein, Weiva Sieh, Honglin Song, Kathryn L Terry, Anne M Van Altena, Adriaan Vanderstichele, Ignace Vergote, Liv Cecilie Vestrheim Thomsen, Penelope M Webb, Nicolas Wentzensen, Lynne R Wilkens, Argyrios Ziogas, Haiyan Jiang, Alicia Tone, Ovarian Cancer Association And The Australian Ovarian Cancer Study Group

Faculty, Staff and Student Publications

BACKGROUND: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.

METHODS: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves.

RESULTS: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of …

Analysis Of Nurse And Patient Preferences For Pre-Filled Pen Devices For Self-Injection Of Highly Purified Human Menopausal Gonadotropin (Hp-Hmg, Menopurr, 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 …

Selinexor In Combination With Weekly Paclitaxel In Patients With Metastatic Solid Tumors: Results Of An Open Label, Single-Center, Multi-Arm Phase 1b Study With Expansion Phase In Ovarian Cancer, Shannon N Westin, Siqing Fu, Apostolia Tsimberidou, Sarina Piha-Paul, Fechukwu Akhmedzhanov, Bulent Yilmaz, Lacey Mcquinn, Amanda L Brink, Jing Gong, Cheuk Hong Leung, Heather Lin, David S Hong, Shubham Pant, Brett Carter, Amir Jazaeri, David Gershenson, Anil K Sood, Robert L Coleman, Jatin Shah, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

OBJECTIVE: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.

METHODS: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors. Selinexor (60 mg or 80 mg twice weekly orally) and weekly paclitaxel (80 mg IV 2 week on, 1 week off) were one of 13 parallel arms. Efficacy was evaluated using RECIST version 1.1.

RESULTS: All 35 patients …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

Faculty, Staff and Student Publications

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …