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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 Jan 2023

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 …


Text Classification Of Cancer Clinical Trial Eligibility Criteria, Yumeng Yang, Soumya Jayaraj, Ethan Ludmir, Kirk Roberts Jan 2023

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 Jan 2023

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 …


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 Jan 2023

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 …


Transiently Impaired Endothelial Function During Thyroid Hormone Withdrawal In Differentiated Thyroid Cancer Patients, Li-Ying Hou, Xiao Li, Guo-Qiang Zhang, Chuang Xi, Chen-Tian Shen, Hong-Jun Song, Wen-Kun Bai, Zhong-Ling Qiu, Quan-Yong Luo Jan 2023

Transiently Impaired Endothelial Function During Thyroid Hormone Withdrawal In Differentiated Thyroid Cancer Patients, Li-Ying Hou, Xiao Li, Guo-Qiang Zhang, Chuang Xi, Chen-Tian Shen, Hong-Jun Song, Wen-Kun Bai, Zhong-Ling Qiu, Quan-Yong Luo

Faculty, Staff and Student Publications

PURPOSE: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.

METHODS: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the …


Revisiting The Type Species Of The Genus Homidia (Collembola, Entomobryidae), Guo-Qiang Zhang, Yu-Xin Zhao, Feng Zhang Jan 2023

Revisiting The Type Species Of The Genus Homidia (Collembola, Entomobryidae), Guo-Qiang Zhang, Yu-Xin Zhao, Feng Zhang

Faculty, Staff and Student Publications

Homidiacingula Börner, 1906, the type species of the genus Homidia Börner, 1906, is widespread from India to Southeast Asia, but its detailed morphological characteristics have not yet been described. We examined the morphology of specimens of H.cingula from Indonesia and southwestern China and confirmed their conspecific status by comparing their DNA barcoding sequences. We also compared the morphology of H.cingula with other two closely related species, confirming the valid species status of H.subcingula Denis, 1948. Our study provides new taxonomic and molecular data for the genus Homidia.


Selection And Validation Of Optimal Reference Genes For Rt-Qpcr Analyses In Aphidoletes Aphidimyza Rondani (Diptera: Cecidomyiidae), Xiu-Xian Shen, Guo-Qiang Zhang, Yu-Xin Zhao, Xiao-Xiao Zhu, Xiao-Fei Yu, Mao-Fa Yang, Feng Zhang Jan 2023

Selection And Validation Of Optimal Reference Genes For Rt-Qpcr Analyses In Aphidoletes Aphidimyza Rondani (Diptera: Cecidomyiidae), Xiu-Xian Shen, Guo-Qiang Zhang, Yu-Xin Zhao, Xiao-Xiao Zhu, Xiao-Fei Yu, Mao-Fa Yang, Feng Zhang

Faculty, Staff and Student Publications

Aphidoletes aphidimyza is a predator that is an important biological agent used to control agricultural and forestry aphids. Although many studies have investigated its biological and ecological characteristics, few molecular studies have been reported. The current study was performed to identify suitable reference genes to facilitate future gene expression and function analyses via quantitative reverse transcription PCR. Eight reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RPS13, RPL8, RPS3, α-Tub, β-actin, RPL32, and elongation factor 1 alpha (EF1-α) were selected. Their expression levels were determined under four different experimental conditions (developmental stages, adult …


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 Jan 2023

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 …


Anti-Inflammatory Effects Of Vagus Nerve Stimulation In Pediatric Patients With Epilepsy, Supender Kaur, Nathan R Selden, Alejandro Aballay Jan 2023

Anti-Inflammatory Effects Of Vagus Nerve Stimulation In Pediatric Patients With Epilepsy, Supender Kaur, Nathan R Selden, Alejandro Aballay

Faculty, Staff and Student Publications

INTRODUCTION: The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.

METHODS: Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression …


Gene Expression In Mice With Endothelium-Specific Telomerase Knockout, Zhanguo Gao, Yongmei Yu, Yulin Dai, Zhongming Zhao, Kristin Eckel-Mahan, Mikhail G Kolonin Jan 2023

Gene Expression In Mice With Endothelium-Specific Telomerase Knockout, Zhanguo Gao, Yongmei Yu, Yulin Dai, Zhongming Zhao, Kristin Eckel-Mahan, Mikhail G Kolonin

Faculty, Staff and Student Publications

No abstract provided.


Pediatric Traumatic Brain Injury In The Middle East And North Africa Region: A Systematic Review And Meta-Analysis To Assess Characteristics, Mechanisms, And Risk Factors, Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy Jan 2023

Pediatric Traumatic Brain Injury In The Middle East And North Africa Region: A Systematic Review And Meta-Analysis To Assess Characteristics, Mechanisms, And Risk Factors, Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy

Faculty, Staff and Student Publications

Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of …


Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le Jan 2023

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …


Digital Solutions Observed In Clinical Trials: A Formative Feasibility Scoping Review, Taylor M Harrison, Sungrim Moon, Liwei Wang, Sunyang Fu, Hongfang Liu Jan 2023

Digital Solutions Observed In Clinical Trials: A Formative Feasibility Scoping Review, Taylor M Harrison, Sungrim Moon, Liwei Wang, Sunyang Fu, Hongfang Liu

Faculty, Staff and Student Publications

Growing digital access accelerates digital transformation of clinical trials where digital solutions (DSs) are increasingly and widely leveraged for improving trial efficiency, effectiveness, and accessibility. Many factors impact DS success including technology barriers, privacy concerns, or user engagement activities. It is unclear how those factors are considered or reported in the literature. Here, we perform a formative feasibility scoping review to identify gaps impacting DS quality and reproducibility in trials. Articles containing digital terms published in English from 2009 to 2022 were collected (n=4,167). 130 articles published between 2016 and 2022 were randomly selected for full-text review. Eligible articles (n=100) …


Contextual Variation Of Clinical Notes Induced By Ehr Migration, Kurt Miller, Sungrim Moon, Sunyang Fu, Hongfang Liu Jan 2023

Contextual Variation Of Clinical Notes Induced By Ehr Migration, Kurt Miller, Sungrim Moon, Sunyang Fu, Hongfang Liu

Faculty, Staff and Student Publications

The structure and semantics of clinical notes vary considerably across different Electronic Health Record (EHR) systems, sites, and institutions. Such heterogeneity hampers the portability of natural language processing (NLP) models in extracting information from the text for clinical research or practice. In this study, we evaluate the contextual variation of clinical notes by measuring the semantic and syntactic similarity of the notes of two sets of physicians comprising four medical specialties across EHR migrations at two Mayo Clinic sites. We find significant semantic and syntactic variation imposed by the context of the EHR system and between medical specialties whereas only …


Keystroke-Dynamics For Parkinson's Disease Signs Detection In An At-Home Uncontrolled Population: A New Benchmark And Method, Shikha Tripathi, Teresa Arroyo-Gallego, Luca Giancardo Jan 2023

Keystroke-Dynamics For Parkinson's Disease Signs Detection In An At-Home Uncontrolled Population: A New Benchmark And Method, Shikha Tripathi, Teresa Arroyo-Gallego, Luca Giancardo

Faculty, Staff and Student Publications

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease disorder in the world. A prompt diagnosis would enable clinical trials for disease-modifying neuroprotective therapies. Recent research efforts have unveiled imaging and blood markers that have the potential to be used to identify PD patients promptly, however, the idiopathic nature of PD makes these tests very hard to scale to the general population. To this end, we need an easily deployable tool that would enable screening for PD signs in the general population. In this work, we propose a new set of features based on keystroke dynamics, i.e., the time …


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 Jan 2023

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 …


The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai Jan 2023

The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai

Faculty, Staff and Student Publications

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse …


Emulate Randomized Clinical Trials Using Heterogeneous Treatment Effect Estimation For Personalized Treatments: Methodology Review And Benchmark, Yaobin Ling, Pulakesh Upadhyaya, Luyao Chen, Xiaoqian Jiang, Yejin Kim Jan 2023

Emulate Randomized Clinical Trials Using Heterogeneous Treatment Effect Estimation For Personalized Treatments: Methodology Review And Benchmark, Yaobin Ling, Pulakesh Upadhyaya, Luyao Chen, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Big data and (deep) machine learning have been ambitious tools in digital medicine, but these tools focus mainly on association. Intervention in medicine is about the causal effects. The average treatment effect has long been studied as a measure of causal effect, assuming that all populations have the same effect size. However, no "one-size-fits-all" treatment seems to work in some complex diseases. Treatment effects may vary by patient. Estimating heterogeneous treatment effects (HTE) may have a high impact on developing personalized treatment. Lots of advanced machine learning models for estimating HTE have emerged in recent years, but there has been …


Survey Of West Nile And Banzi Viruses In Mosquitoes, South Africa, 2011-2018, Caitlin Macintyre, Milehna Mara Guarido, Megan Amy Riddin, Todd Johnson, Leo Braack, Maarten Schrama, Erin Gorsich, Antonio Paulo Gouveia Almeida, Marietjie Venter Jan 2023

Survey Of West Nile And Banzi Viruses In Mosquitoes, South Africa, 2011-2018, Caitlin Macintyre, Milehna Mara Guarido, Megan Amy Riddin, Todd Johnson, Leo Braack, Maarten Schrama, Erin Gorsich, Antonio Paulo Gouveia Almeida, Marietjie Venter

Faculty, Staff and Student Publications

We collected >40,000 mosquitoes from 5 provinces in South Africa during 2011-2018 and screened for zoonotic flaviviruses. We detected West Nile virus in mosquitoes from conservation and periurban sites and potential new mosquito vectors; Banzi virus was rare. Our results suggest flavivirus transmission risks are increasing in South Africa.


Advances In The Management Of Spinal Metastases: What The Radiologist Needs To Know, Sarah M Bahouth, Debra N Yeboa, Amol J Ghia, Claudio E Tatsui, Christopher A Alvarez-Breckenridge, Thomas H Beckham, Andrew J Bishop, Jing Li, Mary Frances Mcaleer, Robert Y North, Laurence D Rhines, Todd A Swanson, Wang Chenyang, Behrang Amini Jan 2023

Advances In The Management Of Spinal Metastases: What The Radiologist Needs To Know, Sarah M Bahouth, Debra N Yeboa, Amol J Ghia, Claudio E Tatsui, Christopher A Alvarez-Breckenridge, Thomas H Beckham, Andrew J Bishop, Jing Li, Mary Frances Mcaleer, Robert Y North, Laurence D Rhines, Todd A Swanson, Wang Chenyang, Behrang Amini

Faculty, Staff and Student Publications

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute.


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 Jan 2023

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 …


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 Jan 2023

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 …


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 Jan 2023

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 Jan 2023

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 …


Disruption Of Fos Causes Craniofacial Anomalies In Developing Zebrafish, Lorena Maili, Bhavna Tandon, Qiuping Yuan, Simone Menezes, Frankie Chiu, S Shahrukh Hashmi, Ariadne Letra, George T Eisenhoffer, Jacqueline T Hecht Jan 2023

Disruption Of Fos Causes Craniofacial Anomalies In Developing Zebrafish, Lorena Maili, Bhavna Tandon, Qiuping Yuan, Simone Menezes, Frankie Chiu, S Shahrukh Hashmi, Ariadne Letra, George T Eisenhoffer, Jacqueline T Hecht

Faculty, Staff and Student Publications

Craniofacial development is a complex and tightly regulated process and disruptions can lead to structural birth defects, the most common being nonsyndromic cleft lip and palate (NSCLP). Previously, we identified FOS as a candidate regulator of NSCLP through family-based association studies, yet its specific contributions to oral and palatal formation are poorly understood. This study investigated the role of fos during zebrafish craniofacial development through genetic disruption and knockdown approaches. Fos was expressed in the periderm, olfactory epithelium and other cell populations in the head. Genetic perturbation of fos produced an abnormal craniofacial phenotype with a hypoplastic oral cavity that …


Spatial Modelling Of The Tumor Microenvironment From Multiplex Immunofluorescence Images: Methods And Applications, Gayatri Kumar, Renganayaki Krishna Pandurengan, Edwin Roger Parra, Kasthuri Kannan, Cara Haymaker Jan 2023

Spatial Modelling Of The Tumor Microenvironment From Multiplex Immunofluorescence Images: Methods And Applications, Gayatri Kumar, Renganayaki Krishna Pandurengan, Edwin Roger Parra, Kasthuri Kannan, Cara Haymaker

Faculty, Staff and Student Publications

Spatial modelling methods have gained prominence with developments in high throughput imaging platforms. Multiplex immunofluorescence (mIF) provides the scope to examine interactions between tumor and immune compartment at single cell resolution using a panel of antibodies that can be chosen based on the cancer type or the clinical interest of the study. The markers can be used to identify the phenotypes and to examine cellular interactions at global and local scales. Several translational studies rely on key understanding of the tumor microenvironment (TME) to identify drivers of immune response in immunotherapy based clinical trials. To improve the success of ongoing …


Trem-1, Trem-2 And Their Association With Disease Severity In Patients With Covid-19, Ruyue Fan, Zuowang Cheng, Zhisheng Huang, Ying Yang, Na Sun, Bin Hu, Peibin Hou, Bo Liu, Chuanjun Huang, Shuai Liu Jan 2023

Trem-1, Trem-2 And Their Association With Disease Severity In Patients With Covid-19, Ruyue Fan, Zuowang Cheng, Zhisheng Huang, Ying Yang, Na Sun, Bin Hu, Peibin Hou, Bo Liu, Chuanjun Huang, Shuai Liu

Faculty, Staff and Student Publications

BACKGROUND: Delayed diagnosis and inadequate treatment caused by limited biomarkers are associated with the outcomes of COVID-19 patients. It is necessary to identify other promising biomarkers and candidate targets for defining dysregulated inflammatory states.

METHODS: The triggering receptors expressed on myeloid cell (TREM)-1 and TREM-2 expression from hospitalized COVID-19 patients were characterized using ELISA and flow cytometry, respectively. Their correlation with disease severity and contrast with the main clinical indicators were evaluated.

RESULTS: Increased expression of soluble TREM-1 and TREM-2 in the plasma of COVID-19 patients was found compared to the control group. Moreover, membrane-bound TREM-1 and TREM-2 expression was …


Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter Jan 2023

Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter

Faculty, Staff and Student Publications

RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular …


Gibbs Process Distinguishes Survival And Reveals Contact-Inhibition Genes In Glioblastoma Multiforme, Afrooz Jahedi, Gayatri Kumar, Lavanya Kannan, Tarjani Agarwal, Jason Huse, Krishna Bhat, Kasthuri Kannan Jan 2023

Gibbs Process Distinguishes Survival And Reveals Contact-Inhibition Genes In Glioblastoma Multiforme, Afrooz Jahedi, Gayatri Kumar, Lavanya Kannan, Tarjani Agarwal, Jason Huse, Krishna Bhat, Kasthuri Kannan

Faculty, Staff and Student Publications

Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor …


Longitudinal Dynamic Contrast-Enhanced Mri Radiomic Models For Early Prediction Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Bikash Panthi, Rania M Mohamed, Beatriz E Adrada, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Deanna L Lane, Huong C Le-Petross, Jessica W T Leung, Jennifer K Litton, Sanaz Pashapoor, Frances Perez, Jong Bum Son, Jia Sun, Alastair Thompson, Debu Tripathy, Vicente Valero, Peng Wei, Jason White, Zhan Xu, Wei Yang, Zijian Zhou, Clinton Yam, Gaiane M Rauch, Jingfei Ma Jan 2023

Longitudinal Dynamic Contrast-Enhanced Mri Radiomic Models For Early Prediction Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Bikash Panthi, Rania M Mohamed, Beatriz E Adrada, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Deanna L Lane, Huong C Le-Petross, Jessica W T Leung, Jennifer K Litton, Sanaz Pashapoor, Frances Perez, Jong Bum Son, Jia Sun, Alastair Thompson, Debu Tripathy, Vicente Valero, Peng Wei, Jason White, Zhan Xu, Wei Yang, Zijian Zhou, Clinton Yam, Gaiane M Rauch, Jingfei Ma

Faculty, Staff and Student Publications

Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions …