Medicine and Health Sciences Commons^™

Alpha Particle-Emitting Radiopharmaceuticals As Cancer Therapy: Biological Basis, Current Status, And Future Outlook For Therapeutics Discovery, Ryan P Coll, Scott J Bright, David K J Martinus, Dimitra K Georgiou, Gabriel O Sawakuchi, H Charles Manning

Faculty, Staff and Student Publications

Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (α) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of α-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative "theranostic" platforms. Herein, the current landscape of α particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides …

Hyperoxidized Prdx3 As A Specific Ferroptosis Marker, Yuelong Yan, Boyi Gan

Faculty, Staff and Student Publications

The lack of a reliable and specific marker for ferroptosis has hindered the advancement of treatments related to this cell death mechanism toward clinical application. A recent study published in Molecular Cell has identified hyperoxidized peroxiredoxin 3 (PRDX3) as a promising marker for ferroptosis, opening up new avenues for monitoring and targeting ferroptosis in disease treatment.

Pathomic Features Reveal Immune And Molecular Evolution From Lung Preneoplasia To Invasive Adenocarcinoma, Pingjun Chen, Frank R Rojas, Xin Hu, Alejandra Serrano, Bo Zhu, Hong Chen, Lingzhi Hong, Rukhmini Bandyoyadhyay, Muhammad Aminu, Neda Kalhor, J Jack Lee, Siba El Hussein, Joseph D Khoury, Harvey I Pass, Andre L Moreira, Vamsidhar Velcheti, Daniel H Sterman, Junya Fukuoka, Kazuhiro Tabata, Dan Su, Lisha Ying, Don L Gibbons, John V Heymach, Ignacio I Wistuba, Junya Fujimoto, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials …

Atm Mutations Associate With Distinct Co-Mutational Patterns And Therapeutic Vulnerabilities In Nsclc, Natalie I Vokes, Ana Galan Cobo, Margarita Fernandez-Chas, David Molkentine, Santiago Treviño, Vitaly Druker, Yu Qian, Sonia Patel, Stephanie Schmidt, Lingzhi Hong, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Marcelo V Negrao, Don L Gibbons, Ara Vaporciyan, Xiuning Le, Jia Wu, Jianjun Zhang, Una Rigney, Sonia Iyer, Emma Dean, John V Heymach

Faculty, Staff and Student Publications

PURPOSE: Ataxia-telangiectasia mutated (ATM) is the most frequently mutated DNA damage repair gene in non-small cell lung cancer (NSCLC). However, the molecular correlates of ATM mutations and their clinical implications have not been fully elucidated.

EXPERIMENTAL DESIGN: Clinicopathologic and genomic data from 26,587 patients with NSCLC from MD Anderson, public databases, and a de-identified nationwide (US-based) NSCLC clinicogenomic database (CGDB) were used to assess the co-mutation landscape, protein expression, and mutational processes in ATM-mutant tumors. We used the CGDB to evaluate ATM-associated outcomes in patients treated with immune checkpoint inhibitors (ICI) with or without chemotherapy, and assessed the effect of …

Clinical And Molecular Characterization Of Long-Term Survivors With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Atezolizumab Plus Carboplatin And Etoposide, Stephen V Liu, Tony S K Mok, Barzin Y Nabet, Aaron S Mansfield, Richard De Boer, György Losonczy, Shunichi Sugawara, Rafal Dziadziuszko, Maciej Krzakowski, Alexey Smolin, Maximilian J Hochmair, Marina C Garassino, Carl M Gay, John V Heymach, Lauren A Byers, Sivuonthanh Lam, Andrés Cardona, Stefanie Morris, Leah Adler, David S Shames, Martin Reck

Faculty, Staff and Student Publications

Objectives: In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.

Materials and methods: Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months …

Evaluating Strength Of Recommendations For Commonly Administered Medications In Lactating Women, Yevgenia Y Fomina, John J Byrne, Catherine Y Spong

Faculty, Staff and Student Publications

Objective: To characterize the data on medications for lactating people in the LactMed database and evaluate the strength of the data for the most commonly administered medications in lactating women.

Methods: A retrospective analysis of all medications in the LactMed database in 12/2020 was performed. Each medication was classified into one of three categories: absent data, minimal-moderate data, strong data pertaining to safety in lactation. No data was defined as no available research studies associated with the medication. Minimal-moderate data was defined as absent research studies in one or more of the four LactMed categories: maternal drug levels, infant drug …

Systematic Review And Meta-Analysis Of Immune Checkpoint Inhibitors As Single Agent Or In Combination With Chemotherapy In Early-Stage Non-Small Cell Lung Cancer: Impact Of Clinicopathological Factors And Indirect Comparison Between Treatment Strategies, Antonio Nuccio, Giuseppe Viscardi, Fabio Salomone, Alberto Servetto, Francesco Maria Venanzi, Silvia Teresa Riva, Sara Oresti, Francesca Rita Ogliari, Mariagrazia Viganò, Alessandra Bulotta, Robert Cameron, Alessandra Esposito, Jacobi Hines, Roberto Bianco, Michele Reni, Tina Cascone, Marina Chiara Garassino, Valter Torri, Giulia Veronesi, Michela Cinquini, Roberto Ferrara

Faculty, Staff and Student Publications

Background: In non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear.

Methods: Randomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS …

Competing Engagement Of Β-Arrestin Isoforms Balances Igf1r/P53 Signaling And Controls Melanoma Cell Chemotherapeutic Responsiveness, Sonia Cismas, Sylvya Pasca, Caitrin Crudden, Iara Trocoli Drakensjo, Naida Suleymanova, Simin Zhang, Benjamin Gebhard, Dawei Song, Shiyong Neo, Takashi Shibano, Terry J Smith, George A Calin, Ada Girnita, Leonard Girnita

Faculty, Staff and Student Publications

Constraints on the p53 tumor suppressor pathway have long been associated with the progression, therapeutic resistance, and poor prognosis of melanoma, the most aggressive form of skin cancer. Likewise, the insulin-like growth factor type 1 receptor (IGF1R) is recognized as an essential coordinator of transformation, proliferation, survival, and migration of melanoma cells. Given that β-arrestin (β-arr) system critically governs the anti/pro-tumorigenic p53/IGF1R signaling pathways through their common E3 ubiquitin-protein ligase MDM2, we explore whether unbalancing this system downstream of IGF1R can enhance the response of melanoma cells to chemotherapy. Altering β-arr expression demonstrated that both β-arr1-silencing and β-arr2-overexpression (-β-arr1/+β-arr2) facilitated …

Fsp1 Oxidizes Nadph To Suppress Ferroptosis, Sitao Zhang, Shengsong Gou, Qian Zhang, Xin Yong, Boyi Gan, Da Jia

Faculty, Staff and Student Publications

No abstract provided.

Heart Brain Clinic: An Integrated Approach To Stroke Care, Muhammad Bilal Tariq, Syed Kalimullah S Qadri, Anjail Sharrief, Kathleen Tulod, Abhijeet Dhoble, Sidhanta Gurung, Maria Jamilla Lacap, Munachi Okpala, Bharti Manwani, Richard W Smalling, Nicole Gonzales

Faculty, Staff and Student Publications

Background and objectives: Multidisciplinary clinics have been shown to improve care. Patients with patent foramen ovale (PFO)-associated stroke need evaluation by cardiology and neurology specialists. We report our experience creating a multidisciplinary Structural Heart Brain Clinic (HBC) with a focus on patients with PFO-associated stroke.

Methods: Demographic and clinical data were retrospectively collected for patients with PFO-associated ischemic stroke. Patients with PFO-associated stroke were divided into a standard care group and Heart Brain Clinic group for analysis. Outcome measures included time from stroke to PFO closure and number of clinic visits before decision regarding closure. Nonparametric analysis evaluated differences in …

Gru-D-Weibull: A Novel Real-Time Individualized Endpoint Prediction, Xiaoyang Ruan, Liwei Wang, Charat Thongprayoon, Wisit Cheungpasitporn, Hongfang Liu

Faculty, Staff and Student Publications

Background: In the era of healthcare digital transformation, using electronic health record (EHR) data to generate various endpoint estimates for active monitoring is highly desirable in chronic disease management. However, traditional predictive modeling strategies leveraging well-curated data sets can have limited real-world implementation potential due to various data quality issues in EHR data.

Methods: We propose a novel predictive modeling approach, GRU-D-Weibull, which models Weibull distribution leveraging gated recurrent units with decay (GRU-D), for real-time individualized endpoint prediction and population level risk management using EHR data.

Experiments: We systematically evaluated the performance and showcased the real-world implementability of the proposed …

Exploring Illness Perceptions Of Multimorbidity Among Community-Dwelling Older Adults: A Mixed Methods Study, Ayomide Okanlawon Bankole, Rozmin B Jiwani, Forgive Avorgbedor, Jing Wang, Onome H Osokpo, Sara L Gill, Carrie Jo Braden

Faculty, Staff and Student Publications

Background: Illness perceptions are individual beliefs or experiences about the nature and treatment of their illness. Although extensive research exists about illness perceptions, little is known about illness perceptions of multimorbidity.

Methods: The purpose of this parallel-convergent mixed-methods study was to comprehensively explore illness perception of multimorbidity among community dwelling older adults. Data was collected using one-on-one semi-structured interviews (n=17) and the Multimorbidity Illness Perception Scale (MULTIPleS) (n=116). Qualitative data were analyzed using content analysis while quantitative data were analyzed with descriptive and inferential statistics. Both qualitative and quantitative findings were integrated to identify differences in illness perceptions of multimorbidity …

Acute Myeloid Leukemia With Mutated Tp53: Is This Newly Proposed Entity Oversimplifying A Complex Group Of Neoplasms?, Hong Fang, L Jeffery Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Psychological Distress And Mental Health Care Utilization Among Hispanic/Latino Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Christabel K Cheung, Andrea C Betts, John M Salsman, Clark R Andersen, Carol Yesenia Ochoa-Dominguez, Kimberly Miller, Joel Milam, Ashna Shah, Susan K Peterson, Qian Lu, J Andrew Livingston, Michelle A T Hildebrandt, Susan K Parsons, David Freyer, Michael E Roth

Faculty, Staff and Student Publications

Purpose: Survivors of adolescent and young adult (AYA) cancer experience psychological distress and insufficient access to mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes in this population. This study compared psychological distress, mental health care use, and inability to afford mental health care between Hispanic/Latino survivors of AYA cancer and Hispanic/Latino controls.

Methods: The National Health Interview Survey data (2010-2018) were analyzed to identify Hispanic/Latino survivors of AYA cancer and Hispanic/Latino age- and sex-matched non-cancer controls. Sociodemographic, chronic health, modifiable factors, and psychological outcomes were compared using chi-square tests. Logistic regression models with survey weights …

Development And Validation Of Age-Specific Risk Prediction Models For Primary Ovarian Insufficiency In Long-Term Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study And St Jude Lifetime Cohort, Cindy Im, Zhe Lu, Sogol Mostoufi-Moab, Angela Delaney, Lin Yu, Jessica L Baedke, Yutong Han, Yadav Sapkota, Yutaka Yasui, Eric J Chow, Rebecca M Howell, Smita Bhatia, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Paul C Nathan, Yan Yuan

Faculty, Staff and Student Publications

BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer.

METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We …

Poor Sit-To-Stand Performance In Adolescent And Young Adult Patients With Sarcoma, Savannah V Wooten, Behrang Amini, J Andrew Livingston, Michelle A T Hildebrandt, Joya Chandra, Susan C Gilchrist, Michael Roth, Eugenie Kleinerman

Faculty, Staff and Student Publications

Background: Adolescents and young adult (AYA) patients with sarcoma are at heightened risk of reduced physical capacity and disease-related weakness. Sit-to-stand (STS) performance correlates with lower extremity functionality and activities of daily living; however, little is known regarding the relationship between muscular status and STS performance in patients with sarcoma. This study assessed STS performance in patients with sarcoma and the association between STS performance and the skeletal muscle index (SMI) and skeletal muscle density (SMD).

Methods: This study included 30 patients with sarcoma (15-39 years old) treated with high-dose doxorubicin. Patients performed the five-times-STS test before starting treatment and …

Enhanced Cd19 Activity In B Cells Contributes To Immunodeficiency In Mice Deficient In The Icf Syndrome Gene Zbtb24, Zhengzhou Ying, Swanand Hardikar, Joshua B Plummer, Tewfik Hamidi, Bin Liu, Yueping Chen, Jianjun Shen, Yunxiang Mu, Kevin M Mcbride, Taiping Chen

Faculty, Staff and Student Publications

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. It is caused by mutations in DNMT3B, ZBTB24, CDCA7, or HELLS. While progress has been made in elucidating the roles of these genes in regulating DNA methylation, little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype. Here, we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF syndrome. Specifically, Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels …

A Retrospective Examination Of Pain In Acute Stroke At Hospital Discharge, Deniz Dishman, Tia Lal, Christin Silos, Luyao Chen, Xiaoqian Jiang, Jennifer Beauchamp, Seema Aggarwal, Charles Green, Sean I Savitz

Faculty, Staff and Student Publications

Objectives: Pain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors' function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls.

Materials and methods: Using discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted …

Sam: Self-Adapting Mixture Prior To Dynamically Borrow Information From Historical Data In Clinical Trials, Peng Yang, Yuansong Zhao, Lei Nie, Jonathon Vallejo, Ying Yuan

Faculty, Staff and Student Publications

Mixture priors provide an intuitive way to incorporate historical data while accounting for potential prior-data conflict by combining an informative prior with a noninformative prior. However, prespecifying the mixing weight for each component remains a crucial challenge. Ideally, the mixing weight should reflect the degree of prior-data conflict, which is often unknown beforehand, posing a significant obstacle to the application and acceptance of mixture priors. To address this challenge, we introduce self-adapting mixture (SAM) priors that determine the mixing weight using likelihood ratio test statistics or Bayes factors. SAM priors are data-driven and self-adapting, favoring the informative (noninformative) prior component …

Outcomes Of Autologous Stem Cell Transplantation In Patients With Ultra-High-Risk Multiple Myeloma, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Adeel Masood, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM). This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT). We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by …

Repeated Encounters For Actinic Keratoses In Medicare Patients: A Retrospective Cohort Study, Nasim Khalfe, Lucy J Navsaria, Yao Li, Malgorzata K Nowakowska, Carly F Stender, Candice L Hinkston, Sharon H Giordano, Sanjay S Shete, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Innovations, Advances, And Challenges In Precision Radiation Oncology Physics, Fada Guan, Lawrence Bronk, Jinbo Yue, Radhe Mohan, Zhe Chen

Faculty, Staff and Student Publications

No abstract provided.

Improving Radiotherapy In Immunosuppressive Microenvironments By Targeting Complement Receptor C5ar1, Callum Beach, David Maclean, Dominika Majorova, Stavros Melemenidis, Dhanya K Nambiar, Ryan K Kim, Gabriel N Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily Vs Hillson, Ashley K Mcculloch, Ross K Mcmahon, Kathryn Pennel, Joanne Edwards, Sean M O'Cathail, Campbell S Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C Koong, Trent M Woodruff, Edward E Graves, Tim Maughan, Simon Ja Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J Leedham, Amato J Giaccia, Monica M Olcina

Faculty, Staff and Student Publications

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased …

An Opioid-Minimizing Multimodal Pain Regimen Reduces Opioid Exposure And Pain In Trauma-Injured Patients At High Risk For Opioid Misuse: Secondary Analysis From The Mast Trial, Constanza De Dios, Robert Suchting, Charles Green, James M Klugh, John A Harvin, Heather E Webber, Joy M Schmitz, Scott D Lane, Jin H Yoon, Angela Heads, Kandice Motley, Angela Stotts

Faculty, Staff and Student Publications

BACKGROUND: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse.

METHODS: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original …

Influenza Viral Infection Is A Risk Factor For Severe Illness In Covid-19 Patients: A Nationwide Population-Based Cohort Study, Jeong-Hwan Hwang, Yeon Seok You, Sang Woo Yeom, Min Gyu Lee, Jong-Hwan Lee, Min Gul Kim, Jong Seung Kim

Faculty, Staff and Student Publications

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with …

Effect Of Epithelial-Specific Myd88 Signaling Pathway On Airway Inflammatory Response To Organic Dust Exposure, Amber N Johnson, John Dickinson, Amy Nelson, Rohit Gaurav, Katrina Kudrna, Scott E Evans, Katherine Janike, Todd A Wyatt, Jill A Poole

Faculty, Staff and Student Publications

The Toll-like receptor (TLR) adaptor protein MyD88 is integral to airway inflammatory response to microbial-enriched organic dust extract (ODE) exposures. ODE-induced airway neutrophil influx and release of pro-inflammatory cytokines was essentially abrogated in global MyD88-deficient mice, yet these mice demonstrate an increase in airway epithelial cell mucin expression. To further elucidate the role of MyD88-dependent responses specific to lung airway epithelial cells in response to ODE in vivo, the surfactant protein C protein (SPC) Cre+ embryologic expressing airway epithelial cells floxed for MyD88 to disrupt MyD88 signaling were utilized. The inducible club cell secretory protein (CCSP) Cre+, MyD88 floxed, …

Influence Of Treatment Intensity And Medical Comorbidities In Older Adults With Peripheral T Cell Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V Danilov, Swaminathan Iyer, Sharon H Giordano

Faculty, Staff and Student Publications

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N …

Inhibition Of The Proline Metabolism Rate-Limiting Enzyme P5cs Allows Proliferation Of Glutamine-Restricted Cancer Cells, Samantha J Linder, Tiziano Bernasocchi, Bárbara Martínez-Pastor, Kelly D Sullivan, Matthew D Galbraith, Caroline A Lewis, Christina M Ferrer, Ruben Boon, Giorgia G Silveira, Hyo Min Cho, Charles Vidoudez, Stuti Shroff, Joao P Oliveira-Costa, Kenneth N Ross, Rami Massri, Yusuke Matoba, Eugene Kim, Bo R Rueda, Shannon L Stott, Eyal Gottlieb, Joaquin M Espinosa, Raul Mostoslavsky

Faculty, Staff and Student Publications

Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood. Here, using an unbiased screen, we identify ALDH18A1, which encodes P5CS, the rate-limiting enzyme in the proline biosynthetic pathway, as a gene that cells can downregulate in response to glutamine starvation. Notably, P5CS downregulation promotes de novo glutamine synthesis, highlighting a previously unrecognized …

The Impact Of Covid-19 On Managing Ophthalmic Diseases: An International, Descriptive Study, Ethan Waisberg, Joshua Ong, Nasif Zaman, Sharif Amit Kamran, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Background: Anecdotally, the COVID-19 pandemic has resulted in more severe cases of eye disease, decreased medication compliance/availability, and decreased treatment volume due to the lockdown.

Aims: We aim to quantify and bring together a variety of international perspectives from ophthalmologists of different subspecialties to characterize the global impact of COVID-19 on managing various ophthalmic disease.

Methods: An online survey of 10 questions was conducted among ophthalmologists using a specialized survey program.

Results: Fifty-two ophthalmologists were successfully contacted. Survey respondents include ophthalmologists from USA, Canada, Korea, Mexico, and New Zealand. Based on the results of our survey, 1 year after the …

Clinico-Genomic Profiling Of Conventional And Dedifferentiated Chondrosarcomas Reveals Tp53 Mutation To Be Associated With Worse Outcomes, Ryan A Denu, Richard K Yang, Alexander J Lazar, Shalin S Patel, Valerae O Lewis, Jason Roszik, J Andrew Livingston, Wei-Lien Wang, Kenna R Shaw, Ravin Ratan, Maria A Zarzour, Justin Bird, Shaan Raza, Kadir C Akdemir, Jordi Rodon Ahnert, Vivek Subbiah, Shreyaskumar Patel, Anthony P Conley

Faculty, Staff and Student Publications

PURPOSE: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.

EXPERIMENTAL DESIGN: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas.

RESULTS: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising …