Medical Specialties Commons^™

The Boring Schwann Cells: Tumor Me-Tast-Asis Along Nerves, Moran Amit, Anirban Maitra

Faculty, Staff and Student Publications

Perineural spread is an ominous feature of cancer. Here, Deborde and colleagues describe for the first time the biophysical coupling driving this route of tumor spread and the role of Schwann cell activation in the mobilization of cancer cells within and along the tumor-associated nerves. See related article by Deborde et al., p. 2454 (8).

Single-Cell Transcriptomic Profiling Reveals The Tumor Heterogeneity Of Small-Cell Lung Cancer, Yanhua Tian, Qingqing Li, Zhenlin Yang, Shu Zhang, Jiachen Xu, Zhijie Wang, Hua Bai, Jianchun Duan, Bo Zheng, Wen Li, Yueli Cui, Xin Wang, Rui Wan, Kailun Fei, Jia Zhong, Shugeng Gao, Jie He, Carl M Gay, Jianjun Zhang, Jie Wang, Fuchou Tang

Faculty, Staff and Student Publications

Small-cell lung cancer (SCLC) is the most aggressive and lethal subtype of lung cancer, for which, better understandings of its biology are urgently needed. Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment (TME) and investigate their roles in tumorigenic processes. Here, we performed high-precision single-cell transcriptomic analysis of ~5000 individual cells from primary tumors (PTs) and matched normal adjacent tissues (NATs) from 11 SCLC patients, including one patient with both PT and relapsed tumor (RT). The comparison revealed an immunosuppressive landscape of human SCLC. Malignant cells in SCLC tumors exhibited diverse states mainly related …

Distinct Immune Signature Predicts Progression Of Vestibular Schwannoma And Unveils A Possible Viral Etiology, Moran Amit, Tongxin Xie, Frederico O Gleber-Netto, Patrick J Hunt, Gautam U Mehta, Diana Bell, Deborah A Silverman, Ismail Yaman, Yi Ye, Jared K Burks, Gregory N Fuller, Paul W Gidley, Marc-Elie Nader, Shaan M Raza, Franco Demonte

Faculty, Staff and Student Publications

BACKGROUND: The management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease's variable progression rate. We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression.

METHODS: We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or …

Biophysics Of Cancer, Alemayehu A Gorfe

Faculty, Staff and Student Publications

No abstract provided.

Association Between Mnsod Activity And Cognitive Impairment In Unmedicated First-Episode Schizophrenia: Regulated By Mnsod Ala-9val Gene Polymorphism, Dong Mei Wang, Rong Rong Zhu, Yang Tian, Kadir Uludag, Jia Jing Chen, Hui Xia Zhou, Li Wang, Thomas R Kosten, Xiang Yang Zhang

Faculty, Staff and Students Publications

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment …

Association Of Prediagnosis Obesity And Postdiagnosis Aspirin With Survival From Stage Iv Colorectal Cancer, Jennifer S Davis, Janelle C Chavez, Melissa Kok, Yazmin San Miguel, Hwa Young Lee, Henry Henderson, Michael J Overman, Van Morris, Bryan Kee, David Fogelman, Shailesh M Advani, Benny Johnson, Christine Parseghian, John Paul Shen, Arvind Dasari, Kenna R Shaw, Eduardo Vilar, Kanwal P Raghav, Imad Shureiqi, Robert A Wolff, Funda Meric-Bernstam, Dipen Maru, David G Menter, Scott Kopetz, Shine Chang

Faculty, Staff and Student Publications

IMPORTANCE: The potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear.

OBJECTIVE: To evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used self-reported data from patients with metastatic or treatment-refractory disease who consented to a clinical protocol at MD Anderson Cancer Center, a large US cancer treatment …

Racial And Ethnic Differences In The Association Of Low-Carbohydrate Diet With Mortality In The Multi-Ethnic Study Of Atherosclerosis, Seung-Won Oh, Alexis C Wood, Seung-Sik Hwang, Matthew Allison

Children’s Nutrition Research Center Staff Publications

Importance: Evidence linking low-carbohydrate diets (LCDs) to mortality is limited among multiethnic populations.

Objective: To evaluate the association between LCDs and mortality by race and ethnicity.

Design, setting, and participants: The Multi-Ethnic Study of Atherosclerosis is a large, population-based prospective cohort study of adults aged 45 to 84 years recruited from 6 US communities. A total of 6109 participants without baseline cardiovascular disease were included in this analysis. Baseline data were collected from July 2000 to August 2002, with follow-up completed by December 2017. The data were analyzed between May 2021 and April 2022.

Exposures: Food frequency questionnaires were used …

Egfr Suppresses P53 Function By Promoting P53 Binding To Dna-Pkcs: A Noncanonical Regulatory Axis Between Egfr And Wild-Type P53 In Glioblastoma, Jie Ding, Xiaolong Li, Sabbir Khan, Chen Zhang, Feng Gao, Shayak Sen, Amanda R Wasylishen, Yang Zhao, Guillermina Lozano, Dimpy Koul, W K Alfred Yung

Faculty, Staff and Student Publications

Background: Epidermal growth factor receptor (EGFR) amplification and TP53 mutation are the two most common genetic alterations in glioblastoma multiforme (GBM). A comprehensive analysis of the TCGA GBM database revealed a subgroup with near mutual exclusivity of EGFR amplification and TP53 mutations indicative of a role of EGFR in regulating wild-type-p53 (wt-p53) function. The relationship between EGFR amplification and wt-p53 function remains undefined and this study describes the biological significance of this interaction in GBM.

Methods: Mass spectrometry was used to identify EGFR-dependent p53-interacting proteins. The p53 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) interaction was detected by co-immunoprecipitation. We …

Family Planning, Fertility, And Career Decisions Among Female Oncologists, Anna Lee, Aleksandra Kuczmarska-Haas, Shraddha M Dalwadi, Erin F Gillespie, Michelle S Ludwig, Emma B Holliday, Fumiko Chino

Faculty, Staff and Student Publications

Importance: Female oncologists often spend their childbearing years in training and establishing careers, with many later experiencing fertility issues when starting a family. Physician fertility and family planning are rarely discussed during training. Attitudes among female oncologists regarding family planning are unknown.

Objectives: To understand barriers to family planning as well as the association of fertility treatment with career decisions and to assess experiences of pregnancy-based discrimination among female oncologists.

Design, setting, and participants: In this survey study, a novel 39-item questionnaire was distributed to US female oncologists from May 7 to June 30, 2020, via email and social media …

Brain Metastases: A Society For Neuro-Oncology (Sno) Consensus Review On Current Management And Future Directions, Ayal A Aizer, Nayan Lamba, Manmeet S Ahluwalia, Kenneth Aldape, Adrienne Boire, Priscilla K Brastianos, Paul D Brown, D Ross Camidge, Veronica L Chiang, Michael A Davies, Leland S Hu, Raymond Y Huang, Timothy Kaufmann, Priya Kumthekar, Keng Lam, Eudocia Q Lee, Nancy U Lin, Minesh Mehta, Michael Parsons, David A Reardon, Jason Sheehan, Riccardo Soffietti, Hussein Tawbi, Michael Weller, Patrick Y Wen

Faculty, Staff and Student Publications

Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, …

Classification Of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics, Katelyn F Handley, Travis T Sims, Nicholas W Bateman, Deanna Glassman, Katherine I Foster, Sanghoon Lee, Jun Yao, Hui Yao, Bryan M Fellman, Jinsong Liu, Zhen Lu, Kelly A Conrads, Brian L Hood, Waleed Barakat, Li Zhao, Jianhua Zhang, Shannon N Westin, Joseph Celestino, Kelly M Rangel, Sunil Badal, Igor Pereira, Prahlad T Ram, George L Maxwell, Livia S Eberlin, P Andrew Futreal, Robert C Bast, Nicole D Fleming, Thomas P Conrads, Anil K Sood

Faculty, Staff and Student Publications

IMPORTANCE: Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics.

OBJECTIVE: To develop and characterize a gross morphologic classification system for HGSOC.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with suspected advanced-stage ovarian cancer who presented between April 1, 2013, and August 5, 2016, to the University of Texas MD Anderson Cancer Center, a large referral center. Patients underwent laparoscopic assessment of disease burden before treatment and received a histopathologic diagnosis of …

Impact Of Treatment Modality On Pelvic Floor Dysfunction Among Uterine Cancer Survivors, David S Lakomy, Alison K Yoder, Juliana Wu, Mike Hernandez, Martins Ayoola-Adeola, Anuja Jhingran, Ann Klopp, Pamela Soliman, Susan K Peterson, Lilie L Lin

Faculty, Staff and Student Publications

Objective: Pelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications.

Methods: We used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact …

Inequity In National Institutes Of Health Predoctoral Fellowships, 2001-2020, Mytien Nguyen, Nghia D Nguyen, Sarwat I Chaudhry, Mayur M Desai, Jose E Cavazos, Dowin Boatright

Faculty, Staff and Student Publications

This cross-sectional study examines trends in number of awards and funding of general and diversity F31 predoctoral fellowships from 2001 to 2020.

Endoscopic Ultrasound-Guided Radiofrequency Ablation (Eus-Rfa) For Advanced Pancreatic And Periampullary Adenocarcinoma, Nirav Thosani, Putao Cen, Julie Rowe, Sushovan Guha, Jennifer M Bailey-Lundberg, Dimpal Bhakta, Prithvi Patil, Curtis J Wray

Faculty, Staff and Student Publications

Long term prognosis and 5-year survival for pancreatic adenocarcinoma (PDAC) remains suboptimal. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding safety and long-term outcomes. The aim of this study is to report safety-profile, feasibility and outcomes of EUS-RFA for advanced PDAC. Prospective review of patients with diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long-term follow up (> 30 months). Study patients underwent a total of 1-4 RFA sessions. All patients were enrolled in longitudinal cohort study and received standard of care chemotherapy. 10 patients underwent …

Association Of Early Steroid Administration With Outcomes Of Children Hospitalized For Covid-19 Without Multisystem Inflammatory Syndrome In Children, Sandeep Tripathi, Meghana Nadiger, Jeremy S Mcgarvey, Aaron A Harthan, Monica Lombardo, Varsha P Gharpure, Nicholas Perkins, Kathleen Chiotos, Imran A Sayed, Erica C Bjornstad, Utpal S Bhalala, Umamaheswara Raju, Aaron S Miller, Heda Dapul, Vicki Montgomery, Karen Boman, Grace M Arteaga, Vikas Bansal, Neha Deo, Aysun Tekin, Ognjen Gajic, Vishakha K Kumar, Rahul Kashyap, Allan J Walkey

Faculty, Staff and Students Publications

IMPORTANCE: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).

OBJECTIVE: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data retrospectively for children (<18 >years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate …

Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Kamran Hessami, Amir Hossein Norooznezhad, Sonia Monteiro, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

IMPORTANCE: Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

OBJECTIVES: To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

DATA SOURCES: PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

STUDY SELECTION: Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic …

Association Between Preexisting Heart Failure With Reduced Ejection Fraction And Fluid Administration Among Patients With Sepsis, Rachel E Powell, Jason N Kennedy, Mourad H Senussi, Ian J Barbash, Christopher W Seymour

Faculty, Staff and Students Publications

IMPORTANCE: Intravenous fluid administration is recommended to improve outcomes for patients with septic shock. However, there are few data on fluid administration for patients with preexisting heart failure with reduced ejection fraction (HFrEF).

OBJECTIVE: To evaluate the association between preexisting HFrEF, guideline-recommended intravenous fluid resuscitation, and mortality among patients with community-acquired sepsis and septic shock.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted of adult patients hospitalized in an integrated health care system from January 1, 2013, to December 31, 2015, with community-acquired sepsis and preexisting assessment of cardiac function. Follow-up occurred through July 1, 2016. Data analyses were …

Dietary Interventions For Gastroparesis: A Systematic Review, Debra Eseonu, Tanya Su, Keya Lee, Bruno P Chumpitazi, Robert J Shulman, Ruben Hernaez

Faculty, Staff and Students Publications

Gastroparesis (Gp) is a delay in gastric emptying in the absence of a mechanical obstruction and has the capacity to cause symptoms that significantly impact a patient's quality of life. Dietary interventions are the first-line treatment in Gp, but the efficacy of different diets is unclear. This systematic review seeks to determine the effectiveness of dietary interventions on clinical outcomes in Gp. A literature search of MEDLINE Ovid from 1 March 2008 to 1 October 2021 was conducted to identify randomized controlled trials, cohort studies, and cross-sectional studies that reported dietary interventions in Gp. From the initial search, 2789 studies …

Low-Dose Immune Tolerance Induction In Children With Severe Hemophilia A With High-Titer Inhibitors: Type Of Factor 8 Mutation And Outcomes, Jie Sun, Zekun Li, Gang Li, Kun Huang, Di Ai, Guoqing Liu, Wanru Yao, Xingjuan Xie, Hao Gu, Yingzi Zhen, Zhenping Chen, Runhui Wu

Faculty, Staff and Student Publications

BACKGROUND: No studies evaluated the role of

OBJECTIVES: To explore the association between

METHODS: Children SHA with high-titer inhibitors who received low-dose ITI therapy at least for 1 year were included in this study. Based on the risk of inhibitor development,

RESULTS: Of 104 children included, 101 had

CONCLUSIONS: Types of

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Li, Rafet Basar, Guohui Wang, Enli Liu, Judy S Moyes, Li Li, Lucila N Kerbauy, Nadima Uprety, Mohsen Fathi, Ali Rezvan, Pinaki P Banerjee, Luis Muniz-Feliciano, Tamara J Laskowski, Emily Ensley, May Daher, Mayra Shanley, Mayela Mendt, Sunil Acharya, Bin Liu, Alexander Biederstädt, Hind Rafei, Xingliang Guo, Luciana Melo Garcia, Paul Lin, Sonny Ang, David Marin, Ken Chen, Laura Bover, Richard E Champlin, Navin Varadarajan, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted transfer of the CAR cognate antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their target, and (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen-expressing NK cells (NK

Perspectives Of Zambian Clinical Oncology Trainees In The Md Anderson And Zambia Virtual Clinical Research Training Program (Mozart), Kevin Diao, Darya A Kizub, Noveen Ausat, Catherine K Mwaba, Chidinma P Anakwenze Akinfenwa, Carrie A Cameron, Elizabeth Y Chiao, Dorothy C Lombe, Susan C Msadabwe, Lilie L Lin

Faculty, Staff and Student Publications

BACKGROUND: African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts.

MATERIALS AND METHODS: The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that …

Immune Checkpoint Inhibitors Have Clinical Activity In Patients With Recurrent Chordoma, Andrew J Bishop, Behrang Amini, Heather Lin, Shaan M Raza, Shreyaskumar Patel, David R Grosshans, Amol Ghia, Ahsan Farooqi, B Ashleigh Guadagnolo, Devarati Mitra, Kadir C Akdemir, Alexander J Lazar, Wei-Lien Wang, Christopher Alvarez-Breckenridge, Justin Bird, Laurence D Rhines, Neeta Somaiah, Anthony P Conley

Faculty, Staff and Student Publications

The aim of this study is to evaluate the outcomes and tolerance of immune checkpoint inhibitors (ICIs) for patients with recurrent chordoma. We reviewed the records of 17 patients with recurrent chordomas who received ICIs for progressing disease as part of their treatment between 2016 and 2020. Response was assessed using response evaluation criteria in solid tumors 1.1 criteria. The Kaplan-Meier method was used to estimate the duration of response, progression-free survival (PFS), and overall survival (OS). Clinical benefit was defined as having stable disease (SD), a partial response, or a complete response. The median follow-up from the start of …

Automated Extraction Of Anatomical Measurements From Temporal Bone Ct Imaging, Andy S Ding, Alexander Lu, Zhaoshuo Li, Deepa Galaiya, Masaru Ishii, Jeffrey H Siewerdsen, Russell H Taylor, Francis X Creighton

Faculty, Staff and Student Publications

OBJECTIVE: Proposed methods of minimally invasive and robot-assisted procedures within the temporal bone require measurements of surgically relevant distances and angles, which often require time-consuming manual segmentation of preoperative imaging. This study aims to describe an automatic segmentation and measurement extraction pipeline of temporal bone cone-beam computed tomography (CT) scans.

STUDY DESIGN: Descriptive study of temporal bone measurements.

SETTING: Academic institution.

METHODS: A propagation template composed of 16 temporal bone CT scans was formed with relevant anatomical structures and landmarks manually segmented. Next, 52 temporal bone CT scans were autonomously segmented using deformable registration techniques from the Advanced Normalization Tools …

Correlations Between Peripheral Levels Of Inflammatory Mediators And Frontolimbic Structures In Bipolar Disorder: An Exploratory Analysis, Satyajit Mohite, Haitham Salem, Thiago Cordeiro, Jonika Tannous, Benson Mwangi, Sudhakar Selvaraj, Jair C Soares, Marsal Sanches, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD.

METHODS: Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed …

The Hect Family Of E3 Ubiquitin Ligases And Pten, Min Sup Song, Pier Paolo Pandolfi

Faculty, Staff and Student Publications

Members of the HECT family of E3 ubiquitin ligases have emerged as prominent regulators of PTEN function, subcellular localization and levels. In turn this unfolding regulatory network is allowing for the identification of genes directly involved in both tumorigenesis at large and cancer susceptibility syndromes. While the complexity of this regulatory network is still being unraveled, these new findings are paving the way for novel therapeutic modalities for cancer prevention and therapy as well as for other diseases. Here we will review the signal transduction and therapeutic implications of the cross-talk between HECT family members and PTEN.

Machine Learning Modeling Of Protein-Intrinsic Features Predicts Tractability Of Targeted Protein Degradation, Wubing Zhang, Shourya S Roy Burman, Jiaye Chen, Katherine A Donovan, Yang Cao, Chelsea Shu, Boning Zhang, Zexian Zeng, Shengqing Gu, Yi Zhang, Dian Li, Eric S Fischer, Collin Tokheim, X Shirley Liu

Faculty, Staff and Student Publications

Targeted protein degradation (TPD) has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell’s endogenous protein degradation machinery. However, the susceptibility of proteins for targeting by TPD approaches, termed “degradability”, is largely unknown. Here, we developed a machine learning model, model-free analysis of protein degradability (MAPD), to predict degradability from features intrinsic to protein targets. MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds [with an area under the precision–recall curve (AUPRC) of 0.759 and an area under the receiver operating characteristic curve (AUROC) of 0.775] and is …

Dosimetric Analysis Of Mr-Linac Treatment Plans For Salvage Spine Sbrt Re-Irradiation, Eun Young Han, Debra N Yeboa, Tina M Briere, Jinzhong Yang, He Wang

Faculty, Staff and Student Publications

PURPOSE: We investigated the feasibility of thoracic spine stereotactic body radiotherapy (SBRT) using the Elekta Unity magnetic resonance-guided linear accelerator (MRL) in patients who received prior radiotherapy. We hypothesized that Monaco treatment plans can improve the gross tumor volume minimum dose (GTVmin) with spinal cord preservation and maintain consistent plan quality during daily adaptation.

METHODS: Pinnacle clinical plans for 10 patients who underwent thoracic spine SBRT (after prior radiotherapy) were regenerated in the Monaco treatment planning system for the Elekta Unity MRL using 9 and 13 intensity-modulated radiotherapy (IMRT) beams. Monaco adapt-to-position (ATP) and adapt-to-shape (ATS) workflow plans were generated …

Efficacy And Safety Of A Single Dose Of Casirivimab And Imdevimab For The Prevention Of Covid-19 Over An 8-Month Period: A Randomised, Double-Blind, Placebo-Controlled Trial, Gary A Herman, Meagan P O'Brien, Eduardo Forleo-Neto, Neena Sarkar, Flonza Isa, Peijie Hou, Kuo-Chen Chan, Katharine J Bar, Ruanne V Barnabas, Dan H Barouch, Myron S Cohen, Christopher B Hurt, Dale R Burwen, Mary A Marovich, Bret J Musser, John D Davis, Kenneth C Turner, Adnan Mahmood, Andrea T Hooper, Jennifer D Hamilton, Janie Parrino, Danise Subramaniam, Alina Baum, Christos A Kyratsous, A Thomas Dicioccio, Neil Stahl, Ned Braunstein, George D Yancopoulos, David M Weinreich, Covid-19 Phase 3 Prevention Trial Team

Faculty, Staff and Student Publications

BACKGROUND: There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2-8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings.

METHODS: This was a randomised, …

Lenvatinib Plus Pembrolizumab In Japanese Patients With Endometrial Cancer: Results From Study 309/Keynote-775, Kan Yonemori, Mayu Yunokawa, Kimio Ushijima, Jun Sakata, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Takayuki Enomoto, Kazuhiro Takehara, Kosei Hasegawa, Wataru Yamagami, Keiko Yamamoto, Shirong Han, Lea Dutta, Robert Orlowski, Takuma Miura, Vicky Makker, Keiichi Fujiwara

Faculty, Staff and Student Publications

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m