Medical Specialties Commons^™

Tntdetectai: A Deep Learning Model For Automated Detection And Counting Of Tunneling Nanotubes In Microscopy Images, Yasin Ceran, Hamza Ergüder, Katherine Ladner, Sophie Korenfeld, Karina Deniz, Sanyukta Padmanabhan, Phillip Wong, Murat Baday, Thomas Pengo, Emil Lou, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND: Tunneling nanotubes (TNTs) are cellular structures connecting cell membranes and mediating intercellular communication. TNTs are manually identified and counted by a trained investigator; however, this process is time-intensive. We therefore sought to develop an automated approach for quantitative analysis of TNTs.

METHODS: We used a convolutional neural network (U-Net) deep learning model to segment phase contrast microscopy images of both cancer and non-cancer cells. Our method was composed of preprocessing and model development. We developed a new preprocessing method to label TNTs on a pixel-wise basis. Two sequential models were employed to detect TNTs. First, we identified the regions …

Guidelines For Assessing And Enhancing The Organizational Vitality Of Pharmacy Educational Programs: A Call To Action!, Ashim Malhotra, Jeremy Hughes, David G Fuentes

Faculty, Staff and Student Publications

Organizational vitality encompasses organizational mission and identity, organizational purpose and values, and employee engagement, cohesiveness, anxiety, and information sharing. Using the organizational vitality framework consisting of the following five pillars: (1) human, (2) knowledge, (3) intellectual, (4) financial capital, and (5) market value, we propose a reflection guide and specific calls to action for academic leaders including deans, department chairs, assistant/associate deans, and others within pharmacy and healthcare education systems. Our overall aim is to provide a blueprint for academic leaders to assess and enhance the organizational health, vitality, resiliency, and sustainability of their pharmacy educational programs using an established …

Critical Role Of Lncepat In Coupling Dysregulated Egfr Pathway And Histone H2a Deubiquitination During Glioblastoma Tumorigenesis, Linlin Li, Aidong Zhou, Yanjun Wei, Feng Liu, Peng Li, Runping Fang, Li Ma, Sicong Zhang, Longqiang Wang, Jinze Liu, Hope T Richard, Yiwen Chen, Hengbin Wang, Suyun Huang

Faculty, Staff and Student Publications

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16's recruitment to …

Lineage-Coupled Clonal Capture Identifies Clonal Evolution Mechanisms And Vulnerabilities Of Brafv600e Inhibition Resistance In Melanoma, Ze-Yan Zhang, Yingwen Ding, Ravesanker Ezhilarasan, Tenzin Lhakhang, Qianghu Wang, Jie Yang, Aram S Modrek, Hua Zhang, Aristotelis Tsirigos, Andrew Futreal, Giulio F Draetta, Roel G W Verhaak, Erik P Sulman

Faculty, Staff and Student Publications

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed "CAPTURE", a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAF

Lineage-Coupled Clonal Capture Identifies Clonal Evolution Mechanisms And Vulnerabilities Of Braf V600e Inhibition Resistance In Melanoma, Ze-Yan Zhang, Yingwen Ding, Ravesanker Ezhilarasan, Tenzin Lhakhang, Qianghu Wang, Jie Yang, Aram S Modrek, Hua Zhang, Aristotelis Tsirigos, Andrew Futreal, Giulio F Draetta, Roel G W Verhaak, Erik P Sulman

Faculty, Staff and Student Publications

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed "CAPTURE", a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAFV600E melanoma. Further integrative studies uncovered diverse resistance mechanisms. This includes a previously unrecognized and clinically relevant mechanism, chromosome 18q21 gain, which leads to vulnerability of the cells to BCL2 inhibitor. We also identified targetable …

Feasibility Of A Novel Non-Invasive Swab Technique For Serial Whole-Exome Sequencing Of Cervical Tumors During Chemoradiation Therapy, Julianna K Bronk, Chiraag Kapadia, Xiaogang Wu, Bhavana V Chapman, Rui Wang, Tatiana V Karpinets, Xingzhi Song, Andrew M Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Clinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to demonstrate the feasibility of a novel noninvasive cervical swab technique to (1) collect tumor DNA with adequate throughput to (2) perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT).

METHODS: Cervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were …

Complement Component C4 Structural Variation And Quantitative Traits Contribute To Sex-Biased Vulnerability In Systemic Sclerosis, Martin Kerick, Marialbert Acosta-Herrera, Carmen Pilar Simeón-Aznar, José Luis Callejas, Shervin Assassi, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Gianluca Moroncini, Jeska K De Vries-Bouwstra, Gisela Orozco, Anne Barton, Ariane L Herrick, Chikashi Terao, Yannick Allanore, Carmen Fonseca, Marta Eugenia Alarcón-Riquelme, Timothy R D J Radstake, Lorenzo Beretta, Christopher P Denton, Maureen D Mayes, Javier Martin

Faculty, Staff and Student Publications

Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its …

Single-Cell Sequencing Reveals Trajectory Of Tumor-Infiltrating Lymphocyte States In Pancreatic Cancer, Aislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara G Hughes, Alexandre Reuben, Shanshan Bai, Min Hu, Tapsi Kumar, Mark W Hurd, Matthew H G Katz, Ching-Wei D Tzeng, Shubham Pant, Milind Javle, David R Fogelman, Anirban Maitra, Cara L Haymaker, Michael P Kim, Nicholas E Navin, Chantale Bernatchez

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical …

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 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 …

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 …

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 …

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 …

Diagnostic Value Of Ultrasound In Children With Transverse Testicular Ectopia, Wei Zhou, Shoulin Li, Hao Wang, Jianchun Yin, Xiaodong Liu, Junhai Jiang, Guanglun Zhou, Jianguo Wen

Faculty, Staff and Student Publications

OBJECTIVE: The study aimed to investigate the diagnostic value of ultrasound in children's transverse testicular ectopia (TTE).

MATERIALS AND METHODS: We retrospectively studies all TTE cases diagnosed in our hospital from January 2017 to December 2021. All cases were evaluated by ultrasound examination and compared to physical examination and diagnostic laparoscopy results.

RESULTS: This study included 14 TTE patients in total, with a median age was 1.08 years. In the 14 TTE, physical examination found 10 TTE cases, of which nine testes were located in the opposite scrotum, one testis was located in the opposite groin, and the other four …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

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