Digital Commons Network^™

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

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 …

Molecular Pathways Of Major Depressive Disorder Converge On The Synapse, Gabriel R Fries, Valeria A Saldana, Johannes Finnstein, Theo Rein

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a psychiatric disease of still poorly understood molecular etiology. Extensive studies at different molecular levels point to a high complexity of numerous interrelated pathways as the underpinnings of depression. Major systems under consideration include monoamines, stress, neurotrophins and neurogenesis, excitatory and inhibitory neurotransmission, mitochondrial dysfunction, (epi)genetics, inflammation, the opioid system, myelination, and the gut-brain axis, among others. This review aims at illustrating how these multiple signaling pathways and systems may interact to provide a more comprehensive view of MDD's neurobiology. In particular, considering the pattern of synaptic activity as the closest physical representation of mood, …

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 …

Identification Of Minimum Essential Therapeutic Mixtures From Cannabis Plant Extracts By Screening In Cell And Animal Models Of Parkinson’S Disease, Michael G Morash, Jessica Nixon, Lori M N Shimoda, Helen Turner, Alexander J Stokes, Andrea L Small-Howard, Lee D Ellis

Faculty, Staff and Student Publications

Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson's disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an

Peripheral Blood Monocytes As A Therapeutic Target For Marrow Stromal Cells In Stroke Patients, Nikunj Satani, Kaushik Parsha, Courtney Davis, Adrian Gee, Scott D Olson, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: Systemic administration of marrow stromal cells

METHODS: Peripheral blood from stroke patients was collected at 5-7 days (

RESULTS: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared …

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 …

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 …

Synergistic Associations Of Pnpla3 I148m Variant, Alcohol Intake, And Obesity With Risk Of Cirrhosis, Hepatocellular Carcinoma, And Mortality, Hyun-Seok Kim, Xiangjun Xiao, Jinyoung Byun, Goo Jun, Stacia M Desantis, Han Chen, Aaron P Thrift, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Student Publications

IMPORTANCE: Alcohol drinking and obesity are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), but the risk is not uniform among people with these risk factors. Genetic variants, such as I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, may play an important role in modulating cirrhosis and HCC risk.

OBJECTIVE: to investigate the joint associations of the PNPLA3 I148M variant, alcohol intake, and obesity with the risk of cirrhosis, HCC, and liver disease-related mortality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 414 209 participants enrolled in the UK Biobank study from March 2006 …

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 …

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 …

Svat: Secure Outsourcing Of Variant Annotation And Genotype Aggregation, Miran Kim, Su Wang, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

BACKGROUND: Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions.

RESULTS: We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at …

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 …

A Randomized Controlled Trial Evaluating The Effects Of Social Networking On Chronic Disease Management In Rheumatoid Arthritis, Maria A Lopez-Olivo, Jessica T Foreman, Cheuk Leung, Heather Y Lin, Tiffany Westrich-Robertson, Catherine Hofstetter, Jude K A Des Bordes, Anne Lyddiatt, Amye Leong, Irmgard U Willcockson, Susan K Peterson, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVE: Social networking has been shown to improve health outcomes in certain patient populations. While patients with rheumatoid arthritis (RA) increasingly use social networking to communicate with peers, the effects of these interactions are largely unknown.

METHODS: In a randomized controlled trial, we compared RA patients who participated in a social networking group moderated by peer leaders and who had access to a static website offering RA materials with a control group, who only had access to the website. The primary outcomes were patients' RA knowledge, self-efficacy and empowerment. Secondary outcomes included participation in desired health behaviors, and satisfaction with …

Immunogenomic Profiling Of Lung Adenocarcinoma Reveals Poorly Differentiated Tumors Are Associated With An Immunogenic Tumor Microenvironment, Neal Akhave, Jiexin Zhang, Erin Bayley, Meredith Frank, Shin-Heng Chiou, Carmen Behrens, Runzhe Chen, Xin Hu, Edwin Roger Parra, Won-Chul Lee, Stephen Swisher, Luisa Solis, Annikka Weissferdt, Cesar Moran, Neda Kalhor, Jianhua Zhang, Paul Scheet, Ara A Vaporciyan, Boris Sepesi, Don L Gibbons, John V Heymach, Jack J Lee, Ignacio I Wistuba, P Andrew Futreal, Jianjun Zhang, Junya Fujimoto, Alexandre Reuben

Faculty, Staff and Student Publications

OBJECTIVES: Pathologists have routinely observed distinct histologic patterns of growth in early-stage lung adenocarcinoma (LUAD), which have been suggested to be associated with prognosis. Herein, we investigated the relationship between LUAD patterns of growth, as defined by the updated international association for the study of lung cancer (IASLC) grading criteria, and differences in the tumor immune microenvironment to identify predictors of response to immunotherapy.

METHODS: 174 resected stage I-III LUAD tumors were classified by histologic pattern of growth (i.e. solid, micropapillary, acinar, papillary, and lepidic) and then grouped as well differentiated, moderately differentiated, and poorly differentiated. Comprehensive multiplatform analysis including …

Indications For Absorbable Steroid-Eluting Sinus Implants: Viewpoint Via The Delphi Method, Victoria S Lee, Prayag Patel, Daniel O'Brien, George A Scangas, Raewyn G Campbell, Rakesh Chandra, Greg E Davis, Joseph K Han, Christopher H Le, Jivianne Lee, Amber U Luong, David M Poetker, Hassan Ramadan, Michael Setzen, Kristine Smith, Sarah Wise, Jennifer Villwock, Elisabeth Ference

Faculty, Staff and Student Publications

Absorbable steroid-eluting sinus implants provide targeted corticosteroid release over a sustained period and are designed to prevent both undesirable adhesion formation and sinus ostia restenosis. Here, we highlight the key evidence of these implants to date and query a group of experts via a Delphi process on the indications and optimal timing for intraoperative or in-office placement of these implants. Six of a total of 12 statements reached consensus and were accepted. Overall, experts largely agree that intraoperative or in-office use of steroid-eluting stents could be considered for patients: (1) who are diabetic or intolerant of oral steroids, (2) undergoing …

The Circular Rna Edis Regulates Neurodevelopment And Innate Immunity, Xiao-Peng Xiong, Weihong Liang, Wei Liu, Shiyu Xu, Jian-Liang Li, Antonio Tito, Julia Situ, Daniel Martinez, Chunlai Wu, Ranjan J Perera, Sheng Zhang, Rui Zhou

Faculty, Staff and Student Publications

Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We identify and validate a collection of circRNAs in Drosophila, and show that depletion of the brain-enriched circRNA Edis (circ_Ect4) causes hyperactivation of antibacterial innate immunity both in cultured cells and in vivo. Notably, Edis depleted flies display heightened resistance to bacterial infection and enhanced pathogen clearance. Conversely, ectopic Edis expression blocks innate immunity signaling. In addition, inactivation of Edis in vivo leads to impaired locomotor activity and shortened lifespan. Remarkably, these phenotypes can be recapitulated with neuron-specific depletion of Edis, accompanied by defective …