Medicine and Health Sciences Commons^™

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …

Immunotherapeutic Approaches For Treating Hepatocellular Carcinoma, Wanying Shen, Yujie Chen, Pan Lei, Marisela Sheldon, Yutong Sun, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Liver cancer is a life-threatening disease, and its incidence is increasing globally. The most common form of liver cancer is hepatocellular carcinoma (HCC). Approximately half of patients with HCC, especially those at advanced disease stages, receive systemic therapies, including the tyrosine kinase inhibitors sorafenib and lenvatinib. Over the past few years, immune checkpoint inhibitors (ICIs) have changed the landscape of HCC treatment. In particular, the combination therapy with atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) significantly improved survival benefits compared with sorafenib as a single agent, a finding that has stimulated further preclinical and clinical development of immunotherapeutic …

Deep Learning Models For Automated Assessment Of Breast Density Using Multiple Mammographic Image Types, Bastien Rigaud, Olena O Weaver, Jennifer B Dennison, Muhammad Awais, Brian M Anderson, Ting-Yu D Chiang, Wei T Yang, Jessica W T Leung, Samir M Hanash, Kristy K Brock

Faculty, Staff and Student Publications

Recently, convolutional neural network (CNN) models have been proposed to automate the assessment of breast density, breast cancer detection or risk stratification using single image modality. However, analysis of breast density using multiple mammographic types using clinical data has not been reported in the literature. In this study, we investigate pre-trained EfficientNetB0 deep learning (DL) models for automated assessment of breast density using multiple mammographic types with and without clinical information to improve reliability and versatility of reporting. 120,000 for-processing and for-presentation full-field digital mammograms (FFDM), digital breast tomosynthesis (DBT), and synthesized 2D images from 5032 women were retrospectively analyzed. …

The Immune Landscape Of Undifferentiated Pleomorphic Sarcoma, Rossana Lazcano, Carmelia M Barreto, Ruth Salazar, Fernando Carapeto, Raymond S Traweek, Cheuk H Leung, Swati Gite, Jay Mehta, Davis R Ingram, Khalida M Wani, Kim-Anh T Vu, Edwin R Parra, Wei Lu, Jianling Zhou, Russell G Witt, Brandon Cope, Prapassorn Thirasastr, Heather Y Lin, Christopher P Scally, Anthony P Conley, Ravin Ratan, J Andrew Livingston, Alexandra M Zarzour, Joseph Ludwig, Dejka Araujo, Vinod Ravi, Shreyaskumar Patel, Robert Benjamin, Jennifer Wargo, Ignacio I Wistuba, Neeta Somaiah, Christina L Roland, Emily Z Keung, Luisa Solis, Wei-Lien Wang, Alexander J Lazar, Elise F Nassif

Faculty, Staff and Student Publications

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) can be associated with a relatively dense immune infiltration. Immune checkpoint inhibitors (anti-PD1, anti-PDL1, and anti-CTLA4) are effective in 20% of UPS patients. We characterize the immune microenvironment of UPS and its association with oncologic outcomes.

MATERIAL AND METHODS: Surgically resected UPS samples were stained by immunohistochemistry (IHC) for the following: tumor-associated immune cells (CD3, CD8, CD163, CD20), immune checkpoints (stimulatory: OX40, ICOS; inhibitory: PD-L1, LAG3, IDO1, PD1), and the adenosine pathway (CD73, CD39). Sections were reviewed for the presence of lymphoid aggregates (LA). Clinical data were retrospectively obtained for all samples. The Wilcoxon rank-sum …

Neoadjuvant Toripalimab Combined With Gemcitabine And Cisplatin In Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma (Neotgp01): An Open Label, Single-Arm, Phase Ib Clinical Trial, Xiaotao Huang, Qiaodan Liu, Guihua Zhong, Yingpeng Peng, Ye Liu, Lizhong Liang, Haiyu Hong, Weineng Feng, Shuang Yang, Yaqin Zhang, Shiping Xian, Zhanyu Li, Yuling Zhou, Zhaoyuan Zhang, Wen Jiang, Jun Liang, Zhi-Gang Liu

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC.

MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and …

Preparation Of Core-Shell-Structured Rdx@Pvdf Microspheres With Improved Thermal Stability And Decreased Mechanical Sensitivity, Hulin Wu, Aifeng Jiang, Mengru Li, Yanyan Wang, Fangchao Zhao, Yanchun Li

Faculty, Staff and Student Publications

Reducing the sensitivity of high-energy simple explosives is the key technology in improving the practical application of high-energy insensitive powder. As the most widely used high-energy explosive, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is limited in application due to its high sensitivity. In this work, polyvinylidene fluoride (PVDF) was used as an energetic binder. Core-shell-structured RDX@PVDF microspheres are produced using electrospray assembly technology and fully characterized by thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, and mechanical sensitivity. Their thermal stability and mechanical sensitivity are directly related to the weight fraction of the added PVDF. Moreover, core-shell-structured RDX@PVDF microspheres …

Crossmodal Correspondences Between Basic Tastes And Visual Design Features: A Narrative Historical Review, Byron P Lee, Charles Spence

Faculty, Staff and Student Publications

People tend to associate abstract visual features with basic taste qualities. This narrative historical review critically evaluates the literature on these associations, often referred to as crossmodal correspondences, between basic tastes and visual design features such as color hue and shape curvilinearity. The patterns, discrepancies, and evolution in the development of the research are highlighted while the mappings that have been reported to date are summarized. The review also reflects on issues of cross-cultural validity and deviations in the matching patterns that are observed when correspondences are assessed with actual tastants versus with verbal stimuli. The various theories that have …

Evolution And Modulation Of Antigen-Specific T Cell Responses In Melanoma Patients, Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lönnberg, Anna Kreutzman, Katriina Peltola, Micaela Hernberg, Chunlin Wang, Cassian Yee, Harri Lähdesmäki, Mark M Davis, Satu Mustjoki

Faculty, Staff and Student Publications

Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory …

Ez Clear For Simple, Rapid, And Robust Mouse Whole Organ Clearing, Chih-Wei Hsu, Juan Cerda, Jason M Kirk, Williamson D Turner, Tara L Rasmussen, Carlos P Flores Suarez, Mary E Dickinson, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevent the widespread adoption of these methods. Here, we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hr in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, samples …

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 …

Dissection Of A Sensorimotor Circuit Underlying Pathogen Aversion In C Elegans, Adam Filipowicz, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

BACKGROUND: Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown.

RESULTS: Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops …

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 …

Metarnn: Differentiating Rare Pathogenic And Rare Benign Missense Snvs And Indels Using Deep Learning, Chang Li, Degui Zhi, Kai Wang, Xiaoming Liu

Faculty, Staff and Student Publications

Multiple computational approaches have been developed to improve our understanding of genetic variants. However, their ability to identify rare pathogenic variants from rare benign ones is still lacking. Using context annotations and deep learning methods, we present pathogenicity prediction models, MetaRNN and MetaRNN-indel, to help identify and prioritize rare nonsynonymous single nucleotide variants (nsSNVs) and non-frameshift insertion/deletions (nfINDELs). We use independent test sets to demonstrate that these new models outperform state-of-the-art competitors and achieve a more interpretable score distribution. Importantly, prediction scores from both models are comparable, enabling easy adoption of integrated genotype-phenotype association analysis methods. All pre-computed nsSNV scores …

Clinical Decision Support Malfunctions Related To Medication Routes: A Case Series, Adam Wright, Scott Nelson, David Rubins, Richard Schreiber, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: To identify common medication route-related causes of clinical decision support (CDS) malfunctions and best practices for avoiding them.

MATERIALS AND METHODS: Case series of medication route-related CDS malfunctions from diverse healthcare provider organizations.

RESULTS: Nine cases were identified and described, including both false-positive and false-negative alert scenarios. A common cause was the inclusion of nonsystemically available medication routes in value sets (eg, eye drops, ear drops, or topical preparations) when only systemically available routes were appropriate.

DISCUSSION: These value set errors are common, occur across healthcare provider organizations and electronic health record (EHR) systems, affect many different types of …

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 …

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

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, …