Medical Specialties Commons^™

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

Cell-Free Dna Concentration As A Biomarker Of Response And Recurrence In Her2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy, Mark Jesus M Magbanua, Ziad Ahmed, Rosalyn W Sayaman, Lamorna Brown Swigart, Gillian L Hirst, Christina Yau, Denise M Wolf, Wen Li, Amy L Delson, Jane Perlmutter, Paula Pohlmann, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J Esserman, Angela M Demichele, Hope S Rugo, Laura J Van 'T Veer

Faculty, Staff and Student Publications

Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.

Experimental design: 145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.

Results: In TNBC, we observed a modest negative correlation between cfDNA concentration 3 …

Efficacy And Safety Of Adagrasib Plus Cetuximab In Patients With Krasg12c-Mutated Metastatic Colorectal Cancer, Rona Yaeger, Nataliya V Uboha, Meredith S Pelster, Tanios S Bekaii-Saab, Minal Barve, Joel Saltzman, Joshua K Sabari, Julio A Peguero, Andrew Scott Paulson, Pasi A Jänne, Marcia Cruz-Correa, Kenna Anderes, Karen Velastegui, Xiaohong Yan, Hirak Der-Torossian, Samuel J Klempner, Scott E Kopetz

Faculty, Staff and Student Publications

Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2-7.6). Median progression-free survival was 6.9 months …

Telomere Dysfunction Alters Intestinal Stem Cell Dynamics To Promote Cancer, Kyle A Labella, Wen-Hao Hsu, Jiexi Li, Yutao Qi, Yonghong Liu, Jingjing Liu, Chia-Chin Wu, Yang Liu, Zingzhi Song, Yiyun Lin, Jonathan M Blecher, Shan Jiang, Xiaoying Shang, Jincheng Han, Denise J Spring, Jianhua Zhang, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, …

Taro: Tree-Aggregated Factor Regression For Microbiome Data Integration, Aditya K Mishra, Iqbal Mahmud, Philip L Lorenzi, Robert R Jenq, Jennifer A Wargo, Nadim J Ajami, Christine B Peterson

Faculty, Staff and Student Publications

MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.

RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information …

Phosphatidylserine Regulates Plasma Membrane Repair Through Tetraspanin-Enriched Macrodomains, Yang E Li, Dougall M Norris, Fanqian N Xiao, Elvis Pandzic, Renee M Whan, Sandra Fok, Ming Zhou, Guangwei Du, Yang Liu, Ximing Du, Hongyuan Yang

Faculty, Staff and Student Publications

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from …

Update On Cancer Predisposition Syndromes And Surveillance Guidelines For Childhood Brain Tumors, Jordan R Hansford, Anirban Das, Rose B Mcgee, Yoshiko Nakano, Jack Brzezinski, Sarah R Scollon, Surya P Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C Greer, Rosanna Weksberg, Douglas R Stewart, William D Foulkes, Uri Tabori, Kristian W Pajtler, Stefan M Pfister, Garrett M Brodeur, Junne Kamihara

Faculty, Staff and Students Publications

Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease etiology increases. Some children with brain tumors may present with nonmalignant phenotypic features of specific syndromes (e.g., nevoid basal cell carcinoma syndrome, neurofibromatosis type 1 and type 2, DICER1 syndrome, and constitutional mismatch-repair deficiency), while others may present with a strong family history of cancer (e.g., Li-Fraumeni syndrome) or with a rare tumor commonly found in the context of germline predisposition (e.g., rhabdoid tumor predisposition …

Strength Of Selection In Lung Tumors Correlates With Clinical Features Better Than Tumor Mutation Burden, Ivan P Gorlov, Olga Y Gorlova, Spyridon Tsavachidis, Christopher I Amos

Faculty, Staff and Students Publications

Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations …

Differentiation Between Descending Thoracic Aortic Diseases Using Machine Learning And Plasma Proteomic Signatures, Amanda Momenzadeh, Simion Kreimer, Dongchuan Guo, Matthew Ayres, Daniel Berman, Kuang-Yuh Chyu, Prediman K Shah, Dianna Milewicz, Ali Azizzadeh, Jesse G Meyer, Sarah Parker

Faculty, Staff and Student Publications

BACKGROUND: Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

METHODS: This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter …

Real-World Multiple Myeloma Risk Factors And Outcomes By Non-Hispanic Black/African American And Non- Hispanic White Race/Ethnicity In The United States., Tondre Buck, Monique A Hartley-Brown, Yvonne A Efebera, Carter P Milner, Jeffrey A Zonder, Paul G Richardson, Taylor Salinardi, Megan S Rice

Oncology Articles

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the US. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White …

Differential Expression Of Wnt5a Long And Short Isoforms In Non-Muscle-Invasive Bladder Urothelial Carcinoma., Amy M Strope, Cody Phillips, Sabin Khadgi, Scott A Jenkinson, Karen T Coschigano, Ramiro Malgor

Oncology Articles

Wnt ligands belong to a family of secreted glycoproteins in which binding to a range of receptors/co-receptors activates several intracellular pathways. WNT5A, a member of the Wnt family, is classified as a non-canonical Wnt whose activation triggers planar cell polarity (PCP) and Ca+2 downstream pathways. Aberrant expression of WNT5A has been shown to play both protective and harmful roles in an array of conditions, such as inflammatory disease and cancer. In the present study, using histological, immunohistochemical, and molecular methods, we investigated the expression of two isoforms of WNT5A, WNT5A-Short (WNT5A-S) and WNT5A-Long (WNT5A-L) in bladder urothelial carcinoma (UC). Three …

Post Hoc Analysis Of Daratumumab Plus Lenalidomide, Bortezomib And Dexamethasone In Black Patients From Final Data Of The Griffin Study., Ajay K Nooka, Jonathan L Kaufman, Cesar Rodriguez, Andrzej Jakubowiak, Yvonne Efebera, Brandi Reeves, Tanya M Wildes, Sarah A Holstein, Larry D Anderson, Ashraf Badros, Leyla Shune, Ajai Chari, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Oncology Articles

Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients.

Pediatric Cancers And Family Financial Toxicity In The Philippines: Insights For Southeast Asia And Similarly Resourced Settings, Rod Carlo Columbres, Erin Jay G. Feliciano, Kathleen Joy Taleon-Tampo, Katelyn Edelwina Y. Legaspi, Michelle Ann B. Eala, Kenrick Ng, Fumiko Chino, Frederic Ivan L. Ting, Edward Christopher Dee

Ateneo School of Medicine and Public Health Publications

Cancer is a leading cause of death among children in the Philippines, a low-middle-income country of over 110 million people. In this Comment, we describe how financial toxicity affects families of pediatric patients with cancer in the Philippines. We explore direct costs of care, indirect costs such as transportation and lodging, and psychosocial sequelae, in the Filipino medical system and sociocultural contexts. We present examples of successful interventions in the Philippines and in similarly resourced settings, with the goal of galvanizing further research, clinical interventions, and policy-level changes, aimed at mitigating family financial toxicity for pediatric patients with cancer in …

Radiogenomics-Based Risk Prediction Of Glioblastoma Multiforme With Clinical Relevance, Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D Chan, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed …

Thyroid Cartilage Metastases From Prostate Cancer On 18f Psma Pet Ct: A Case Series, Poonamjeet Loyal, Samuel Gitau, Khalid Makhdomi

Imaging & Diagnostic Radiology, East Africa

Prostate cancer metastases to the thyroid cartilage is an extremely rare phenomenon. We report three cases of advanced prostate carcinoma with metastases to the thyroid cartilage identified on 18F prostate-specific membrane antigen-1007 (PSMA-1007) positron emission tomography (PET)/computed tomography (CT). The pathophysiology and possibility for under-reporting are also discussed. Prostate cancer metastases to the larynx should be considered in the differential diagnosis of thyroid cartilage lesions in patients with advanced prostate cancer and is associated with poor prognosis.

3d Bioprinting The Tumor Microenvironment For Immunotherapy Development, Molly Leyda, Tykeem Manor, John Szarejko, Douglas Myers, John M. Perry

Posters

The tumor microenvironment (TME) is a complex system that plays a crucial role in tumor progression, immune evasion, and therapy resistance. The TME is composed of various cell types, including tumor cells, stromal cells, and immune cells such as macrophages. Macrophages are versatile myeloid cells which can exhibit both pro-tumoral and anti-tumoral functions, depending on their phenotype and the TME context. M1 macrophages have demonstrated promising pro-inflammatory and anti-tumor effects, while tumor associated M2 macrophages (TAMs) play an anti-inflammatory role and promote tumor immune escape. Understanding the complex interactions between TAMs and the TME is, therefore, essential for developing effective …

Unresectable Cardiac Metastasis From Melanoma Responds Well To Combination Immunotherapy - A Case Report, Ek Leone Oh, Peter Dias, Zeyad Al-Ogaili, Jacobus Otto, Lydia Warburton

Research outputs 2022 to 2026

Background: Melanoma can metastasize to distal organs including the heart although presentation with a symptomatic cardiac metastasis is rare. The optimal management remains uncertain particularly in the era of immunotherapy. Case summary: We report a case presenting with a large unresectable cardiac metastasis from melanoma that responded well to treatment with immunotherapy. Conclusion: Melanoma can metastasize to the heart and is often challenging to diagnose. Combination immunotherapy can be an effective treatment option even in the setting of a symptomatic and unresectable cardiac metastasis.

A Multisite Initiative To Increase Utilization Of Clinical Pathways In The Selection Of Systemic Cancer Treatment, Kate Hough

2024 Swedish Learning and Celebration Day

No abstract provided.

From Pre-Clinical To Translational Brain Metastasis Research: Current Challenges And Emerging Opportunities, Emilija Aleksandrovic, Siyuan Zhang, Dihua Yu

Faculty, Staff and Student Publications

Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical interventions have remained elusive. The heterogeneous nature of the primary tumor of origin, complications in drug delivery across the blood-brain barrier, and the distinct microenvironment collectively pose formidable clinical challenges in developing new treatments for patients with brain metastasis. Although current preclinical models have deepened our basic understanding of the disease, much of the existing research on brain metastasis has employed a reductionist approach. This approach, which often relies on either in vitro systems or in …

Associations Between Longer Leukocyte Telomere Length And Increased Lung Cancer Risk Among Never Smokers In Urban China, Jason Y Y Wong, Xiao-Ou Shu, Wei Hu, Batel Blechter, Jianxin Shi, Kevin Wang, Richard Cawthon, Qiuyin Cai, Gong Yang, Mohammad L Rahman, Bu-Tian Ji, Yutang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology.

METHODS: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control …

Barriers To The Assessment And Recommendation Of Hpv Vaccination Among Healthcare Providers In Texas, Onyema G Chido-Amajuoyi, Ikponmwosa Osaghae, Henry K Onyeaka, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Healthcare providers (HCPs) recommendations for HPV vaccination plays a critical role in increasing vaccination uptake. This study assesses the prevalence of reported barriers to HPV vaccination assessment and recommendation among HCPs in Texas.

METHODS: Study data were obtained from a population-based survey of HCPs currently practicing in Texas. Participants were asked about their HPV vaccination assessment and recommendation practices and the reasons for not assessing or recommending the vaccine. Barriers were stratified by HCP characteristics including age, sex, race/ethnicity, location of practice, provider type, and type of facility.

RESULTS: Among the 826 HCPs included in this study, 47.3 % …

A Prismatic View Of The Epigenetic-Metabolic Regulatory Axis In Breast Cancer Therapy Resistance, Chandrima Das, Apoorva Bhattacharya, Swagata Adhikari, Atanu Mondal, Payel Mondal, Santanu Adhikary, Siddhartha Roy, Kenneth Ramos, Kamlesh K Yadav, John A Tainer, Tej K Pandita

Faculty, Staff and Student Publications

Epigenetic regulation established during development to maintain patterns of transcriptional expression and silencing for metabolism and other fundamental cell processes can be reprogrammed in cancer, providing a molecular mechanism for persistent alterations in phenotype. Metabolic deregulation and reprogramming are thus an emerging hallmark of cancer with opportunities for molecular classification as a critical preliminary step for precision therapeutic intervention. Yet, acquisition of therapy resistance against most conventional treatment regimens coupled with tumor relapse, continue to pose unsolved problems for precision healthcare, as exemplified in breast cancer where existing data informs both cancer genotype and phenotype. Furthermore, epigenetic reprograming of the …

Understanding The Treatment Paradigm And The Sequencing Of Antiglaucoma Fixed-Dose Combinations In A Tertiary Center In South India, Ronnie George, Praggya Mishra, Balekudaru Shantha, Lingam Vijaya, Nitin Maksane, Neha Gurha

Faculty, Staff and Student Publications

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India.

METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications …

Clinical Features And Genomic Epidemiology Of Bloodstream Infections Due To Enterococcal Species Other Than Enterococcus Faecalis Or E Faecium In Patients With Cancer, Dierdre B Axell-House, Patrycja A Ashley, Stephanie L Egge, Truc T Tran, Claudia Pedroza, Meng Zhang, An Q Dinh, Shelby R Simar, Pranoti V Sahasrabhojane, William R Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Non–Enterococcus faecium, non–E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.

METHODS: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood cultureclearance). Whole-genome sequencing was performed on all …

Duration Of Androgen Deprivation Therapy With Postoperative Radiotherapy For Prostate Cancer: A Comparison Of Long-Course Versus Short-Course Androgen Deprivation Therapy In The Radicals-Hd Randomised Trial, Chris C Parker, Howard Kynaston, Adrian D Cook, Noel W Clarke, Charles N Catton, William R Cross, Peter M Petersen, Rajendra A Persad, Cheryl A Pugh, Fred Saad, John Logue, Heather Payne, Lorna C Bower, Chris Brawley, Mary Rauchenberger, Maroie Barkati, David M Bottomley, Klaus Brasso, Hans T Chung, Peter W M Chung, Ruth Conroy, Alison Falconer, Vicky Ford, Chee L Goh, Catherine M Heath, Nicholas D James, Charmaine Kim-Sing, Ravi Kodavatiganti, Shawn C Malone, Stephen L Morris, Abdenour Nabid, Aldrich D Ong, Rakesh Raman, Sree Rodda, Paula Wells, Jane Worlding, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes

Faculty, Staff and Student Publications

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.

METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT …

Mash: Mediation Analysis Of Survival Outcome And High-Dimensional Omics Mediators With Application To Complex Diseases, Sunyi Chi, Christopher R Flowers, Ziyi Li, Xuelin Huang, Peng Wei

Faculty, Staff and Student Publications

Environmental exposures such as cigarette smoking influence health outcomes through intermediate molecular phenotypes, such as the methylome, transcriptome, and metabolome. Mediation analysis is a useful tool for investigating the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposures and health outcomes. However, little work has been done on mediation analysis when the mediators are high-dimensional and the outcome is a survival endpoint, and none of it has provided a robust measure of total mediation effect. To this end, we propose an estimation procedure for Mediation Analysis of Survival outcome and High-dimensional omics mediators (MASH) based on sure …

International Consensus Guidelines For The Definition, Detection, And Interpretation Of Autophagy-Dependent Ferroptosis, Xin Chen, Andrey S Tsvetkov, Han-Ming Shen, Ciro Isidoro, Nicholas T Ktistakis, Andreas Linkermann, Werner J H Koopman, Hans-Uwe Simon, Lorenzo Galluzzi, Shouqing Luo, Daqian Xu, Wei Gu, Olivier Peulen, Qian Cai, David C Rubinsztein, Jen-Tsan Chi, Donna D Zhang, Changfeng Li, Shinya Toyokuni, Jinbao Liu, Jong-Lyel Roh, Enyong Dai, Gabor Juhasz, Wei Liu, Jianhua Zhang, Minghua Yang, Jiao Liu, Ling-Qiang Zhu, Weiping Zou, Mauro Piacentini, Wen-Xing Ding, Zhenyu Yue, Yangchun Xie, Morten Petersen, David A Gewirtz, Michael A Mandell, Charleen T Chu, Debasish Sinha, Eftekhar Eftekharpour, Boris Zhivotovsky, Sébastien Besteiro, Dmitry I Gabrilovich, Do-Hyung Kim, Valerian E Kagan, Hülya Bayir, Guang-Chao Chen, Scott Ayton, Jan D Lünemann, Masaaki Komatsu, Stefan Krautwald, Ben Loos, Eric H Baehrecke, Jiayi Wang, Jon D Lane, Junichi Sadoshima, Wan Seok Yang, Minghui Gao, Christian Münz, Michael Thumm, Martin Kampmann, Di Yu, Marta M Lipinski, Jace W Jones, Xuejun Jiang, Herbert J Zeh, Rui Kang, Daniel J Klionsky, Guido Kroemer, Daolin Tang

Faculty, Staff and Student Publications

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense …

The Combination Of Tumor Mutational Burden And T-Cell Receptor Repertoire Predicts The Response To Immunotherapy In Patients With Advanced Non-Small Cell Lung Cancer, Yalun Li, Liyan Ji, Yingqian Zhang, Jiexin Zhang, Alexandre Reuben, Hao Zeng, Qin Huang, Qi Wei, Sihan Tan, Xuefeng Xia, Weimin Li, Jianjun Zhang, Panwen Tian

Faculty, Staff and Student Publications

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (

Longitudinal Changes In The Carotid Arteries Of Head And Neck Cancer Patients Following Radiation Therapy: Results From A Prospective Serial Imaging Biomarker Characterization Study, Efstratios Koutroumpakis, Abdallah Sherif Radwan Mohamed, Peter Chaftari, David I Rosenthal, Dorothy Gujral, Christopher Nutting, Serageldin Kamel, Mohamed A Naser, Peter Kim, Roland Bassett, Clifton D Fuller, Elie Mouhayar, Md Anderson Head Neck Radiation Oncology Cardiovascular Working Group

Faculty, Staff and Student Publications

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; …

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …