Biomedical Informatics Commons^™

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Editorial: Molecular Mechanisms And Targeted Therapies For Colorectal Cancer Vol Ii, Alessandro Passardi, David Gibbons, Antonio Mario Scanu, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Molecular Alterations In Idh-Mutant Astrocytoma: A Multi-Institutional Retrospective Study, Keng Lam, Hanim I Ozkizilkaya, Denái R Milton, Antonio Dono, Yajie Liu, Suprateek Kundu, Vinodh A Kumar, Jason M Johnson, Yoshua Esquenazi, Chirag B Patel, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial.

Methods: This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.

Results: We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), …

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

18 Kda Translocator Protein (Tspo) Is Upregulated In Rat Brain After Peripheral Nerve Injury And Downregulated By Diroximel Fumarate, Rafael A Cazuza, Sever M Zagrai, Anamaria R Grieco, Thomas D Avery, Andrew D Abell, Hsiao-Ying Wey, Marco L Loggia, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Approach To Determining Etiology Of Hypophosphatemia In A Patient With Coexisting Phosphaturic Mesenchymal Tumor And Fibrous Dysplasia, Madhuri D Patil, Sintawat Wangsiricharoen, Alexander J Lazar, Bryan Moon, John E Madewell, Michael T Collins, Theresa A Guise

Faculty, Staff and Student Publications

Dysregulated FGF23 production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia, various forms of rickets, and fibrous dysplasia (FD). Coexistence of 2 conditions that can increase FGF23 concentrations is rare. We report a case of a 79-yr-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence of …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Mmrt: Multimut Recursive Tree For Predicting Functional Effects Of High-Order Protein Variants From Low-Order Variants, Bryce Forrest, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

Protein sequences primarily determine their stability and functions. Mutations may occur at one, two, or three positions at the same time (low-order variants) or at multiple positions simultaneously (high-order variants), which affect protein functions. So far, low-order variants, such as single variants, double variants, and triple variants, have been well-studied through high-throughput experimental scanning techniques and computational prediction methods. However, research on high-order variants remains limited because of the difficulty of scanning an exponentially large number of potential variant combinations. Nonetheless, studying higher-order variants is crucial for understanding the pathogenesis of complex diseases, advancing protein engineering, and driving precision medicine. …

Enhancing The Utility Of Polygenic Scores In Alzheimer’S Disease Through Systematic Curation And Annotation, Savannah Mwesigwa, Yulin Dai, Nitesh Enduru, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Polygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer's Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.

Methods: In this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the "GWAS significant variants" (GWAS-SV) method with the GWAS Catalog and flagged redundant files and …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …

Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino

Faculty, Staff and Student Publications

Objective: To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.

Methods and analysis: In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Integrative Multi-Omics Approach For Improving Causal Gene Identification, Austin King, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex …

Peripheral Administration Of Blood From Tau Transgenic Animals Exacerbates Brain Tau-Associated Pathology, Laura Vegas-Gomez, Matias Pizarro, Jesus Garcia-Martin, Maria Angeles Arredondo-Alcala, Bianca Bustamante, Carolina Gonzalez-Silva, Soledad Matus, Rodrigo Diaz-Espinoza, Antonia Gutierrez, Rodrigo Morales, Claudia Duran-Aniotz, Ines Moreno-Gonzalez

Faculty, Staff and Student Publications

The accumulation of amyloid plaques and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD). While amyloid-beta propagation through prion-like mechanisms has been extensively studied in both central and peripheral pathways, the potential spreading of tau aggregates in the periphery remains largely unexplored. Emerging evidence suggests that hyperphosphorylated tau (ptau) aggregates may propagate beyond the central nervous system, as they have been detected in peripheral tissues and biological fluids from humans and mouse models of tauopathies. However, whether peripheral ptau aggregates or other factors associated to its accumulation contribute to brain pathology remains unclear. In this study, we investigate the …

Correspondence To Editorial 2 On "Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial", Sun Young Yim, Sung Hwan Lee, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt

Faculty, Staff and Student Publications

Background: Magnetic resonance (MR) guided radiation therapy combines high-resolution image capabilities of MRI with the precise targeting of radiation therapy. However, MRI does not provide the essential electron density information for accurate dose calculation, which limit the application of MRI. In this presented work, we evaluated the potential for Deep Learning (DL) based synthetic CT (sCT) generation using 3D MRI setup scans acquired during real-time adaptive MRI-guided radiation therapy.

Methods: We trained and evaluated a Cycle-consistent Generative Adversarial Network (Cycle-GAN) using paired MRI and deformably registered CT scan slices (dCT) in the context of real-time adaptive MRI-guided radiation therapy. Synthetic …

A Phase Ib/Ii Trial Of Neoadjuvant Neratinib Added To Standard Therapy In Patients With Her2-Positive Or Hr-Positive/Her2-Negative Inflammatory Breast Cancer (Including Stage Iii And Iv Disease), Bora Lim, Angela Marx, Megumi Kai, Angela Alexander, Roland Bassett, Wencai Ma, Jie Willey, Huiming Sun, Azadeh Nasrazadani, Mohammad M Mohammad, Jianhua Zhang, Anthony Lucci, Susie X Sun, Michael C Stauder, Gary J Whitman, Huong Le-Petross, Vicente Valero, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.

Objectives: To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in …