Medical Specialties Commons^™

Clinical And Biological Significance Of Circulating Mirnas In Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation, Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin

Faculty, Staff and Student Publications

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.

Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.

Results: …

Correspondence On "Points To Consider In The Practice Of Postmortem Genetic Testing: A Statement Of The American College Of Medical Genetics And Genomics (Acmg)" By Deignan, Et Al, Fowzan S Alkuraya, Kathryn J Gray, Siddharth K Prakash, Monica H Wojcik, Angela E Lin

Faculty, Staff and Student Publications

No abstract provided.

Joint Vestibular Schwannoma Enlargement Prediction And Segmentation Using A Deep Multi-Task Model, Kai Wang, Nicholas A George-Jones, Liyuan Chen, Jacob B Hunter, Jing Wang

Faculty, Staff and Student Publications

Objective: To develop a deep-learning-based multi-task (DMT) model for joint tumor enlargement prediction (TEP) and automatic tumor segmentation (TS) for vestibular schwannoma (VS) patients using their initial diagnostic contrast-enhanced T1-weighted (ceT1) magnetic resonance images (MRIs).

Methods: Initial ceT1 MRIs for VS patients meeting the inclusion/exclusion criteria of this study were retrospectively collected. VSs on the initial MRIs and their first follow-up scans were manually contoured. Tumor volume and enlargement ratio were measured based on expert contours. A DMT model was constructed for jointly TS and TEP. The manually segmented VS volume on the initial scan and the tumor enlargement label …

Suspected Bronchiectasis And Mortality In Adults With A History Of Smoking Who Have Normal And Impaired Lung Function : A Cohort Study, Alejandro A Diaz, Wei Wang, Jose L Orejas, Rim Elalami, Wojciech R Dolliver, Pietro Nardelli, Ruben San José Estépar, Bina Choi, Carrie L Pistenmaa, James C Ross, Diego J Maselli, Andrew Yen, Kendra A Young, Gregory L Kinney, Michael H Cho, Raul San José Estépar

Faculty, Staff and Student Publications

Background: Bronchiectasis in adults with chronic obstructive pulmonary disease (COPD) is associated with greater mortality. However, whether suspected bronchiectasis-defined as incidental bronchiectasis on computed tomography (CT) images plus clinical manifestation-is associated with increased mortality in adults with a history of smoking with normal spirometry and preserved ratio impaired spirometry (PRISm) is unknown.

Objective: To determine the association between suspected bronchiectasis and mortality in adults with normal spirometry, PRISm, and obstructive spirometry.

Design: Prospective, observational cohort.

Setting: The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study.

Participants: 7662 non-Hispanic Black or White adults, aged 45 to 80 years, with 10 …

Advances In Vaccine Development For Cancer Prevention And Treatment In Lynch Syndrome, Ana M Bolivar, Fahriye Duzagac, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal …

Emerging Therapeutics And Evolving Assessment Criteria For Intracranial Metastases In Patients With Oncogene-Driven Non-Small-Cell Lung Cancer, Kelsey Pan, Kyle Concannon, Jing Li, Jianjun Zhang, John V Heymach, Xiuning Le

Faculty, Staff and Student Publications

The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood-brain barrier. However, …

Cancer Germline Predisposing Variants And Late Mortality From Subsequent Malignant Neoplasms Among Long-Term Childhood Cancer Survivors: A Report From The St Jude Lifetime Cohort And The Childhood Cancer Survivor Study, Cheng Chen, Na Qin, Mingjuan Wang, Qian Dong, Saima Sultana Tithi, Yawei Hui, Wenan Chen, Gang Wu, Dennis Kennetz, Michael N Edmonson, Michael C Rusch, Andrew Thrasher, John Easton, Heather L Mulder, Nan Song, Noel-Marie Plonski, Kyla Shelton, Cindy Im, Matthew J Ehrhardt, Kim E Nichols, Wendy M Leisenring, Kayla L Stratton, Rebecca Howell, Yutaka Yasui, Smita Bhatia, Gregory T Armstrong, Kirsten K Ness, Melissa M Hudson, Jinghui Zhang, Hui Wang, Deo Kumar Srivastava, Leslie L Robison, Zhaoming Wang

Faculty, Staff and Student Publications

Background: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis).

Methods: In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or …

Trends In Radiation Dose To The Contralateral Breast During Breast Cancer Radiation Therapy, Gordon P Watt, Susan A Smith, Rebecca M Howell, Angélica Pérez-Andújar, Ann S Reiner, Laura Cerviño, Beryl Mccormick, Daniela Hess, Julia A Knight, Kathleen E Malone, Esther M John, Leslie Bernstein, Charles F Lynch, Lene Mellemkjær, Roy E Shore, Xiaolin Liang, Meghan Woods, John D Boice, Lawrence T Dauer, Jonine L Bernstein

Faculty, Staff and Student Publications

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in …

Risk Factors For Overweight And Obesity After Childhood Acute Lymphoblastic Leukemia In North America And Switzerland: A Comparison Of Two Cohort Studies, Fabiën N Belle, Christina Schindera, Marc Ansari, Gregory T Armstrong, Maja Beck-Popovic, Rebecca Howell, Wendy M Leisenring, Lillian R Meacham, Jochen Rössler, Ben D Spycher, Emily Tonorezos, Nicolas X Von Der Weid, Yutaka Yasui, Kevin C Oeffinger, Claudia E Kuehni

Faculty, Staff and Student Publications

Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors.

Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in …

Kras G12c In Advanced Nsclc: Prevalence, Co-Mutations, And Testing, Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M Kerr, Myung-Ju Ahn, Joshua R Kapp, Fernando A Soares, Yasushi Yatabe

Faculty, Staff and Student Publications

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence …

International Association For The Study Of Lung Cancer Study Of Reproducibility In Assessment Of Pathologic Response In Resected Lung Cancers After Neoadjuvant Therapy, Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A Schalper, Ming-Sound Tsao, David P Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A Bunn, Mark G Kris, Chandra P Belani, Karen Kelly, Ignacio Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable …

Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir

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The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.

Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan

Faculty, Staff and Student Publications

Medical device technology develops rapidly, and the life cycle of a medical device is much shorter than drugs. It is necessary to evaluate the safety and effectiveness of a medical device in a timely manner to keep up with technology flux. Bayesian methods provides an efficient approach to addressing this challenge. In this article, we review the characteristics of the Bayesian approach and some Bayesian designs that were commonly used in medical device regulatory setting, including Bayesian adaptive design, Bayesian diagnostic design, Bayesian multiregional design, and Bayesian label expansion study. We illustrate these designs with medical devices approved by the …

Medication Reconciliation During Transitions Of Care Across Institutions: A Quantitative Analysis Of Challenges And Opportunities, Alejandro Araya, Logan R Thornton, Deukwoo Kwon, Gayla M Ferguson, Linda D Highfield, Kevin O Hwang, Holly M Holmes, Elmer V Bernstam

Faculty, Staff and Student Publications

OBJECTIVE: Medication discrepancies between clinical systems may pose a patient safety hazard. In this paper, we identify challenges and quantify medication discrepancies across transitions of care.

METHODS: We used structured clinical data and free-text hospital discharge summaries to compare active medications' lists at four time points: preadmission (outpatient), at-admission (inpatient), at-discharge (inpatient), and postdischarge (outpatient). Medication lists were normalized to RxNorm. RxNorm identifiers were further processed using the RxNav API to identify the ingredient. The specific drugs and ingredients from inpatient and outpatient medication lists were compared.

RESULTS: Using RxNorm drugs, the median percentage intersection when comparing active medication lists …

Dynamics Of The Dynll1-Mre11 Complex Regulate Dna End Resection And Recruitment Of Shieldin To Dsbs, Michelle L Swift, Rui Zhou, Aleem Syed, Lisa A Moreau, Bartłomiej Tomasik, John A Tainer, Panagiotis A Konstantinopoulos, Alan D D'Andrea, Yizhou Joseph He, Dipanjan Chowdhury

Faculty, Staff and Student Publications

The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by …

Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.

METHODS: Primary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting …

Anchors: A Way For Ftsz Filaments To Stay Membrane Bound, Arindam Naha, Daniel P Haeusser, William Margolin

Faculty, Staff and Student Publications

Most bacteria use the tubulin homolog FtsZ to organize their cell division. FtsZ polymers initially assemble into mobile complexes that circle around a ring-like structure at the cell midpoint, followed by the recruitment of other proteins that will constrict the cytoplasmic membrane and synthesize septal peptidoglycan to divide the cell. Despite the need for FtsZ polymers to associate with the membrane, FtsZ lacks intrinsic membrane binding ability. Consequently, FtsZ polymers have evolved to interact with the membrane through adaptor proteins that both bind FtsZ and the membrane. Here, we discuss recent progress in understanding the functions of these FtsZ membrane …

Automated Contouring And Statistical Process Control For Plan Quality In A Breast Clinical Trial, Hana Baroudi, Callistus I Huy Minh Nguyen, Sean Maroongroge, Benjamin D Smith, Joshua S Niedzielski, Simona F Shaitelman, Adam Melancon, Sanjay Shete, Thomas J Whitaker, Melissa P Mitchell, Isidora Yvonne Arzu, Jack Duryea, Soleil Hernandez, Daniel El Basha, Raymond Mumme, Tucker Netherton, Karen Hoffman, Laurence Court

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Automatic review of breast plan quality for clinical trials is time-consuming and has some unique challenges due to the lack of target contours for some planning techniques. We propose using an auto-contouring model and statistical process control to independently assess planning consistency in retrospective data from a breast radiotherapy clinical trial.

MATERIALS AND METHODS: A deep learning auto-contouring model was created and tested quantitatively and qualitatively on 104 post-lumpectomy patients' computed tomography images (nnUNet; train/test: 80/20). The auto-contouring model was then applied to 127 patients enrolled in a clinical trial. Statistical process control was used to assess …

Basic: A Bayesian Adaptive Synthetic-Control Design For Phase Ii Clinical Trials, Liyun Jiang, Peter F Thall, Fangrong Yan, Scott Kopetz, Ying Yuan

Faculty, Staff and Student Publications

Background: Randomized controlled trials are considered the gold standard for evaluating experimental treatments but often require large sample sizes. Single-arm trials require smaller sample sizes but are subject to bias when using historical control data for comparative inferences. This article presents a Bayesian adaptive synthetic-control design that exploits historical control data to create a hybrid of a single-arm trial and a randomized controlled trial.

Methods: The Bayesian adaptive synthetic control design has two stages. In stage 1, a prespecified number of patients are enrolled in a single arm given the experimental treatment. Based on the stage 1 data, applying propensity …

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …

Rare Variants Found In Clinical Gene Panels Illuminate The Genetic And Allelic Architecture Of Orofacial Clefting, Kimberly K Diaz Perez, Sarah W Curtis, Alba Sanchis-Juan, Xuefang Zhao, Taylor Head, Samantha Ho, Bridget Carter, Toby Mchenry, Madison R Bishop, Luz C Valencia-Ramirez, Claudia Restrepo, Jacqueline T Hecht, Lina M Uribe, George Wehby, Seth M Weinberg, Terri H Beaty, Jeffrey C Murray, Eleanor Feingold, Mary L Marazita, David J Cutler, Michael P Epstein, Harrison Brand, Elizabeth J Leslie

Faculty, Staff and Student Publications

PURPOSE: Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.

METHODS: We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.

RESULTS: 9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance.

CONCLUSION: …

Dietary Intake And Quality Among Stroke Survivors: Nhanes 1999-2018, Erika R Zoellner, Mindy A Patterson, Anjail Z Sharrief, Sean I Savitz, Wesley J Tucker, Derek C Miketinas

Faculty, Staff and Student Publications

Background: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited.

Objectives: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke.

Methods: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of …

Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman

Faculty, Staff and Student Publications

No abstract provided.

Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. …

Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor

Faculty, Staff and Student Publications

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and …

Characteristics And Outcomes Of Patients With Chronic Myeloid Leukemia And T315i Mutation Treated In The Pre- And Post-Ponatinib Era, Fadi G Haddad, Koji Sasaki, Aram Bidikian, Ghayas C Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Patients with chronic myeloid leukemia (CML) and T315I mutation generally have a poor prognosis. Their outcome in the post-ponatinib era remains unclear. We reviewed patients with CML in chronic (CP) or accelerated phase (AP) who developed a T315I mutation between March 15, 2004, and July 26, 2022. Patients were divided into CP, AP, or blastic phase (BP) at the time of mutation detection. Overall survival (OS) was defined from the time of mutation detection to the date of death or last follow-up. We identified a total of 107 patients: 54 (51%) in CP, 14 (13%) in AP, and 39 (36%) …

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …

Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang

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Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments …

Local Continual Reassessment Methods For Dose Finding And Optimization In Drug-Combination Trials, Jingyi Zhang, Fangrong Yan, Nolan A Wages, Ruitao Lin

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Due to the limited sample size and large dose exploration space, obtaining a desirable dose combination is a challenging task in the early development of combination treatments for cancer patients. Most existing designs for optimizing the dose combination are model-based, requiring significant efforts to elicit parameters or prior distributions. Model-based designs also rely on intensive model calibration and may yield unstable performance in the case of model misspecification or sparse data. We propose to employ local, underparameterized models for dose exploration to reduce the hurdle of model calibration and enhance the design robustness. Building upon the framework of the partial …