Medical Specialties Commons^™

Individual Vmat Beam Complexity Indices Have Limited Predictive Value For Qa Pass-Rates, Jian Liang, Q Liu, David T. To, Michael G. Snyder

Conference Presentation Abstracts

Purpose: Previous studies with sample sizes <400 have indicated that VMAT beam complexity indices may have a relationship with measured QA pass-rates. The aim of this study is to evaluate such relationships on a large scale to further investigate their strength. Methods: Total of 17,273 VMAT QA results across 8 Elekta Agility machines were used in this study. All beams were flattened 6MV or 10MV. Sun Nuclear ArcCheck was used for QA measurements with γ-analysis parameters of 10% threshold, 3% dose difference, 2mm distance to agreement, and 95% passing threshold. A total 214 Beams (1.23%) failed QA. QA distributions in Pinnacle were calculated with 2 degree gantry intervals and a dose grid of 2mm. Four complexity indices (MCSv, MU weighted Segment Area, Segment Area/Perimeter, and Average Leaf Gap) were computed. Spearman’s correlations were evaluated for each, and cut-off values for the indices were sought to indicate values above which no QA failures would be expected. Results: Evaluation of the 4 complexity metrics showed weak correlation with QA pass rates (< ±0.42) with high significance (p < 0.001). When metrics were evaluated independently, cut-off values from correlation plots separated only 0.67%, 0.72%, 2.2%, 6.3% guaranteed passing beams from the total sample, respectively. When evaluating whether anymetric for a given beam exceeded its cut-off, the fraction of guaranteed passing beams rose to only 6.6%. However, when cut-off values for one metric were allowed to be functionally dependent upon another, the fraction of guaranteed passing beams increased. For MU weighted Segment Area andAverage Leaf Gap, a dependent approach separated 19.1% guaranteed passing beams from the sample. Conclusion: Individual complexity metrics have weak predictive utility in assessing plan performance. However, using multiple complexity cut-off functions with dependence upon more than one metric increased the fraction of predicted passing beams by around 300%.

Develop A Novel Beam Orientation Optimization Algorithm For Let (Linear Energy Transfer) Incorporated Impt (Intensity Modulated Proton Therapy) (Imptlet, R Dao, Y Qian, Xiaoqiang Li, H Quan, Xuanfeng Ding, G Liu

Conference Presentation Abstracts

Purpose: To improve the dose and LET distribution in the IMPTLET, we introduce a new optimization algorithm to search for the optimal beam orientation and count through the arc trajectory (BOC-IMPTLET). Methods: We introduce kmeans clustering analysis in the BOC-IMPTLET algorithm by analyzing the distribution of LET in the target from the full arc trajectory. The optimal of cluster count was used as beam count, which was determined based on the SSE (Sum of Square Error) value and the angle of the corresponding centroid of each cluster was used as beam orientation, respectively. The BOC-IMPTLET algorithm was implemented in the …

Linac-Based Srs Treatments Slow Down Unnecessarily Due To Parked Leaf Optimization, Brian Loughery, Cory S. Knill, Raminder P. Sandhu, Lifeng Lin, Jian Liang

Conference Presentation Abstracts

Purpose: It was observed on a VersaHD that clinical SRS deliveries created in the Elements treatment planning system (TPS) slowed gantry rotation and dose rate to allow parked MLC leaves to move into position for use in an upcoming control point. Gantry rotation slowed suddenly, visibly backtracking to previous gantry angles. The purpose of this work is to study the effect of parked MLC positioning parameters in Elements on cranial SRS delivery speed and gantry motion on a VersaHD. Methods: To study the effect of parked MLC leaf positions on VersaHD deliverability, cranial SRS plans were generated with different TPS …

The Clinical Usability, Efficiency, And Accuracy Of Combining Deep-Learning-Based Synthetic Ct And Auto-Contouring For Daily Cbct-Based Online Adaptive Radiation Therapy, An Qin, J Xu, N O'Connell, Xuanfeng Ding, Shupeng Chen, D Thill

Conference Presentation Abstracts

Purpose: To evaluate the feasibility of deep-learning and CBCT-based online adaptive radiotherapy(ART) in thorax, Head&Neck, and pelvic regions. Methods: The study utilized ADMIRE(Advanced Medical Image Registration Engine), a research software designed to enable fast online ART through: (1)synthetic CT(sCT) generation from CBCT, (2)automatic segmentation of critical organs(OARs), and(3)deformable image registration(DIR) to transfer the target volume. ADMIRE trained a modified Cycle-Generative-Adversarial-Networks with Structural Similarity Index Map(SSIM) loss term to generate sCT, while the auto-segmentation model was based on a 3D-ResUnet with modification. Site-specific models were trained for three anatomic sites: thorax, pelvic, and head&neck, and for both networks. The study included …

Derivation And Validation Of A Clinical Risk Assessment Model For Cancer-Associated Thrombosis In Two Unique Us Health Care Systems, Ang Li, Jennifer La, Sarah B May, Danielle Guffey, Wilson L Da Costa, Christopher I Amos, Raka Bandyo, Emily M Milner, Karen M Kurian, Daniel C R Chen, Nhan V Do, Carolina Granada, Nimrah Riaz, Mary T Brophy, Vipul Chitalia, J Michael Gaziano, David A Garcia, Marc Carrier, Christopher R Flowers, Neil A Zakai, Nathanael R Fillmore

Faculty, Staff and Students Publications

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy.

METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using …

Moderators Of Resistance-Based Exercise Programs' Effect On Sarcopenia-Related Measures In Men With Prostate Cancer Previously Or Currently Undergoing Androgen Deprivation Therapy: An Individual Patient Data Meta-Analysis, Pedro Lopez, Robert U. Newton, Dennis R. Taaffe, Kerri Winters-Stone, Daniel A. Galvão, Laurien M. Buffart

Research outputs 2022 to 2026

Introduction: Older men with prostate cancer are commonly affected by reductions in lean mass and physical function following androgen deprivation therapy (ADT). Resistance-based exercise programs are critical to counteract the musculoskeletal toxicities derived from prostate cancer treatment and aging. However, there is significant variability in the effects of exercise interventions. Examining demographic and clinical moderators of exercise effects in this patient group can assist in identifying which subgroups of patients benefit most. Therefore, we examined the effects and moderators of resistance-based exercise programs on sarcopenia-related outcomes that included lean mass, skeletal muscle index, physical function, and muscle strength in older …

Forging New Therapeutic Targets: Efforts Of Tumor Derived Exosomes To Prepare The Pre-Metastatic Niche For Cancer Cell Dissemination And Dormancy, Ranvir Bhatia, Joanna Chang, Jessian L Munoz, Nykia D Walker

Faculty, Staff and Students Publications

Tumor-derived exosomes play a multifaceted role in preparing the pre-metastatic niche, promoting cancer dissemination, and regulating cancer cell dormancy. A brief review of three types of cells implicated in metastasis and an overview of other types of extracellular vesicles related to metastasis are described. A central focus of this review is on how exosomes influence cancer progression throughout metastatic disease. Exosomes are crucial mediators of intercellular communication by transferring their cargo to recipient cells, modulating their behavior, and promoting tumor pro-gression. First, their functional role in cancer cell dissemination in the peripheral blood by facilitating the establishment of a pro-angiogenic …

Racial/Ethnic Disparities In Cervical Cancer Stage At Diagnosis: Mediating Effects Of Neighborhood-Level Socioeconomic Deprivation, Itunu O Sokale, Abiodun O Oluyomi, Jane R Montealegre, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Mortality from cervical cancer has declined steadily in the United States over the past several decades due to widespread screening for precancerous and early-stage cervical cancer (ECC), which are significantly easier to treat compared with late-stage cervical cancer (LCC). Unequal screening access continues to cause significant racial/ethnic disparities in cervical cancer diagnosis stage. This study examined the underlying role of neighborhood-level socioeconomic disadvantage as a potential mediator of the association between race/ethnicity and cervical cancer diagnosis stage.

METHODS: We analyzed Texas Cancer Registry data for cervical cancer cases diagnosed among women ages 18 or older from 2010 to 2018. …

Genetic Studies Of Paired Metabolomes Reveal Enzymatic And Transport Processes At The Interface Of Plasma And Urine, Pascal Schlosser, Nora Scherer, Franziska Grundner-Culemann, Sara Monteiro-Martins, Stefan Haug, Inga Steinbrenner, Burulça Uluvar, Matthias Wuttke, Yurong Cheng, Arif B Ekici, Gergely Gyimesi, Edward D Karoly, Fruzsina Kotsis, Johanna Mielke, Maria F Gomez, Bing Yu, Morgan E Grams, Josef Coresh, Eric Boerwinkle, Michael Köttgen, Florian Kronenberg, Heike Meiselbach, Robert P Mohney, Shreeram Akilesh, Gckd Investigators, Miriam Schmidts, Matthias A Hediger, Ulla T Schultheiss, Kai-Uwe Eckardt, Peter J Oefner, Peggy Sekula, Yong Li, Anna Köttgen

Faculty, Staff and Students Publications

The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the …

Diverse Murine Vaccinations Reveal Distinct Antibody Classes To Target Fusion Peptide And Variation In Peptide Length To Improve Hiv Neutralization, Mallika Sastry, Anita Changela, Jason Gorman, Kai Xu, Gwo-Yu Chuang, Chen-Hsiang Shen, Cheng Cheng, Hui Geng, Sijy O'Dell, Li Ou, Reda Rawi, Mateo Reveiz, Guillaume B E Stewart-Jones, Shuishu Wang, Baoshan Zhang, Tongqing Zhou, Andrea Biju, Michael Chambers, Xuejun Chen, Angela R Corrigan, Bob C Lin, Mark K Louder, Krisha Mckee, Alexandra F Nazzari, Adam S Olia, Danealle K Parchment, Edward K Sarfo, Tyler Stephens, Jonathan Stuckey, Yaroslav Tsybovsky, Raffaello Verardi, Yiran Wang, Cheng-Yan Zheng, Yuling Chen, Nicole A Doria-Rose, Adrian B Mcdermott, John R Mascola, Peter D Kwong

Faculty, Staff and Student Publications

While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could neutralize ~30% of HIV-1 strains. To explore the ability of the murine immune system to generate cross-clade neutralizing antibodies and to investigate how higher breadth and potency might be achieved, we tested 17 prime-boost regimens that utilized diverse fusion peptide-carrier conjugates and HIV-1 envelope trimers with different fusion peptides. We observed priming in mice with fusion peptide-carrier conjugates of variable peptide length to elicit higher neutralizing responses, a result we …

Dissociation Protocols Used For Sarcoma Tissues Bias The Transcriptome Observed In Single-Cell And Single-Nucleus Rna Sequencing, Danh D Truong, Salah-Eddine Lamhamedi-Cherradi, Robert W Porter, Sandhya Krishnan, Jyothishmathi Swaminathan, Amber Gibson, Alexander J Lazar, J Andrew Livingston, Vidya Gopalakrishnan, Nancy Gordon, Najat C Daw, Nicholas E Navin, Richard Gorlick, Joseph A Ludwig

Faculty, Staff and Student Publications

BACKGROUND: Single-cell RNA-seq has emerged as an innovative technology used to study complex tissues and characterize cell types, states, and lineages at a single-cell level. Classification of bulk tumors by their individual cellular constituents has also created new opportunities to generate single-cell atlases for many organs, cancers, and developmental models. Despite the tremendous promise of this technology, recent evidence studying epithelial tissues and diverse carcinomas suggests the methods used for tissue processing, cell disaggregation, and preservation can significantly bias gene expression and alter the observed cell types. To determine whether sarcomas - tumors of mesenchymal origin - are subject to …

Heritable Aortic Root Aneurysms, Maral Ouzounian, Scott A Lemaire, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Hrd Effects On First-Line Adjuvant Chemotherapy And Parpi Maintenance Therapy In Chinese Ovarian Cancer Patients, Lei Li, Yu Gu, Mengpei Zhang, Xiaohua Shi, Zhe Li, Xinyun Xu, Tianqi Sun, Yu Dong, Chao Xue, Xiaoru Zhu, Ran Lv, Kai Jiao, Xuwo Ji, Li-Juan Wang, Yang Zhang, Zhiyong Liang, Ying Jin, Rutie Yin, Ming Wu, Han Liang

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526-0.899; …

A Clinical Practice Review Of Percutaneous Ethanol Injection For Thyroid Nodules: State Of The Art For Benign, Cystic Lesions, Robert D.E. Clark, Xinyi Luo, Peter P. Issa, Ralph P. Tufano, Emad Kandil

School of Medicine Faculty Publications

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited …

Improving Surgeon-Patient Communication In Thyroid Cancer Diagnosis And Treatment Discussions: A Narrative Review, Lauren Schlegel, Roberta S. Perry, Elizabeth Cottrill

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background and Objective: Patient experience is greatly influenced by physician-patient communication. Yet, unmet communication needs continue to be well documented in patients with thyroid cancer. This review discusses factors that may impact this communication and presents communication interventions that are currently being used with thyroid cancer patients.

Methods: A narrative review of articles on the physician-patient relationship and communication in thyroid cancer published between 1985 and 2022 was conducted through PubMed and Google. An additional review of the articles referenced in the bibliography of the included articles was performed.

Key Content and Findings: This review discusses communication components impacting the …

Enhanced Evasion Of Neutralizing Antibody Response By Omicron Xbb15, Ch11, And Ca31 Variants, Panke Qu, Julia N Faraone, John P Evans, Yi-Min Zheng, Claire Carlin, Mirela Anghelina, Patrick Stevens, Soledad Fernandez, Daniel Jones, Ashish R Panchal, Linda J Saif, Eugene M Oltz, Baoshan Zhang, Tongqing Zhou, Kai Xu, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and …

Optimization Of The Filler-And-Binder Mixing Ratio For Enhanced Mechanical Strength Of Carbon-Carbon Composites, Ji-Hong Kim, Hye-In Hwang, Ji-Sun Im

Faculty, Staff and Student Publications

In this paper, a method for optimizing the mixing ratio of filler coke and binder for high-strength carbon-carbon composites is proposed. Particle size distribution, specific surface area, and true density were analyzed to characterize the filler properties. The optimum binder mixing ratio was experimentally determined based on the filler properties. As the filler particle size was decreased, a higher binder mixing ratio was required to enhance the mechanical strength of the composite. When the d

Therapeutic Potential Of A Small-Molecule Stat3 Inhibitor In A Mouse Model Of Colitis, Prema Robinson, Kelsey Montoya, Emily Magness, Emma Rodriguez, Viviana Villalobos, Nikita Engineer, Peng Yang, Uddalak Bharadwaj, Thomas Kris Eckols, David John Tweardy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC). In the current studies, we used the dextran sodium sulfate (DSS) murine model of colitis, which is widely used in preclinical studies, to determine the contribution of STAT3 to IBD. STAT3 has two isoforms: (STAT3 α; which has pro-inflammatory and anti-apoptotic functions, and STAT3β; which attenuates the effects of STAT3α). In the current study, we determined the contribution of STAT3 to IBD across all tissues by examining DSS-induced colitis in mice that express only STAT3α and in mice treated with TTI-101, a direct small-molecule inhibitor of both isoforms …

Microfibril-Associated Protein 5 And The Regulation Of Skin Scar Formation, Chen Han, Trevor R Leonardo, Bruna Romana-Souza, Junhe Shi, Shalyn Keiser, Heidi Yuan, Mohamad Altakriti, Matthew J Ranzer, Sammy Ferri-Borgogno, Samuel C Mok, Timothy J Koh, Seok Jong Hong, Lin Chen, Luisa A Dipietro

Faculty, Staff and Student Publications

Many factors regulate scar formation, which yields a modified extracellular matrix (ECM). Among ECM components, microfibril-associated proteins have been minimally explored in the context of skin wound repair. Microfibril-associated protein 5 (MFAP5), a small 25 kD serine and threonine rich microfibril-associated protein, influences microfibril function and modulates major extracellular signaling pathways. Though known to be associated with fibrosis and angiogenesis in certain pathologies, MFAP5's role in wound healing is unknown. Using a murine model of skin wound repair, we found that MFAP5 is significantly expressed during the proliferative and remodeling phases of healing. Analysis of existing single-cell RNA-sequencing data from …

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, M M Fahd Qadir, Daniela Nasteska, Paula Mota De Sa, Caroline M Gorvin, Manuel Blandino-Rosano, Charles R Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N Sure, Siva S V P Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E Frigo, Xiaowen Liu, Prasad V Katakam, Wiebke Arlt, Jochen Buck, Lonny R Levin, Tony Hu, Jay Kolls, Charles F Burant, Alejandra Tomas, Matthew J Merrins, Debbie C Thurmond, Ernesto Bernal-Mizrachi, David J Hodson, Franck Mauvais-Jarvis

Faculty, Staff and Student Publications

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

Progesterone From Ovulatory Menstrual Cycles Is An Important Cause Of Breast Cancer, Herjan J T Coelingh Bennink, Iman J Schultz, Marcus Schmidt, V Craig Jordan, Paula Briggs, Jan F M Egberts, Kristina Gemzell-Danielsson, Ludwig Kiesel, Kirsten Kluivers, Jan Krijgh, Tommaso Simoncini, Frank Z Stanczyk, Robert D Langer

Faculty, Staff and Student Publications

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting …

The Metabolic Profile Of Young, Watered Chickpea Plants Can Be Used As A Biomarker To Predict Seed Number Under Terminal Drought, Sarah J Purdy, David Fuentes, Purushothaman Ramamoorthy, Christopher Nunn, Brent N Kaiser, Andrew Merchant

Faculty, Staff and Student Publications

Chickpea is the second-most-cultivated legume globally, with India and Australia being the two largest producers. In both of these locations, the crop is sown on residual summer soil moisture and left to grow on progressively depleting water content, finally maturing under terminal drought conditions. The metabolic profile of plants is commonly, correlatively associated with performance or stress responses, e.g., the accumulation of osmoprotective metabolites during cold stress. In animals and humans, metabolites are also prognostically used to predict the likelihood of an event (usually a disease) before it occurs, e.g., blood cholesterol and heart disease. We sought to discover metabolic …

Gastrulation Morphogenesis In Synthetic Systems, Alyssa A Emig, Margot L K Williams

Faculty, Staff and Students Publications

Recent advances in pluripotent stem cell culture allow researchers to generate not only most embryonic cell types, but also morphologies of many embryonic structures, entirely in vitro. This recreation of embryonic form from naïve cells, known as synthetic morphogenesis, has important implications for both developmental biology and regenerative medicine. However, the capacity of stem cell-based models to recapitulate the morphogenetic cell behaviors that shape natural embryos remains unclear. In this review, we explore several examples of synthetic morphogenesis, with a focus on models of gastrulation and surrounding stages. By varying cell types, source species, and culture conditions, researchers have recreated …

The Role Of Bispecific Antibodies In Relapsed Refractory Multiple Myeloma: A Systematic Review, Razwana Khanam, Omer S. Ashruf, Syed Hamza Bin Waqar, Zunairah Shah, Saba Batool, Rameesha Mehreen, Pranali Pachika, Zinath Roksana, Mohammad Ebad Ur Rehman, Faiz Anwer

Abington Jefferson Health Papers

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, …

Differential Gene Expression Of Fresh Tissue And Patient-Derived Explants’ Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role Of Il-6 And Mcp-1, Alshaimaa Tarek, Hossam Taha Mohamed, Aya Ali El-Sharkawy, Shrouk Khalaf El-Sayed, Jon Mark Hirshon, Wendy A Woodward, Mohamed El-Shinawi, Mona Mostafa Mohamed

Faculty, Staff and Student Publications

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome.

METHODS: Fifty …

Association Of Smoking And Respiratory Disease History With Pancreatic Pathologies Requiring Surgical Resection, Carolyn Ream, Matthew Sabitsky, Rachel Huang, Emma Hammelef, Theresa P. Yeo, Harish Lavu, Charles J. Yeo, Wilbur Bowne, Avinoam Nevler

Student Papers, Posters & Projects

Background: The purpose of this study was to examine the relationship between various respiratory conditions, including hypercapnic respiratory disease, and a multitude of resected pancreatic lesions. Methods: This retrospective case-control study queried a prospectively maintained database of patients who underwent pancreaticoduodenectomy between January 2015 and October 2021. Patient data, including smoking history, medical history, and pathology reports, were recorded. Patients with no smoking history and no concomitant respiratory conditions were designated as the control group. Results: A total of 723 patients with complete clinical and pathological data were identified. Male current smokers showed increased rates of PDAC (OR 2.33, 95% …

Measuring Symptom Burden In Patients With Cancer During A Pandemic: The Md Anderson Symptom Inventory For Covid-19 Mdasi-Covid, Loretta A Williams, Meagan S Whisenant, Tito R Mendoza, Angela E Peek, Donna Malveaux, Donna K Griffin, Darcy A Ponce, Bruno Palma Granwehr, Ajay Sheshadri, Katherine A Hutcheson, Sara M Ali, Susan K Peterson, John V Heymach, Charles S Cleeland, Ishwaria M Subbiah

Faculty, Staff and Student Publications

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer.

METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to …

Smarcb1 Regulates A Tfcp2l1-Myc Transcriptional Switch Promoting Renal Medullary Carcinoma Transformation And Ferroptosis Resistance, Bujamin H Vokshi, Guillaume Davidson, Nassim Tawanaie Pour Sedehi, Alexandra Helleux, Marc Rippinger, Alexandre R Haller, Justine Gantzer, Jonathan Thouvenin, Philippe Baltzinger, Rachida Bouarich, Valeria Manriquez, Sakina Zaidi, Priya Rao, Pavlos Msaouel, Xiaoping Su, Hervé Lang, Thibault Tricard, Véronique Lindner, Didier Surdez, Jean-Emmanuel Kurtz, Franck Bourdeaut, Nizar M Tannir, Irwin Davidson, Gabriel G Malouf

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic …

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …

Kras-Dependency In Pancreatic Ductal Adenocarcinoma: Mechanisms Of Escaping In Resistance To Kras Inhibitors And Perspectives Of Therapy, Enrico Gurreri, Giannicola Genovese, Luigi Perelli, Antonio Agostini, Geny Piro, Carmine Carbone, Giampaolo Tortora

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in oncology because of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein extremely difficult. KRAS regulates development, cell growth, epigenetically dysregulated differentiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial …