Medicine and Health Sciences Commons^™

Exploring Illness Perceptions Of Multimorbidity Among Community-Dwelling Older Adults: A Mixed Methods Study, Ayomide Okanlawon Bankole, Rozmin B Jiwani, Forgive Avorgbedor, Jing Wang, Onome H Osokpo, Sara L Gill, Carrie Jo Braden

Faculty, Staff and Student Publications

Background: Illness perceptions are individual beliefs or experiences about the nature and treatment of their illness. Although extensive research exists about illness perceptions, little is known about illness perceptions of multimorbidity.

Methods: The purpose of this parallel-convergent mixed-methods study was to comprehensively explore illness perception of multimorbidity among community dwelling older adults. Data was collected using one-on-one semi-structured interviews (n=17) and the Multimorbidity Illness Perception Scale (MULTIPleS) (n=116). Qualitative data were analyzed using content analysis while quantitative data were analyzed with descriptive and inferential statistics. Both qualitative and quantitative findings were integrated to identify differences in illness perceptions of multimorbidity …

Acute Myeloid Leukemia With Mutated Tp53: Is This Newly Proposed Entity Oversimplifying A Complex Group Of Neoplasms?, Hong Fang, L Jeffery Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Radiation-Induced Innate Neutrophil Response In Tumor Is Mediated By The Cxcls/Cxcr2 Axis, Faya Zhang, Oscar Mulvaney, Erica Salcedo, Subrata Manna, James Z Zhu, Tao Wang, Chul Ahn, Laurentiu M Pop, Raquibul Hannan

Faculty, Staff and Student Publications

The early events that lead to the inflammatory and immune-modulatory effects of radiation therapy (RT) in the tumor microenvironment (TME) after its DNA damage response activating the innate DNA-sensing pathways are largely unknown. Neutrophilic infiltration into the TME in response to RT is an early innate inflammatory response that occurs within 24-48 h. Using two different syngeneic murine tumor models (RM-9 and MC-38), we demonstrated that CXCR2 blockade significantly reduced RT-induced neutrophilic infiltration. CXCR2 blockade showed the same effects on RT-induced tumor inhibition and host survival as direct neutrophil depletion. Neutrophils highly and preferentially expressed CXCR2 compared to other immune …

Outcomes Of Autologous Stem Cell Transplantation In Patients With Ultra-High-Risk Multiple Myeloma, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Adeel Masood, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM). This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT). We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by …

Management Strategies And Survival In Cutaneous B-Cell Lymphoma: A Population Based Study, Kyle Lauck, Areebah S Ahmad, Quoc-Bao D Nguyen, Zixi Yang, Suprateek Kundu, Auris O Huen

Faculty, Staff and Student Publications

No abstract provided.

Clinical And Molecular Characterization Of Long-Term Survivors With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Atezolizumab Plus Carboplatin And Etoposide, Stephen V Liu, Tony S K Mok, Barzin Y Nabet, Aaron S Mansfield, Richard De Boer, György Losonczy, Shunichi Sugawara, Rafal Dziadziuszko, Maciej Krzakowski, Alexey Smolin, Maximilian J Hochmair, Marina C Garassino, Carl M Gay, John V Heymach, Lauren A Byers, Sivuonthanh Lam, Andrés Cardona, Stefanie Morris, Leah Adler, David S Shames, Martin Reck

Faculty, Staff and Student Publications

Objectives: In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.

Materials and methods: Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months …

Evaluating Strength Of Recommendations For Commonly Administered Medications In Lactating Women, Yevgenia Y Fomina, John J Byrne, Catherine Y Spong

Faculty, Staff and Student Publications

Objective: To characterize the data on medications for lactating people in the LactMed database and evaluate the strength of the data for the most commonly administered medications in lactating women.

Methods: A retrospective analysis of all medications in the LactMed database in 12/2020 was performed. Each medication was classified into one of three categories: absent data, minimal-moderate data, strong data pertaining to safety in lactation. No data was defined as no available research studies associated with the medication. Minimal-moderate data was defined as absent research studies in one or more of the four LactMed categories: maternal drug levels, infant drug …

Competing Engagement Of Β-Arrestin Isoforms Balances Igf1r/P53 Signaling And Controls Melanoma Cell Chemotherapeutic Responsiveness, Sonia Cismas, Sylvya Pasca, Caitrin Crudden, Iara Trocoli Drakensjo, Naida Suleymanova, Simin Zhang, Benjamin Gebhard, Dawei Song, Shiyong Neo, Takashi Shibano, Terry J Smith, George A Calin, Ada Girnita, Leonard Girnita

Faculty, Staff and Student Publications

Constraints on the p53 tumor suppressor pathway have long been associated with the progression, therapeutic resistance, and poor prognosis of melanoma, the most aggressive form of skin cancer. Likewise, the insulin-like growth factor type 1 receptor (IGF1R) is recognized as an essential coordinator of transformation, proliferation, survival, and migration of melanoma cells. Given that β-arrestin (β-arr) system critically governs the anti/pro-tumorigenic p53/IGF1R signaling pathways through their common E3 ubiquitin-protein ligase MDM2, we explore whether unbalancing this system downstream of IGF1R can enhance the response of melanoma cells to chemotherapy. Altering β-arr expression demonstrated that both β-arr1-silencing and β-arr2-overexpression (-β-arr1/+β-arr2) facilitated …

Systematic Review And Meta-Analysis Of Immune Checkpoint Inhibitors As Single Agent Or In Combination With Chemotherapy In Early-Stage Non-Small Cell Lung Cancer: Impact Of Clinicopathological Factors And Indirect Comparison Between Treatment Strategies, Antonio Nuccio, Giuseppe Viscardi, Fabio Salomone, Alberto Servetto, Francesco Maria Venanzi, Silvia Teresa Riva, Sara Oresti, Francesca Rita Ogliari, Mariagrazia Viganò, Alessandra Bulotta, Robert Cameron, Alessandra Esposito, Jacobi Hines, Roberto Bianco, Michele Reni, Tina Cascone, Marina Chiara Garassino, Valter Torri, Giulia Veronesi, Michela Cinquini, Roberto Ferrara

Faculty, Staff and Student Publications

Background: In non-small cell lung cancer (NSCLC), the immune checkpoint inhibitors (ICI) revolution is rapidly moving from metastatic to early-stage, however, the impact of clinicopathological variables and optimal treatment sequencing remain unclear.

Methods: Randomized controlled trials (RCTs) in patients with early-stage NSCLC treated with ICI as single agent or in combination with platinum-based chemotherapy (PCT) were included. Primary outcomes were pathological complete response (pCR), event free survival (EFS) (neoadjuvant/perioperative), and disease-free survival (DFS) (adjuvant). Secondary outcomes were major pathological response (MPR), overall survival (OS), toxicity, surgical outcomes (neoadjuvant/perioperative); OS and toxicity (adjuvant). An additional secondary endpoint was to compare EFS …

Repeated Encounters For Actinic Keratoses In Medicare Patients: A Retrospective Cohort Study, Nasim Khalfe, Lucy J Navsaria, Yao Li, Malgorzata K Nowakowska, Carly F Stender, Candice L Hinkston, Sharon H Giordano, Sanjay S Shete, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Innovations, Advances, And Challenges In Precision Radiation Oncology Physics, Fada Guan, Lawrence Bronk, Jinbo Yue, Radhe Mohan, Zhe Chen

Faculty, Staff and Student Publications

No abstract provided.

A Retrospective Examination Of Pain In Acute Stroke At Hospital Discharge, Deniz Dishman, Tia Lal, Christin Silos, Luyao Chen, Xiaoqian Jiang, Jennifer Beauchamp, Seema Aggarwal, Charles Green, Sean I Savitz

Faculty, Staff and Student Publications

Objectives: Pain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors' function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls.

Materials and methods: Using discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted …

Corrigendum To “Epstein-Barr-Virus-Positive Large B-Cell Lymphoma Associated With Breast Implants: An Analysis Of Eight Patients Suggesting A Possible Pathogenetic Relationship” [Modern Pathology 34 (2021) 2154–2167], L Jeffrey Medeiros, Mario L Marques-Piubelli, Valentina F I Sangiorgio, Roberto Ruiz-Cordero, Francisco Vega, Andrew L Feldman, Jennifer R Chapman, Mark W Clemens, Kelly K Hunt, Mark G Evans, Christine Khoo, Stephen Lade, Mark Silberman, Jerzy Morkowski, Edward M Pina, Daniel C Mills, Christopher M Bates, Winston B Magno, Aliyah R Sohani, Beth A Sieling, Joseph M O'Donoghue, Chris M Bacon, Neill Patani, Despina Televantou, Suzanne D Turner, Laura Johnson, Fiona Macneill, Andrew C Wotherspoon, Swaminathan P Iyer, Luis E Malpica, Keyur P Patel, Jie Xu, Roberto N Miranda

Faculty, Staff and Student Publications

No abstract provided.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy In Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial, Yongwoo David Seo, Hailing Lu, Graeme Black, Kimberly Smythe, Yuexin Yu, Cynthia Hsu, Juliana Ng, Pedro Hermida De Viveiros, E Houston Warren, Brett A Schroeder, Ryan B O'Malley, Lee D Cranmer, Elizabeth T Loggers, Michael J Wagner, Lynn Bonham, Venu G Pillarisetty, Gabrielle Kane, Peter Berglund, Frank J Hsu, Xinlei Mi, Borislav A Alexiev, Robert H Pierce, Stanley R Riddell, Robin L Jones, Jan Ter Meulen, Edward Y Kim, Seth M Pollack

Faculty, Staff and Student Publications

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts.

Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions.

Design, setting, and participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis …

The Clinicopathologic Features And Molecular Signatures Of Blastoid High-Grade B Cell Lymphoma, Not Otherwise Specified, Lianqun Qiu, Pei Lin, Mahsa Khanlari, Jie Xu, Evan N Cohen, Sofia Garces, Roberto N Miranda, Wei Wang, Hong Fang, Carlos E Bueso-Ramos, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome.

Sam: Self-Adapting Mixture Prior To Dynamically Borrow Information From Historical Data In Clinical Trials, Peng Yang, Yuansong Zhao, Lei Nie, Jonathon Vallejo, Ying Yuan

Faculty, Staff and Student Publications

Mixture priors provide an intuitive way to incorporate historical data while accounting for potential prior-data conflict by combining an informative prior with a noninformative prior. However, prespecifying the mixing weight for each component remains a crucial challenge. Ideally, the mixing weight should reflect the degree of prior-data conflict, which is often unknown beforehand, posing a significant obstacle to the application and acceptance of mixture priors. To address this challenge, we introduce self-adapting mixture (SAM) priors that determine the mixing weight using likelihood ratio test statistics or Bayes factors. SAM priors are data-driven and self-adapting, favoring the informative (noninformative) prior component …

Localization, Tissue Biology, And T Cell State — Implications For Cancer Immunotherapy, Jason M Schenkel, Kristen E Pauken

Faculty, Staff and Student Publications

Tissue localization is a critical determinant of T cell immunity. CD8+ T cells are contact-dependent killers, which requires them to physically be within the tissue of interest to kill peptide-MHC class I-bearing target cells. Following their migration and extravasation into tissues, T cells receive many extrinsic cues from the local microenvironment, and these signals shape T cell differentiation, fate and function. Because major organ systems are variable in their functions and compositions, they apply disparate pressures on T cells to adapt to the local microenvironment. Additional complexity arises in the context of malignant lesions (either primary or metastatic), and this …

The New Nci Precision Medicine Trials, Lyndsay N Harris, Charles D Blanke, Harry P Erba, James M Ford, Robert J Gray, Michael L Leblanc, Siwen Hu-Lieskovan, Mark R Litzow, Selina M Luger, Funda Meric-Bernstam, Peter J O'Dwyer, Megan K D Othus, Katerina Politi, Lois E Shepherd, Carmen J Allegra, Helen X Chen, S Percy Ivy, Larissa A Korde, Richard F Little, Lisa M Mcshane, Jeffrey A Moscow, David R Patton, Magdalena Thurin, Laura M Yee, James H Doroshow

Faculty, Staff and Student Publications

Basket, umbrella, and platform trial designs (master protocols) have emerged over the last decade to study precision medicine approaches in oncology. First-generation trials like NCI-MATCH (Molecular Analysis for Therapy Choice) have proven the principle that studying targeted therapies on a large scale is feasible both from the laboratory and clinical perspectives. However, single-agent targeted therapies have shown limited ability to control metastatic disease, despite careful matching of drug to target. As such, newer approaches employing combinations of targeted therapy, or targeted therapy with standard therapies, need to be considered. The NCI has recently embarked on three second-generation precision medicine trials …

In Severe Alcohol-Related Hepatitis, Acute Kidney Injury Is Prevalent, Associated With Mortality Independent Of Liver Disease Severity, And Can Be Predicted Using Il-8 And Micro-Rnas, Luke D Tyson, Stephen Atkinson, Robert W Hunter, Michael Allison, Andrew Austin, James W Dear, Ewan Forrest, Tong Liu, Emma Lord, Steven Masson, Joao Nunes, Paul Richardson, Stephen D Ryder, Mark Wright, Mark Thursz, Nikhil Vergis

Faculty, Staff and Student Publications

BACKGROUND: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain.

AIMS: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date.

METHODS: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; …

Posterior-Scleritis: Case Report Of An Uncommon Immune-Related Adverse Event In The Treatment Of Advanced Endometrial Cancer, Brandon I Ing, Derek Kuhl, Deanna Glassman, Cynae A Johnson, Shrina Patel, Amir A Jazaeri

Faculty, Staff and Student Publications

As Immune checkpoint inhibitors are being expanded for use in gynecologic malignancies, rare immune-related adverse events are more frequently being reported. Here we describe a 63-year-old with Stage IIIB mismatch repair deficient uterine adenocarcinoma who underwent six cycles of carboplatin and paclitaxel with partial response but persistent disease. She was then started on single agent pembrolizumab. After six cycles of pembrolizumab, she developed bilateral vision changes and was diagnosed with posterior scleritis. Pembrolizumab was held and she was treated with oral prednisone, with rapid resolution of symptoms. One month after completion of prednisone, vision changes were again reported and she …

Effects Of Antiresorptive Medications On Tooth Root Formation And Tooth Eruption In Paediatric Patients, Yuki Arai, Jeryl D English, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

Tooth eruption is a pivotal milestone for children's growth and development. This process involves with the formation of the tooth root, the periodontal ligament (PDL) and the alveolar bone, as the tooth crown penetrates the bone and gingiva to enter the oral cavity. This review aims to outline current knowledge of the adverse dental effects of antiresorptive medications. Recently, paediatric indications for antiresorptive medications, such as bisphosphonates (BPs), have emerged, and these agents are increasingly used in children and adolescents to cure pathological bone resorption associated with bone diseases and cancers. Since tooth eruption is accompanied by osteoclastic bone resorption, …

Multi-Omics Analysis In Developmental Bone Biology, Yuki Matsushita, Azumi Noguchi, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

Single-cell omics and multi-omics have revolutionized our understanding of molecular and cellular biological processes at a single-cell level. In bone biology, the combination of single-cell RNA-sequencing analyses and in vivo lineage-tracing approaches has successfully identified multi-cellular diversity and dynamics of skeletal cells. This established a new concept that bone growth and regeneration are regulated by concerted actions of multiple types of skeletal stem cells, which reside in spatiotemporally distinct niches. One important subtype is endosteal stem cells that are particularly abundant in young bone marrow. The discovery of this new skeletal stem cell type has been facilitated by single-cell multi-omics, …

Hyperoxidized Prdx3 As A Specific Ferroptosis Marker, Yuelong Yan, Boyi Gan

Faculty, Staff and Student Publications

The lack of a reliable and specific marker for ferroptosis has hindered the advancement of treatments related to this cell death mechanism toward clinical application. A recent study published in Molecular Cell has identified hyperoxidized peroxiredoxin 3 (PRDX3) as a promising marker for ferroptosis, opening up new avenues for monitoring and targeting ferroptosis in disease treatment.

Pathomic Features Reveal Immune And Molecular Evolution From Lung Preneoplasia To Invasive Adenocarcinoma, Pingjun Chen, Frank R Rojas, Xin Hu, Alejandra Serrano, Bo Zhu, Hong Chen, Lingzhi Hong, Rukhmini Bandyoyadhyay, Muhammad Aminu, Neda Kalhor, J Jack Lee, Siba El Hussein, Joseph D Khoury, Harvey I Pass, Andre L Moreira, Vamsidhar Velcheti, Daniel H Sterman, Junya Fukuoka, Kazuhiro Tabata, Dan Su, Lisha Ying, Don L Gibbons, John V Heymach, Ignacio I Wistuba, Junya Fujimoto, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials …

Atm Mutations Associate With Distinct Co-Mutational Patterns And Therapeutic Vulnerabilities In Nsclc, Natalie I Vokes, Ana Galan Cobo, Margarita Fernandez-Chas, David Molkentine, Santiago Treviño, Vitaly Druker, Yu Qian, Sonia Patel, Stephanie Schmidt, Lingzhi Hong, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Marcelo V Negrao, Don L Gibbons, Ara Vaporciyan, Xiuning Le, Jia Wu, Jianjun Zhang, Una Rigney, Sonia Iyer, Emma Dean, John V Heymach

Faculty, Staff and Student Publications

PURPOSE: Ataxia-telangiectasia mutated (ATM) is the most frequently mutated DNA damage repair gene in non-small cell lung cancer (NSCLC). However, the molecular correlates of ATM mutations and their clinical implications have not been fully elucidated.

EXPERIMENTAL DESIGN: Clinicopathologic and genomic data from 26,587 patients with NSCLC from MD Anderson, public databases, and a de-identified nationwide (US-based) NSCLC clinicogenomic database (CGDB) were used to assess the co-mutation landscape, protein expression, and mutational processes in ATM-mutant tumors. We used the CGDB to evaluate ATM-associated outcomes in patients treated with immune checkpoint inhibitors (ICI) with or without chemotherapy, and assessed the effect of …

Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Urbi Roy, Anju Sharma, Meghana Manjunath, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness …

Role Of The Immune System In Liver Transplantation And Its Implications For Therapeutic Interventions, Guanrong Chen, Xin Hu, Yingchen Huang, Xiaonan Xiang, Sheng Pan, Ronggao Chen, Xiao Xu

Faculty, Staff and Student Publications

Liver transplantation (LT) stands as the gold standard for treating end-stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia-reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's …

Improving Radiotherapy In Immunosuppressive Microenvironments By Targeting Complement Receptor C5ar1, Callum Beach, David Maclean, Dominika Majorova, Stavros Melemenidis, Dhanya K Nambiar, Ryan K Kim, Gabriel N Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily Vs Hillson, Ashley K Mcculloch, Ross K Mcmahon, Kathryn Pennel, Joanne Edwards, Sean M O'Cathail, Campbell S Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C Koong, Trent M Woodruff, Edward E Graves, Tim Maughan, Simon Ja Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J Leedham, Amato J Giaccia, Monica M Olcina

Faculty, Staff and Student Publications

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased …

An Opioid-Minimizing Multimodal Pain Regimen Reduces Opioid Exposure And Pain In Trauma-Injured Patients At High Risk For Opioid Misuse: Secondary Analysis From The Mast Trial, Constanza De Dios, Robert Suchting, Charles Green, James M Klugh, John A Harvin, Heather E Webber, Joy M Schmitz, Scott D Lane, Jin H Yoon, Angela Heads, Kandice Motley, Angela Stotts

Faculty, Staff and Student Publications

BACKGROUND: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse.

METHODS: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original …

Influenza Viral Infection Is A Risk Factor For Severe Illness In Covid-19 Patients: A Nationwide Population-Based Cohort Study, Jeong-Hwan Hwang, Yeon Seok You, Sang Woo Yeom, Min Gyu Lee, Jong-Hwan Lee, Min Gul Kim, Jong Seung Kim

Faculty, Staff and Student Publications

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with …