Life Sciences Commons^™

Small Molecules Targeting Micrornas: New Opportunities And Challenges In Precision Cancer Therapy, Ancuta Jurj, Beatrice Fontana, Gabriele Varani, George A Calin

Faculty, Staff and Student Publications

Noncoding RNAs, especially miRNAs, play a pivotal role in cancer initiation and metastasis, underscoring their susceptibility to precise modulation via small molecule inhibitors. This review examines the innovative strategy of targeting oncogenic miRNAs with small drug-like molecules, an approach that can reshape the cancer treatment landscape. We review the current understanding of the multifaceted roles of miRNAs in oncogenesis, highlighting emerging therapeutic paradigms that have the potential to expand cancer treatment options. As research on small molecule inhibitors of miRNA is still in its early stages, ongoing investigative efforts and the development of new technologies and chemical matter are essential …

Clinical Translation Of A Deep Learning Model Of Radiation-Induced Lymphopenia For Esophageal Cancer, Zongsheng Hu, Radhe Mohan, Yan Chu, Xiaochun Wang, Peter S N Van Rossum, Yiqing Chen, Madison E Grayson, Angela G Gearhardt, Clemens Grassberger, Degui Zhi, Brian P Hobbs, Steven H Lin, Wenhua Cao

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia is a common immune toxicity that adversely impacts treatment outcomes. We report here our approach to translate a deep-learning (DL) model developed to predict severe lymphopenia risk among esophageal cancer into a strategy for incorporating the immune system as an organ-at-risk (iOAR) to mitigate the risk.

MATERIALS AND METHODS: We conducted "virtual clinical trials" utilizing retrospective data for 10 intensity-modulated radiation therapy (IMRT) and 10 passively-scattered proton therapy (PSPT) esophageal cancer patients. For each patient, additional treatment plans of the modality other than the original were created employing standard-of-care (SOC) dose constraints. Predicted values of absolute lymphocyte …

Understanding, Diagnosing, And Treating Pancreatic Cancer From The Perspective Of Telomeres And Telomerase, Songting Shou, Yuanliang Li, Jiaqin Chen, Xing Zhang, Chuanlong Zhang, Xiaochen Jiang, Fudong Liu, Li Yi, Xiyuan Zhang, En Geer, Zhenqing Pu, Bo Pang

Faculty, Staff and Student Publications

Telomerase is associated with cellular aging, and its presence limits cellular lifespan. Telomerase by preventing telomere shortening can extend the number of cell divisions for cancer cells. In adult pancreatic cells, telomeres gradually shorten, while in precancerous lesions of cancer, telomeres in cells are usually significantly shortened. At this time, telomerase is still in an inactive state, and it is not until before and after the onset of cancer that telomerase is reactivated, causing cancer cells to proliferate. Methylation of the telomerase reverse transcriptase (TERT) promoter and regulation of telomerase by lactate dehydrogenase B (LDHB) is the mechanism of telomerase …

Beneficial Effects Of Lactobacillus Plantarum On Growth Performance, Immune Status, Antioxidant Function And Intestinal Microbiota In Broilers, Xiao Xiao, Tiantian Cui, Songke Qin, Tao Wang, Jinsong Liu, Lihan Sa, Yanping Wu, Yifan Zhong, Caimei Yang

Faculty, Staff and Student Publications

Lactobacillus plantarum (L. plantarum) has been globally regarded as antibiotic alternative in animal farming in the past few years. However, the potential function of L. plantarum in broilers has not been systemically explored. In this study, a total of 560 one-day-old yellow-feathered broilers were randomly divided into 3 groups, fed with basal diet and drank with L. plantarum HJZW08 (LP) at the concentration of 0 (CON), 1000 × 10^5 (LP1000), and 2000 × 10^5 CFU/L (LP2000) for 70 d. Results showed that the body weight (BW), average daily …

Hexarelin Modulates Stress Effects On Ghrelin System Activity In Growing Lambs, Krystina Pierzchała-Koziec, C. G. Scanes, Alina Gajewska

Political Science Faculty Publications and Presentations

Hexarelin modulates stress effects on ghrelin system activity in growing lambs. Folia Biologica (Kraków) 72 : 87-96. Hexarelin is a synthetic ligand for the growth hormone secretagogue receptor 1a (GHSR-1a), also known as the ghrelin receptor. Ghrelin and hexarelin have been observed to influence the HPA axis by increasing the circulating concentrations of both adrenocorticotropin and adrenal glucocorticoid in rats and humans. The aim of this study was to assess the effects of hexarelin on the ghrelin system and the growth hormone (GH)–insulin-like growth factor 1 (IGF-1) axis in lambs stressed by an emotional factor – isolation. The isolation stress …

The Effects Of Environmental Changes On The Biodiversity And Macroecological Patterns Of Bird Assemblages In The United States, Marlen Acosta Alamo

Dissertations, Theses, and Capstone Projects

The current restructuring of species assemblages and global loss of biodiversity result from species-specific responses to anthropogenic changes in climate and land cover. I investigated the effect of these two drivers on the seasonal distribution and biodiversity of birds in the United States and how human-induced habitat loss impacts macroecological patterns such as the species-area and the abundance-occupancy relationships. In Chapter 1, I examined the existence of a correlation between breeding and wintering geographic distributions of birds with different migratory strategies and the effect of changes in climate and the proportion of crop-pasture and urban land cover on this correlation. …

Development Of Collagen Mimetic Mini-Fibrils With Tunable Collagenase Susceptibility, Jui Chaugule

Dissertations, Theses, and Capstone Projects

Collagen fibrils are the primary molecular scaffold of all connective tissues and provide the essential support for cell migration and differentiation. Collagen fibrils represent one of the most complex molecular hierarchies: three polypeptide chains in Gly-Xaa-Yaa repeating amino acid sequences, first form the rod-shaped collagen triple helix. These triple helices further self-assemble laterally in a specific manner to form fibrils having the characteristic 67 nm axially repeating structure known as the D-period. Enzymatic digestion of collagen fibrils by matrix metalloproteinases (MMPs) is critical for several physiological processes and is of particular consequence during wound healing. Many of the mechanisms of …

Competitive And Noncompetitive Credit Assignment To Reward Cues In The Lateral Orbitofrontal Cortex, Mihwa Kang

Dissertations, Theses, and Capstone Projects

This dissertation investigates the mechanisms underlying variations in credit assignment to reward cues, with a focus on the lateral orbitofrontal cortex (lOFC). The lOFC has long been implicated in signaling reward expectancies, with controversy as to whether it signals the economic value of future outcomes, their sensory features to guide behavior or both. However, whether the lOFC signals the relative (competition-dependent) or absolute (contiguity-dependent) credit of cues is unknown. To address this, I employed a combination of novel behavioral assays, in-vivo electrophysiological recordings and optogenetic stimulation in rats. In Chapter 2, I tested the suitability of a self-initiating variant of …

Glycine, Serine, And Arginine Additions To Cobb 500 Female Broilers Fed Dietary Variations In Crude Protein, M. A. Anas, N.S.B.M. Atapattu, K. B. Nelson, S. W. Crafton, Michael T. Kidd

Poultry Science Faculty Publications and Presentations

This study investigated the effects of supplemental Gly, Ser, and Arg on growth performance, carcass traits, footpad dermatitis, and litter ammonia emission of broilers fed low-protein diets from 18 to 42 d of age. A total 576 one-day-old female Cobb 500 broilers were divided into 6 dietary treatments: 1) control, high CP (HCP 20%), 2) medium CP (MCP 18%), 3) low CP (LCP 16%), 4) LCP + 0.20% Gly+Ser, 5) LCP + 0.20% Arg, and 6) LCP + 0.20% Gly+Ser + 0.20% Arg. Although BW gain and feed intake were not affected by treatments, reducing CP to LCP (16% CP) …

Early 1,25-Dihydroxyvitamin D3-Glycosides Supplementation: An Efficient Feeding Strategy Against Bacterial Chondronecrosis With Osteomyelitis Lameness In Broilers Assessed By Using An Aerosol Transmission Model, Andi Asnayanti, Khawla Alharbi, Anh Dang Trieu Do, Layla Al-Mitib, Kathrin Buhler, Jan Dirk Van Der Klis, Javier Gonzalez, Michael T. Kidd, Adnan A. Alrubaye

Poultry Science Faculty Publications and Presentations

Bacterial chondronecrosis with osteomyelitis (BCO) lameness is a leg disorder in broilers leading to huge economic losses, food safety concerns, and animal welfare issues in the poultry industry. The active metabolite of vitamin D₃, 1,25-dihydroxyvitamin D₃, plays pivotal roles in mineral homeostasis, bone health, and immune systems which are essential for protection against BCO. Thus, we hypothesized that supplementation with a Solanum glaucophyllum-derived source of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃-glycosides) would be an effective measure to control lameness. Here, we report the optimum concentration of 1,25(OH)₂D₃-glycosides …

Elemental Content And Safety Evaluation Of Wild-Harvested Australian Abalone (Haliotis Spp.) Viscera: Addressing Safety Concerns In Food Waste Upcycling, Wing H. Chung, Liezhou Zhong, Ryu Takechi, Ranil Coorey, Janet Howieson

Research outputs 2022 to 2026

Abalone viscera has been shown to be a valuable human nutraceutical, yet the food safety considerations of consuming whole abalone viscera have been largely overlooked. Hence, this research was conducted to investigate and evaluate elemental compositions and safety of it. The elemental data was compared to international food safety regulations and evaluated using the USEPA hazard index (HI) equation and HI-derived estimated upper limit (EDUL) equation, which EDUL allows comparison of novel foods with a large variety of similar existing products. To further demonstrate that food safety of upcycled food could be improved with simple processing, a risk mitigation trial …

Lessons Learnt From Broad-Spectrum Coronavirus Antiviral Drug Discovery, Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Introduction: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.

Areas covered: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and …

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can A Rare Tumor Registry Accurately Represent The Real-World Patient Population?, Thomas Szabo Yamashita, Sophia M Williams-Perez, Sara Ehsan, Michelle Mulder, Daniel Kronenfeld, Chiang-Yu Huang, Hui Zhao, Kelly Merriman, Susan K Peterson, Mimi I Hu, Mark Zafereo, Julie Ann Sosa, Elizabeth G Grubbs

Faculty, Staff and Student Publications

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries.

Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer …

Early And Enduring: Targeting The Endothelium For Blood-Brain Barrier Protection, Silin Wu, Xuefang Sophie Ren, Yejie Shi

Faculty, Staff and Student Publications

The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.

Differentiation Activates Mitochondrial Opa1 Processing In Myoblast Cell Lines, Harpreet Kaur, Omar Carrillo, Iraselia Garcia, Isaiah Ramos, Shaynah St. Vallier, Patrick De La Torre, Alma Lopez, Megan Keniry, Daniela Bazan, Jorge Elizondo, Robert Gilkerson

School of Integrative Biological & Chemical Sciences Faculty Publications

Mitochondrial optic atrophy-1 (OPA1) plays key roles in adapting mitochondrial structure to bioenergetic function. When transmembrane potential across the inner membrane (Δψm) is intact, long (L-OPA1) isoforms shape the inner membrane through membrane fusion and the formation of cristal junctions. When Δψm is lost, however, OPA1 is cleaved to short, inactive S-OPA1 isoforms by the OMA1 metalloprotease, disrupting mitochondrial structure and priming cellular stress responses such as apoptosis. Previously, we demonstrated that L-OPA1 of H9c2 cardiomyoblasts is insensitive to loss of Δψm via challenge with the protonophore carbonyl cyanide chlorophenyl hydrazone (CCCP), but that CCCP-induced OPA1 processing is activated upon …

Strategies For The Development Of Metalloimmunotherapies, Xiaoqi Sun, Xingwu Zhou, Xiaoyue Shi, Omar A Abed, Xinran An, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies. By examining how metal ions modulate the innate and adaptive immune systems, as well as host-microbiota interactions, we discuss strategies for the development of such metalloimmunotherapies for the treatment of cancer and other immune-related diseases.

Radiation Therapy Quality Assurance Analysis Of Alliance A021501: Preoperative Mfolfirinox Or Mfolfirinox Plus Hypofractionated Radiation Therapy For Borderline Resectable Adenocarcinoma Of The Pancreas, Leila T Tchelebi, Diana Segovia, Koren Smith, Qian Shi, T J Fitzgerald, Michael D Chuong, Tyler J Zemla, Eileen M O'Reilly, Jeffrey A Meyerhardt, Eugene J Koay, Jessica Lowenstein, Ardaman Shergill, Matthew H G Katz, Joseph M Herman

Faculty, Staff and Student Publications

Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

Methods and materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable …

Eosinophilia During Lenalidomide Therapy In Myelodysplastic Syndrome, Koji Sasaki, Hagop Kantarjian, Guillermo Montalban-Bravo, Danielle Hammond, Elias Jabbour, Rashmi Kanagal-Shamanna, Kelly Chien, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Background: Lenalidomide is an immunomodulatory therapy used to treat multiple hematologic malignancies. The incidence of eosinophilia and hypereosinophilia during lenalidomide therapy, and the requirement for high-dose steroids are not well-defined PATIENTS AND METHODS: We retrospectively reviewed 44 patients with myelodysplastic syndromes who were treated with lenalidomide therapy from August 2006 and March 2023.

Results: Eosinophilia (0.5-1.5 × 109/L) and hypereosinophilia (>1.5 × 109/L) were observed in 6 patients (14%) and 4 patients (9%), respectively. The median duration of lenalidomide therapy was 6.5 months. Backward multivariate ordinary logistic regression identified higher absolute eosinophil count (OR, 4759.986; 95% CI, 11.223-2018772.073; P …

Vascular Heterogeneity Of Tight Junction Claudins Guides Organotropic Metastasis, Xunian Zhou, Valerie S Lebleu, Eliot Fletcher-Sananikone, Jiha Kim, Jianli Dai, Bingrui Li, Chia-Chin Wu, Hikaru Sugimoto, Toru Miyake, Lisa M Becker, Olga V Volpert, Erica Lawson, Cristina Espinosa Da Silva, Sarah I Patel, Akane Kizu, Ehsan A Ehsanipour, Di Sha, Jose Antonio Karam, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking …

Increasing Power In Phase Iii Oncology Trials With Multivariable Regression: An Empirical Assessment Of 535 Primary End Point Analyses, Alexander D Sherry, Adina H Passy, Zachary R Mccaw, Joseph Abi Jaoude, Timothy A Lin, Ramez Kouzy, Avital M Miller, Gabrielle S Kupferman, Esther J Beck, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: A previous study demonstrated that power against the (unobserved) true effect for the primary end point (PEP) of most phase III oncology trials is low, suggesting an increased risk of false-negative findings in the field of late-phase oncology. Fitting models with prognostic covariates is a potential solution to improve power; however, the extent to which trials leverage this approach, and its impact on trial interpretation at scale, is unknown. To that end, we hypothesized that phase III trials using multivariable PEP analyses are more likely to demonstrate superiority versus trials with univariable analyses.

Methods: PEP analyses were reviewed from …

Psychological Distress And Mental Health Care Utilization Among Black Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Aryce Battle, Andrea C Betts, John M Salsman, Joel Milam, Clark R Andersen, Kimberly A Miller, Susan K Peterson, Qian Lu, Christabel K Cheung, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

Background: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population.

Methods: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate …

Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann

Faculty, Staff and Student Publications

Combination approaches are needed to strengthen and extend the clinical response to KRAS

Clinical Outcomes And Healthcare Resource Utilization For Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents, Guillermo Garcia-Manero, Rayna K Matsuno, Ali Mcbride, Hina Mohammed, Danny Idryo, Ronda Broome, Autumn Herriman, Tiffany Johnson, Kristiana Wilkinson, Andrew Schrag, Colden Johanson, Monika Izano, Adeola Makinde, Sudipto Mukherjee

Faculty, Staff and Student Publications

Introduction: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States.

Patients and methods: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary …

Clonal Evolution Of Pancreatobiliary Neoplasms, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Feasibility And Acceptability Of A Nurse-Led Telehealth Intervention (Bolster) To Support Patients With Peritoneal Carcinomatosis And Their Caregivers: A Pilot Randomized Clinical Trial, Rachel A Pozzar, Andrea C Enzinger, Catherine Howard, Anna Tavormina, Ursula A Matulonis, Susana Campos, Joyce F Liu, Neil Horowitz, Panagiotis A Konstantinopoulos, Carolyn Krasner, Jaclyn A Wall, Kate Sciacca, Larissa A Meyer, Charlotta Lindvall, Alexi A Wright

Faculty, Staff and Student Publications

Objective: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP).

Methods: Pilot feasibility RCT. Recently hospitalized adults with advanced …

Neoadjuvant Talazoparib In Patients With Germline Brca1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Exploration Of Tumor Brca Mutational Status, Melinda L Telli, Jennifer K Litton, J Thaddeus Beck, Jason M Jones, Jay Andersen, Lida A Mina, Raymond Brig, Michael Danso, Yuan Yuan, William F Symmans, Julia F Hopkins, Lee A Albacker, Antonello Abbattista, Kay Noonan, Marielena Mata, A Douglas Laird, Joanne L Blum

Faculty, Staff and Student Publications

BACKGROUND: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study.

METHODS: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOne

RESULTS: All patients enrolled (N = 61) had TNBC. In the biomarker analysis population, 75.0% (39/52) and 25.0% (13/52) of patients exhibited BRCA1 and BRCA2 mutations, respectively. Strong concordance (97.8%) was observed between tumor BRCA and germline BRCA mutations, and 90.5% (38/42) of patients with …

Smyd5 Is A Ribosomal Methyltransferase That Catalyzes Rpl40 Lysine Methylation To Enhance Translation Output And Promote Hepatocellular Carcinoma, Bisi Miao, Ling Ge, Chenxi He, Xinghao Wang, Jibo Wu, Xiang Li, Kun Chen, Jinkai Wan, Shenghui Xing, Lingnan Ren, Zhennan Shi, Shengnan Liu, Yajun Hu, Jiajia Chen, Yanyan Yu, Lijian Feng, Natasha M Flores, Zhihui Liang, Xinyi Xu, Ruoxin Wang, Jian Zhou, Jia Fan, Bin Xiang, En Li, Yuanhui Mao, Jingdong Cheng, Kehao Zhao, Pawel K Mazur, Jiabin Cai, Fei Lan

Faculty, Staff and Student Publications

While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center, was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robust in vitro activity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W Clemens, Terence M Myckatyn, Arianna Di Napoli, Andrew L Feldman, Elaine S Jaffe, Cara L Haymaker, Steven M Horwitz, Kelly K Hunt, Marshall E Kadin, Colleen M Mccarthy, Roberto N Miranda, H Miles Prince, Fabio Santanelli Di Pompeo, Sari D Holmes, Linda G Phillips

Faculty, Staff and Student Publications

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

Determinant Of 30-Day Mortality Of Pulmonary Legionellosis: Do Coinfections Matter?, Takahiro Matsuo, Sebastian Wurster, Ying Jiang, Jeffrey Tarrand, Scott E Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

We retrospectively reviewed 64 cases of cancer with pulmonary legionellosis (Legionella pneumophila in 73%). Nearly all patients received Legionella-active antibiotics, yet 30-day mortality was 23%. Independent predictors of 30-day mortality were hyponatremia, bilateral lung involvement, and Sequential Organ Failure Assessment score ≥5. Lung coinfections were common (31%) but did not significantly increase mortality.