Medicine and Health Sciences Commons^™

Editorial: Expert Opinions In Neurocognitive Aging And Behavior: Neural Rehabilitation For Elder People, Ping Zhou, Yingchun Zhang, Sheng Li

Faculty, Staff and Student Publications

No abstract provided.

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

Faculty, Staff and Student Publications

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Clinical Outcomes: Endoscopic Resection Of Duodenal Ampullary Lesions, Stephanie M Woo, Mark J Real, Brett M Will, Eric J Kim, Jiling Chou, Ahmed A Alsaiari, Ahmad Nakshabandi, Walid M Chalhoub, Nadim G Haddad

Faculty, Staff and Student Publications

Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews. The objective of this study is to describe endoscopic papillectomy outcomes to further refine management guidelines.

Methods: This is a retrospective study of patients who underwent endoscopic papillectomy. Demographic data were included. Details regarding lesions and procedures were also collected, including endoscopic impression, size, resection method and adjunctive …

Easy Nanostring Ncounter Data Analysis With The Nanotube, Caleb A Class, Caiden J Lukan, Christopher A Bristow, Kim-Anh Do

Faculty, Staff and Student Publications

Summary: The NanoTube is an open-source pipeline that simplifies the processing, quality control, normalization and analysis of NanoString nCounter gene expression data. It is implemented in an extensible R library, which performs a variety of gene expression analysis techniques and contains additional functions for integration with other R libraries performing advanced NanoString analysis techniques. Additionally, the NanoTube web application is available as a simple tool for researchers without programming expertise.

Availability and implementation: The NanoTube R package is available on Bioconductor under the GPL-3 license (https://www.bioconductor.org/packages/NanoTube/). The R-Shiny application can be downloaded at https://github.com/calebclass/Shiny-NanoTube, or a simplified …

Survival Outcomes Used To Validate Version 9 Of The American Joint Committee On Cancer Staging System For Appendiceal Cancer, Lauren M Janczewski, Amanda E Browner, Joseph H Cotler, Heidi Nelson, Sanjay Kakar, Norman J Carr, Nader N Hanna, Andreana N Holowatyj, Richard M Goldberg, M Kay Washington, Elliot A Asare, Michael J Overman, American Joint Committee On Cancer Expert Panel On Cancers For The Lower Gastrointestinal Appendix Disease Site

Faculty, Staff and Student Publications

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 …

Treatment De-Escalation In Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia: The Emerging Role Of Chemotherapy-Free Regimens, Fadi G Haddad, Jacki Sawyers, Nicholas J Short

Faculty, Staff and Student Publications

The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many …

3,3′-Diindolylmethane Augments 5-Fluorouracil-Inducedgrowth Suppression In Gastric Cancer Cells Through Suppression Of The Akt/Gsk-3Β And Wnt/Beta-Catenin, Cong Shan Li, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Gastric cancer (GC) is one of the most lethal cancers in South Korea, and it is a cancer of concern worldwide. 5-fluorouracil (5-Fu) is commonly used as the first-line therapy for advanced GC; however, its side effects often limit the dosage range and impair patients' quality of life. Due to the limitations of current chemotherapy, new anticancer therapies are urgently needed. 3,3'-diindolylmethane (DIM) has been reported to have the ability to protect against various types of cancer. Our study aimed to elucidate the anticancer effect of DIM in GC when treated with the chemotherapeutic agent 5-Fu. In our results, combined …

Hras Mutations Define A Distinct Subgroup In Head And Neck Squamous Cell Carcinoma, Niamh Coleman, Kathrina L Marcelo, Julia F Hopkins, Nusrat Israr Khan, Robyn Du, Lingzhi Hong, Edward Park, Binaifer Balsara, Mollie Leoni, Curtis Pickering, Jeffrey Myers, John Heymach, Lee A Albacker, David Hong, Maura Gillison, Xiuning Le

Faculty, Staff and Student Publications

Purpose: In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population.

Methods: We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method).

Results: Two hundred forty-nine patients with HRAS-mutant HNSCC were identified …

Pilot Study Of A Spanish Language Measure Of Financial Toxicity In Underserved Hispanic Cancer Patients With Low English Proficiency, Julia J Shi, Gwendolyn J Mcginnis, Susan K Peterson, Nicolette Taku, Ying-Shiuan Chen, Robert K Yu, Chi-Fang Wu, Tito R Mendoza, Sanjay S Shete, Hilary Ma, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Diem-Khanh Nguyen, Kelsey W Kaiser, Grace L Smith

Faculty, Staff and Student Publications

BACKGROUND: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population.

METHODS: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish,

RESULTS: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the …

Genome-Wide Characterization Of Trichome Birefringence-Like Genes Provides Insights Into Fiber Yield Improvement, Ziyin Li, Yuzhen Shi, Xianghui Xiao, Jikun Song, Pengtao Li, Juwu Gong, Haibo Zhang, Wankui Gong, Aiying Liu, Renhai Peng, Haihong Shang, Qun Ge, Junwen Li, Jingtao Pan, Quanjia Chen, Quanwei Lu, Youlu Yuan

Faculty, Staff and Student Publications

Cotton is an important fiber crop. The cotton fiber is an extremely long trichome that develops from the epidermis of an ovule. The trichome is a general and multi-function plant organ, and trichome birefringence-like (TBL) genes are related to trichome development. At the genome-wide scale, we identified TBLs in four cotton species, comprising two cultivated tetraploids (Gossypium hirsutum and G. barbadense) and two ancestral diploids (G. arboreum and G. raimondii). Phylogenetic analysis showed that the TBL genes clustered into six groups. We focused on GH_D02G1759 in group IV because it was located in a …

Exosomal Lipid Biomarkers Of Oligodendrocyte Pathology To Predict Scoliosis In Children With Cerebral Palsy, Nune Darbinian, Emily C Sparks, Armine Darbinyan, Nana Merabova, Tamara Tatevosian-Geller, Katie Calaku, Sarah Bachman, Huaqing Zhao, Shohreh Amini, Laura Goetzl, Solomon P Samuel, Amer Samdani, Michael E Selzer

Faculty, Staff and Student Publications

INTRODUCTION: Cerebral Palsy (CP), the most common cause of disability in children, is phenotypically heterogeneous. Approximately 20% of cases develop severe scoliosis. A pathological hallmark of CP is periventricular leukomalacia (PVL), which is due to dysmyelination, suggesting the possibility of a lipidomic abnormality. Risk factors for CP include perinatal hypoxia, prematurity, multiple gestation, ischemia, infection, and maternal alcohol consumption. There is evidence for low serum levels of omega-3 (ω-3) fatty acids in CP patients, and separately in idiopathic scoliosis. Many effects of free fatty acids (FFAs) are mediated via specific G protein-coupled free fatty acid receptors (FFARs), which play essential …

Maternal Blood Lipid Biomarkers Of Oligodendrocyte Pathology To Predict Fetal Alcohol Spectrum Disorders, Nune Darbinian, Emily C Sparks, Armine Darbinyan, Nana Merabova, Gabriel Tatevosian, Ekaterina Vadachkoria, Huaqing Zhao, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

INTRODUCTION: Up to 9.9% of children have fetal alcohol spectrum disorders (FASD), the most frequent cause of intellectual disability in the US. FASD may involve abnormal brain development, including dysmyelination, suggesting abnormal development of oligodendrocytes (OLs), which make myelin and are rich in lipids. Indeed, low serum levels of omega-3 fatty acids (ω-3) have been reported in FASD. Free fatty acids bind to specific receptors (FFARs). We have isolated cell type-specific fetal brain-derived exosomes (FB-E) from maternal blood and sampled their contents to search for lipid-related biomarkers that predict FASD.

METHODS: Blood samples were collected from two groups of pregnant …

Bayesian Single-To-Double Arm Transition Design Using Both Short-Term And Long-Term Endpoints, Tianlin Xu, Haolun Shi, Ruitao Lin

Faculty, Staff and Student Publications

The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials. Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. …

Evolutionary History Of Transformation From Chronic Lymphocytic Leukemia To Richter Syndrome, Erin M Parry, Ignaty Leshchiner, Romain Guièze, Connor Johnson, Eugen Tausch, Sameer A Parikh, Camilla Lemvigh, Julien Broséus, Sébastien Hergalant, Conor Messer, Filippo Utro, Chaya Levovitz, Kahn Rhrissorrakrai, Liang Li, Daniel Rosebrock, Shanye Yin, Stephanie Deng, Kara Slowik, Raquel Jacobs, Teddy Huang, Shuqiang Li, Geoff Fell, Robert Redd, Ziao Lin, Binyamin A Knisbacher, Dimitri Livitz, Christof Schneider, Neil Ruthen, Liudmila Elagina, Amaro Taylor-Weiner, Bria Persaud, Aina Martinez, Stacey M Fernandes, Noelia Purroy, Annabelle J Anandappa, Jialin Ma, Julian Hess, Laura Z Rassenti, Thomas J Kipps, Nitin Jain, William Wierda, Florence Cymbalista, Pierre Feugier, Neil E Kay, Kenneth J Livak, Brian P Danysh, Chip Stewart, Donna Neuberg, Matthew S Davids, Jennifer R Brown, Laxmi Parida, Stephan Stilgenbauer, Gad Getz, Catherine J Wu

Faculty, Staff and Student Publications

Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. …

Risk Stratification Of Postoperative Cardiopulmonary Toxicity After Trimodality Therapy For Esophageal Cancer, Roman O Kowalchuk, Grant M Spears, Lindsay K Morris, Dawn Owen, Harry H Yoon, Krishan Jethwa, Michael D Chuong, Matthew J Ferris, Michael G Haddock, Christopher L Hallemeier, Dennis Wigle, Steven H Lin, Kenneth W Merrell

Faculty, Staff and Student Publications

Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.

Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used.

Results: From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and …

A Th2-Score In The Tumor Microenvironment As A Predictive Biomarker Of Response To Bacillus Calmette Guérin In Patients With Non-Muscle Invasive Bladder Carcinoma: A Retrospective Study, Gustavo Martín Villoldo, María Teresa Pombo, Mariana Aris, Joaquín Chemi, Pablo Mandó, Supriya Nagaraju, Juan Camean, Adrián Burioni, Deborah Egea, Mora Amat, José León Mellado, José Mordoh, Alberto Villaronga, María Marcela Barrio

Faculty, Staff and Student Publications

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ …

Adolescent Loneliness During The Covid-19 Pandemic: The Role Of Pre-Pandemic Risk Factors, Hena Thakur, Morgan Stutts, Jae Wan Choi, Jeff R Temple, Joseph R Cohen

Faculty, Staff and Student Publications

The COVID-19 pandemic is a global mental health crisis that disproportionately impacts adolescents. Loneliness is a particularly salient pandemic psychosocial outcome to understand; however, research to date on this outcome is sparse and largely cross-sectional. In response, we examined pre-pandemic risk factors for pandemic loneliness. Further, we examined how risk may differ based on key demographics, and whether mediation or moderation models best explained potential disparities in experiencing loneliness. Self-reported, pre-pandemic mental health, trauma exposure, and family conflict survey data were collected at Wave 1 in a diverse sample of 369 adolescents (54.5% female, 45.5% male; 30.1% White; 30.9% Black; …

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

Faculty, Staff and Student Publications

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …

Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M Holloman, Mary P Berg, Bronwyn Bryant, Lisa Ross Dixon, Melissa R George, Julie Katz Karp, Barbara Ec Knollmann-Ritschel, Victor Gerardo Prieto, Charles F Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B Mccloskey

Faculty, Staff and Student Publications

Medical student interest and pursuit of a career in pathology have been steadily declining since 2015. We conducted three separate surveys of medical students to better understand these trends. In our first survey, we focused on assessing U.S. allopathic medical students understanding and perceptions of pathology. We later surveyed U.S. osteopathic medical students as a companion to the allopathic medical student survey, in which many similarities were discovered with some key differences. In our final survey, we specifically looked at curriculum differences between the U.S. allopathic medical schools that graduate the most students who enter pathology training programs (Group 1) …

Spatial Heterogeneity Of T Cell Repertoire Across Nsclc Tumors, Tumor Edges, Adjacent And Distant Lung Tissues, Qikang Hu, Meredith L Frank, Yang Gao, Liyan Ji, Muyun Peng, Chen Chen, Bin Wang, Yan Hu, Zeyu Wu, Jina Li, Lu Shu, Qiongzhi He, Yingqian Zhang, Xuefeng Xia, Jianjun Zhang, Xin Yi, Alexandre Reuben, Fenglei Yu

Faculty, Staff and Student Publications

BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients.

METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed …

Are Trauma Surgeons Prepared? A Survey Of Trauma Surgeons’ Disaster Preparedness Before And During The Covid-19 Pandemic, Jay Doucet, David V Shatz, Lewis J Kaplan, Eileen M Bulger, Jeannette Capella, Deborah A Kuhls, Mary Fallat, Kyle N Remick, Christopher Newton, Adam Fox, Randeep Jawa, John A Harvin, David P Blake, Marko Bukur, Jonathan Gates, James Ficke, Mark L Gestring, The American Association For Surgery Of Trauma Disaster Committee

Faculty, Staff and Student Publications

OBJECTIVE: US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons' MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic's third year.

METHODS: Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, …

Translating Energy Balance Research From The Bench To The Clinic To The Community: Parallel Animal-Human Studies In Cancer, Miriam B Garcia, Keri L Schadler, Joya Chandra, Steven K Clinton, Kerry S Courneya, Zobeida Cruz-Monserrate, Carrie R Daniel, Andrew J Dannenberg, Wendy Demark-Wahnefried, Mark W Dewhirst, Carol J Fabian, Stephen D Hursting, Melinda L Irwin, Neil M Iyengar, Jennifer L Mcquade, Kathryn H Schmitz, Karen Basen-Engquist

Faculty, Staff and Student Publications

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer …

Strengthening Deep-Learning Models For Intracranial Hemorrhage Detection: Strongly Annotated Computed Tomography Images And Model Ensembles, Dong-Wan Kang, Gi-Hun Park, Wi-Sun Ryu, Dawid Schellingerhout, Museong Kim, Yong Soo Kim, Chan-Young Park, Keon-Joo Lee, Moon-Ku Han, Han-Gil Jeong, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance.

METHODS: We used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and …

Clinical Insights Into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, And Future Directions, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or …

Pre-Epithelialized Cryopreserved Tracheal Allograft For Neo-Trachea Flap Engineering, Ning Zeng, Youbai Chen, Yewen Wu, Mengqing Zang, Rene D Largo, Edward I Chang, Mark V Schaverien, Peirong Yu, Qixu Zhang

Faculty, Staff and Student Publications

Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection.

Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique …

Climate And Health: Impact Of Climate Education On Nursing Student Knowledge, Confidence, And Intent To Act, Beth Tremblay, Janice Hawkins

Ellmer School of Nursing Faculty Publications

Background: Because climate change negatively impacts human health, nurses need skills to mitigate climate change and nurse educators need effective educational strategies to teach climate change content in undergraduate nursing programs. To address this need, we embedded an energy efficiency treasure hunt and Climate for Health Ambassador Training into our prelicensure nursing curricula.

Purpose: To evaluate the impact of these educational activities on self-reported knowledge, confidence, and intent to engage in climate action.

Methods: A quasi-experimental one-group posttest design examined the effectiveness of 2 educational interventions on increasing knowledge, confidence, and intent to engage in climate action. A convenience sample …

Stem Cell Theory Of Cancer: Origin Of Metastasis And Sub-Clonality, Shi-Ming Tu, Cesar Moran, William Norton, Niki M Zacharias

Faculty, Staff and Student Publications

Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and …

Chd1, A Multifaceted Epigenetic Remodeler In Prostate Cancer, Haoyan Li, Loraine Gigi, Di Zhao

Faculty, Staff and Student Publications

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1's …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Targeting T Cell Checkpoints 41bb And Lag3 And Myeloid Cell Cxcr1/Cxcr2 Results In Antitumor Immunity And Durable Response In Pancreatic Cancer, Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y Maeda, John A Zebala, Denise J Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y Alan Wang, Nicholas E Navin, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is considered non-immunogenic, with trials showing its recalcitrance to PD1 and CTLA4 immune checkpoint therapies (ICTs). Here, we sought to systematically characterize the mechanisms underlying de novo ICT resistance and to identify effective therapeutic options for PDAC. We report that agonist 41BB and antagonist LAG3 ICT alone and in combination, increased survival and antitumor immunity, characterized by modulating T cell subsets with antitumor activity, increased T cell clonality and diversification, decreased immunosuppressive myeloid cells and increased antigen presentation/decreased immunosuppressive capability of myeloid cells. Translational analyses confirmed the expression of 41BB and LAG3 in human PDAC. Since …