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Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain By Activation Of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 In The Dorsal Root Ganglia, Hee Kee Kim, Qi Wang, Seon-Hee Hwang, Patrick M Dougherty, Jing Wang, Salahadin Abdi

Faculty, Staff and Student Publications

Background: Many chemotherapeutic drugs, including paclitaxel, produce neuropathic pain in patients with cancer, which is a dose-dependent adverse effect. Such chemotherapy-induced neuropathic pain (CINP) is difficult to treat with existing drugs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidative responses and activates phosphorylated Nrf2 (pNrf2). We determined the analgesic effects of bardoxolone methyl (BM), an Nrf2 activator, and the role of pNrf2 on CINP.

Methods: CINP was induced in rats by intraperitoneally injecting paclitaxel on 4 alternate days in rats. BM was injected systemically as single or repeated injections after pain fully developed. RNA transcriptome, …

Imaging Predictors Of 4q12 Amplified And Rb1 Mutated Glioblastoma Idh-Wildtype, Antonio Dono, Jose Torres, Luis Nunez, Octavio Arevalo, Juan Carlos Rodriguez-Quinteros, Roy F Riascos, Arash Kamali, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Introduction: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma.

Methods: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group

Faculty, Staff and Student Publications

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a …

Cancer Patients With Clonal Hematopoiesis Die From Primary Malignancy Or Comorbidities Despite Higher Rates Of Transformation To Myeloid Neoplasms, Kelly S Chien, Faustine Ong, Kunhwa Kim, Ziyi Li, Rashmi Kanagal-Shamanna, Courtney D Dinardo, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Koji Sasaki, Sherry A Pierce, Hagop M Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

BACKGROUND: The occurrence of somatic mutations in patients with no evidence of hematological disorders is called clonal hematopoiesis (CH). CH, whose subtypes include CH of indeterminate potential and clonal cytopenia of undetermined significance, has been associated with both hematologic cancers and systemic comorbidities. However, CH's effect on patients, especially those with concomitant malignancies, is not fully understood.

METHODS: We performed a retrospective evaluation of all patients with CH at a tertiary cancer center. Patient characteristics, mutational data, and outcomes were collected and analyzed.

RESULTS: Of 78 individuals included, 59 (76%) had a history of cancer and 60 (77%) had moderate …

Visuo-Frontal Interactions During Social Learning In Freely Moving Macaques, Melissa Franch, Sudha Yellapantula, Arun Parajuli, Natasha Kharas, Anthony Wright, Behnaam Aazhang, Valentin Dragoi

Faculty, Staff and Student Publications

Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by …

Global Trend In Exosome Isolation And Application: An Update Concept In Management Of Diseases, Mohammadhassan Omrani, Hanieh Beyrampour-Basmenj, Rana Jahanban-Esfahlan, Mahnaz Talebi, Mortaza Raeisi, Zeinab Aliyari Serej, Naeimeh Akbar-Gharalari, Sina Khodakarimi, Jiaqian Wu, Abbas Ebrahimi-Kalan

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, …

A Generalized Calibrated Bayesian Hierarchical Modeling Approach To Basket Trials With Multiple Endpoints, Xiaohan Chi, Ying Yuan, Zhangsheng Yu, Ruitao Lin

Faculty, Staff and Student Publications

A basket trial simultaneously evaluates a treatment in multiple cancer subtypes, offering an effective way to accelerate the drug development in multiple indications. Many basket trials are designed and monitored based on a single efficacy endpoint, primarily the tumor response. For molecular targeted or immunotherapy agents, however, a single efficacy endpoint cannot adequately characterize the treatment effect. It is increasingly important to use more complex endpoints to comprehensively assess the risk–benefit profile of such targeted therapies. We extend the calibrated Bayesian hierarchical modeling approach (Chu and Yuan, 2018a) to monitor phase II basket trials with multiple endpoints. We …

Comparing 90-Day Postoperative Mortality After Neoadjuvant Proton-Based Versus Photon-Based Chemoradiotherapy For Esophageal Cancer, Pim J J Damen, Peter S N Van Rossum, Yiqing Chen, Chike O Abana, Zhongxing Liao, Brian P Hobbs, Radhe Mohan, Mariela Blum-Murphy, Wayne L Hofstetter, Steven H Lin

Faculty, Staff and Student Publications

PURPOSE: Evidence suggests that proton-beam therapy (PBT) results in less toxicity and postoperative complications compared to photon-based radiotherapy in patients who receive chemoradiotherapy followed by esophagectomy for cancer. Ninety-day mortality (90DM) is an important measure of the postoperative (nononcologic) outcome as proxy of quality-of-care. We hypothesize that PBT could reduce 90DM compared to photon-based radiotherapy.

MATERIALS AND METHODS: From a single-center retrospective database patients treated with chemoradiotherapy before esophagectomy for cancer were selected (1998-2022). Univariable logistic regression was used to study the association of radiotherapy modality with 90DM. Three separate methods were applied to adjust for confounding bias, including multivariable …

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy, Chike O Abana, Pim J Damen, Peter S Van Rossum, Pablo Lopez Bravo, Xiong Wei, Julianne M Pollard-Larkin, Paige L Nitsch, Mariela Blum Murphy, Wayne L Hofstetter, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

PURPOSE: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment.

PATIENTS AND METHODS: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were …

Analysis Of East Asia Subgroup In Study 309/Keynote-775: Lenvatinib Plus Pembrolizumab Versus Treatment Of Physician's Choice Chemotherapy In Patients With Previously Treated Advanced Or Recurrent Endometrial Cancer, Kan Yonemori, Keiichi Fujiwara, Kosei Hasegawa, Mayu Yunokawa, Kimio Ushijima, Shiro Suzuki, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Jae-Weon Kim, Byoung-Gie Kim, Peng-Hui Wang, Ting-Chang Chang, Keiko Yamamoto, Shirong Han, Jodi Mckenzie, Robert J Orlowski, Takuma Miura, Vicky Makker, Yong Man Kim

Faculty, Staff and Student Publications

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.

METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once …

The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett

Faculty, Staff and Student Publications

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence

Watching The Fall Of Roe V Wade: Media Exposure Relates To Us Women's Alcohol Use Intentions, Stacy M Post, Mary C Jobe, Arianne N Malekzadeh, Katarina E Aubuchon, Rebecca K Hoffman, Michelle L Stock, Lisa Bowleg

Faculty, Staff and Student Publications

OBJECTIVE: The Supreme Court of the United States’ decision in Dobbs v. Jackson Women’s Health Organization in June 2022 overturned Roe v. Wade and ended federal protection of abortion rights. Given the drastic policy changes as a result of the ruling and high exposure to media related to abortion, women opposed to the decision may have experienced distress, which could trigger maladaptive coping strategies, such as alcohol use. The present research examined how consuming abortion-related media in the weeks following the Dobbs decision impacted alcohol use intentions among women of reproductive age residing in the 13 “trigger law” states that …

Artificial Intelligence-Based Radiotherapy Contouring And Planning To Improve Global Access To Cancer Care, Laurence E Court, Ajay Aggarwal, Anuja Jhingran, Komeela Naidoo, Tucker Netherton, Adenike Olanrewaju, Christine Peterson, Jeannette Parkes, Hannah Simonds, Christoph Trauernicht, Lifei Zhang, Beth M Beadle, Radiation Planning Assistant Consortium Collaborators, Affiliations Expand

Faculty, Staff and Student Publications

PURPOSE: Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.

METHODS: The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.

RESULTS: For cervical cancer, RPA plans using bony landmarks were scored as …

Trps1 Expression In Non-Melanocytic Cutaneous Neoplasms: An Immunohistochemical Analysis Of 200 Cases, Yi A Liu, Phyu P Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Qingqing Ding, Woo Cheal Cho

Faculty, Staff and Student Publications

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A Shepherd, Marie Florescu, Parneet Cheema, Quincy S C Chu, Sang-We Kim, Daniel Morgensztern, Melissa L Johnson, Sophie Cousin, Dong-Wan Kim, Mor T Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J Ambrose, Sajan Khosla, Avinash Reddy, Deanna L Russell, Mohamed Reda Keddar, James P Conway, J Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J Jewsbury, Sonia Iyer, Simon T Barry, Jan Cosaert, John V Heymach

Faculty, Staff and Student Publications

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure …

Amyopathic Dermatomyositis May Be On The Spectrum Of Autoinflammatory Disease: A Clinical Review, Saika Sharmeen, Lisa Christopher-Stine, Joann N Salvemini, Peter Gorevic, Richard Clark, Qingping Yao

Faculty, Staff and Student Publications

Systemic autoinflammatory diseases (SAIDs) are distinct from autoimmune diseases. The former primarily results from abnormal innate immune response and genetic testing is crucial for disease diagnosis. Similar cutaneous involvement is a main feature for both SAID and dermatomyositis (DM), so they can be confused with each other. A literature search of PubMed and MEDLINE was conducted for relevant articles. The similarities and differences between these two types of diseases were analyzed. We found phenotypic similarities between these two types of disorders. Accumulating data supports a major role of the innate immune system and a similar cytokine profile. Molecular testing using …

Spectrophotometric Analysis Of Purple Urine Secondary To Methylene Blue And Hydroxocobalamin Co-Administration, Jeremy Hardin, Henrik Galust, Richard Franklin Clark, Binh Ly, Raymond Theodore Suhandynata

Faculty, Staff and Student Publications

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week.

METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. …

Systematic Evaluation Of Mri-Based Characterization Of Tumor-Associated Vascular Morphology And Hemodynamics Via A Dynamic Digital Phantom, Chengyue Wu, David A Hormuth, Ty Easley, Federico Pineda, Gregory S Karczmar, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose: Validation of quantitative imaging biomarkers is a challenging task, due to the difficulty in measuring the ground truth of the target biological process. A digital phantom-based framework is established to systematically validate the quantitative characterization of tumor-associated vascular morphology and hemodynamics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Approach: A digital phantom is employed to provide a ground-truth vascular system within which 45 synthetic tumors are simulated. Morphological analysis is performed on high-spatial resolution DCE-MRI data (spatial/temporal resolution = 30 to 300μm/60s" role="presentation" style="box-sizing: inherit; display: inline-block; line-height: 0; font-size: 18.08px; font-size-adjust: none; overflow-wrap: normal; word-spacing: normal; text-wrap-mode: …

Prenatal Vs Postnatal Diagnosis Of 22q112 Deletion Syndrome: Cardiac And Noncardiac Outcomes Through 1 Year Of Age, Lindsay R Freud, Stephanie Galloway, T Blaine Crowley, Julie Moldenhauer, Ann Swillen, Jeroen Breckpot, Antoni Borrell, Neeta L Vora, Bettina Cuneo, Hilary Hoffman, Lisa Gilbert, Beata Nowakowska, Maciej Geremek, Anna Kutkowska-Kaźmierczak, Joris R Vermeesch, Koen Devriendt, Tiffany Busa, Sabine Sigaudy, Trisha Vigneswaran, John M Simpson, Jeffrey Dungan, Nina Gotteiner, Karl-Philipp Gloning, Maria Cristina Digilio, Marta Unolt, Carolina Putotto, Bruno Marino, Gabriela Repetto, Magdalena Fadic, Sixto Garcia-Minaur, Ana Achón Buil, Mary Ann Thomas, Deborah Fruitman, Taylor Beecroft, Pui Wah Hui, Solveig Oskarsdottir, Rachael Bradshaw, Amanda Criebaum, Mary E Norton, Tiffany Lee, Miwa Geiger, Leslie Dunnington, Jacqueline Isaac, Louise Wilkins-Haug, Lindsey Hunter, Claudia Izzi, Marika Toscano, Tullio Ghi, Julie Mcglynn, Francesca Romana Grati, Beverly S Emanuel, Kimberly Gaiser, J William Gaynor, Elizabeth Goldmuntz, Daniel E Mcginn, Erica Schindewolf, Oanh Tran, Elaine H Zackai, Qi Yan, Anne S Bassett, Ronald Wapner, Donna M Mcdonald-Mcginn

Faculty, Staff and Student Publications

Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis.

Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome.

Study design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Clinical And Dosimetric Results Of Proton Or Photon Radiation Therapy For Large (>5 Cm) Hepatocellular Carcinoma: A Retrospective Analysis, Rodney Cheng-En Hsieh, Ching-Hsin Lee, Hsiao-Chieh Huang, Shu-Wei Wu, Chen-Yu Chou, Sheng-Ping Hung, Chao-Wei Lee, Sunil Krishnan, Bhanu Prasad Venkatesulu, Jin-Chiao Lee, Yung-Chih Chou, Kun-Ming Chan, Po-Ting Lin, Wei-Chen Lee, Chen-Chun Lin, Shen-Yen Lin, Ji-Hong Hong

Faculty, Staff and Student Publications

Purpose: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy.

Methods and materials: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison.

Results: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 …

Stroke And The Microbiome, Anik Banerjee, Swati Mohapatra, Louise D Mccullough

Faculty, Staff and Student Publications

No abstract provided.

Empirically Derived Principles For Research Funding Success: A Primer For Early Career Academic Investigators, Kareem A Wahid, Michael K Rooney, Jillian R Gunther, Amy C Moreno, Chelsea C Pinnix, Charles R Thomas, Clifton D Fuller

Faculty, Staff and Student Publications

No abstract provided.

Efficient Gene Editing For Heart Disease Via Elip-Based Crispr Delivery System, Xing Yin, Romain Harmancey, Brion Frierson, Jean G Wu, Melanie R Moody, David D Mcpherson, Shao-Ling Huang

Faculty, Staff and Student Publications

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in …

Indigenous Approaches To Health Assessment: A Scoping Review Protocol, Nabina Sharma, Jennifer D Walker, Elizabeth Wenghofer, Taima Moeke-Pickering, Jeannette Lindenbach

Faculty, Staff and Student Publications

BACKGROUND: Health assessment tools developed using mainstream or Western concepts have been widely used in clinical practice worldwide. However, even culturally adapted or culturally based tools may not be relevant in other social contexts if they are grounded in Western beliefs and perspectives. The application of mainstream assessment tools, when used in Indigenous populations, can lead to the inappropriate application of normative data and inaccurate or biased diagnosis of conditions as Indigenous concepts of health differ from Western biomedical concepts of health. Thus, considering the need for culturally meaningful, sensitive, safe, and unbiased health assessment approaches and instruments over recent …

Pan-Cancer Proteogenomics Characterization Of Tumor Immunity, Francesca Petralia, Weiping Ma, Tomer M Yaron, Francesca Pia Caruso, Nicole Tignor, Joshua M Wang, Daniel Charytonowicz, Jared L Johnson, Emily M Huntsman, Giacomo B Marino, Anna Calinawan, John Erol Evangelista, Myvizhi Esai Selvan, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Xiaoyu Song, Berk Turhan, Karen E Christianson, David A Lewis, Eden Z Deng, Daniel J B Clarke, Jeffrey R Whiteaker, Jacob J Kennedy, Lei Zhao, Rossana Lazcano Segura, Harsh Batra, Maria Gabriela Raso, Edwin Roger Parra, Rama Soundararajan, Ximing Tang, Yize Li, Xinpei Yi, Shankha Satpathy, Ying Wang, Maciej Wiznerowicz, Tania J González-Robles, Antonio Iavarone, Sara J C Gosline, Boris Reva, Ana I Robles, Alexey I Nesvizhskii, D R Mani, Michael A Gillette, Robert J Klein, Marcin Cieslik, Bing Zhang, Amanda G Paulovich, Robert Sebra, Zeynep H Gümüş, Galen Hostetter, David Fenyö, Gilbert S Omenn, Lewis C Cantley, Avi Ma'ayan, Alexander J Lazar, Michele Ceccarelli, Pei Wang, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%-20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents.

The Emerging Importance Of Skull-Brain Interactions In Traumatic Brain Injury, Peixi Zhao, Rui Jin, Bin Zhao, Le Han, Wenjuan Chen, Nina Hao, Yi Cui, Ankit Madan, Joy Awosika, Shane Lloyd, Yili Zhang

Faculty, Staff and Student Publications

Background and Objective

Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer.

Methods

The literature on ICI treatment in GI cancers was searched in the …

Mechanisms Of Sleep Disturbances In Long-Term Cancer Survivors: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Huiqi Wang, Tara M Brinkman, Kathy Ruble, Eric S Zhou, Oxana Palesh, Robyn Stremler, Rebecca Howell, Daniel A Mulrooney, Valerie M Crabtree, Sogol Mostoufi-Moab, Kevin Oeffinger, Joseph Neglia, Yutaka Yasui, Gregory T Armstrong, Kevin Krull

Faculty, Staff and Student Publications

Background: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates.

Methods: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep …

Multiple Control Of Azoquinoline Based Molecular Photoswitches, Youming Lv, Hebo Ye, Lei You

Faculty, Staff and Student Publications

Multi-addressable molecular switches with high sophistication are creating intensive interest, but are challenging to control. Herein, we incorporated ring-chain dynamic covalent sites into azoquinoline scaffolds for the construction of multi-responsive and multi-state switching systems. The manipulation of ring-chain equilibrium by acid/base and dynamic covalent reactions with primary/secondary amines allowed the regulation of