Medical Sciences Commons^™

Multi-Institutional Study Of Pathologist Reading Of The Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay For Gastric Or Gastroesophageal Junction Cancer, Aileen I Fernandez, Charles J Robbins, Patricia Gaule, Diana Agostini-Vulaj, Robert A Anders, Andrew M Bellizzi, Wei Chen, Zongming Eric Chen, Purva Gopal, Lei Zhao, Mikhail Lisovsky, Xiuli Liu, Jinru Shia, Huamin Wang, Zhaohai Yang, Leena Mccann, Yvonne G Chan, Jodi Weidler, Michael Bates, Xuchen Zhang, David L Rimm

Faculty, Staff and Student Publications

The assessment of the expression of programmed cell death ligand-1 (PD-L1) using immunohistochemistry (IHC) has been controversial since its introduction. The methods of assessment and the range of assays and platforms contribute to confusion. Perhaps the most challenging aspect of PD-L1 IHC is the combined positive score (CPS) method of interpretation of IHC results. Although the CPS method is prescribed for more indications than any other PD-L1 scoring system, its reproducibility has never been rigorously assessed. In this study, we collected a series of 108 gastric or gastroesophageal junction cancer cases, stained them using the Food and Drug Administration-approved 22C3 …

Publisher Correction: Comprehensive Molecular Characterization Of Mitochondrial Genomes In Human Cancers, Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J Yoon, Yang Yang, Inigo Martincorena, Chad J Creighton, John N Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J Campbell, Han Liang, Pcawg Consortium

Faculty, Staff and Student Publications

No abstract provided.

Long Noncoding Rna 01534 Maintains Cancer Stemness By Downregulating Endoplasmic Reticulum Stress Response In Colorectal Cancer, Momoko Ichihara, Hidekazu Takahashi, Naohiro Nishida, Cristina Ivan, Daisuke Okuzaki, Yuhki Yokoyama, Masahisa Ohtsuka, Norikatsu Miyoshi, Mamoru Uemura, Shinji Tanaka, George Adrian Calin, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto

Faculty, Staff and Student Publications

Background: Studies have shown that cancer stemness and the endoplasmic reticulum (ER) stress response are inversely regulated in colorectal cancer (CRC), but the mechanism has not been fully clarified. Long noncoding RNAs (lncRNAs) play key roles in cancer progression and metastasis. In this study we investigated lncRNA 01534 (LINC01534) as a possible modulator between cancer stemness and ER stress response.

Methods: In vitro experiments using CRC cell lines were performed to explore a possible role of LINC01534. The expression of LINC01534 in clinical CRC samples was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization.

Results: Silencing …

Bayesess: A Tool For Quantifying The Impact Of Parametric Priors In Bayesian Analysis, Jaejoon Song, Satoshi Morita, Ying-Wei Kuo, J Jack Lee

Faculty, Staff and Student Publications

Bayesian inference has become an attractive choice for scientists seeking to incorporate prior knowledge into their modeling framework. While the R community has been an important contributor in facilitating Bayesian statistical analyses, software to evaluate the impact of prior knowledge to such modeling framework has been lacking. In this article, we present BayesESS, a comprehensive, free, and open source R package for quantifying the impact of parametric priors in Bayesian analysis. We also introduce an accompanying web-based application for estimating and visualizing Bayesian effective sample size for purposes of conducting or planning Bayesian analyses.

Unlocking The Promise Of Systemic Sting Agonist For Cancer Immunotherapy, Xiaoqi Sun, Xingwu Zhou, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Stimulator of interferon genes (STING) pathway is the key innate immune pathway involving in cancer immunity. Emerging new molecules and drug delivery systems have made systemic STING agonist immunotherapy possible and demonstrated efficient tumor eradication in preclinical studies. In this perspective, we will discuss the potential mechanisms of STING agonism as a multifaceted anti-cancer therapy and the pharmacological challenges associated with systemic delivery of STING agonists on the level of organs, tissues, cells, and intracellular compartments. We will present and discuss drug delivery strategies to address these challenges. New advances in the field can unlock the promise of systemic STING …

A Model For Gastrointestinal Tract Motility In A 4d Imaging Phantom Of Human Anatomy, Ergys Subashi, Paul Segars, Harini Veeraraghavan, Joseph Deasy, Neelam Tyagi

Faculty, Staff and Student Publications

BACKGROUND: Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms.

PURPOSE: To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy.

MATERIALS AND METHODS: Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on …

Combining Physics-Based Models With Deep Learning Image Synthesis And Uncertainty In Intraoperative Cone-Beam Ct Of The Brain, Xiaoxuan Zhang, Alejandro Sisniega, Wojciech B Zbijewski, Junghoon Lee, Craig K Jones, Pengwei Wu, Runze Han, Ali Uneri, Prasad Vagdargi, Patrick A Helm, Mark Luciano, William S Anderson, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention.

PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality.

METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network …

Cone-Beam Ct Sampling Incompleteness: Analytical And Empirical Studies Of Emerging Systems And Source-Detector Orbits, Pengwei Wu, Aina Tersol, Rolf Clackdoyle, John M Boone, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

PURPOSE: Motivated by emerging cone-beam computed tomography (CBCT) systems and scan orbits, we aim to quantitatively assess the completeness of data for 3D image reconstruction-in turn, related to "cone-beam artifacts." Fundamental principles of cone-beam sampling incompleteness are considered with respect to an analytical figure-of-merit [FOM, denoted

APPROACH:A previously proposed analytical FOM [tan ( ψmin ) , defined as the minimum angle between a point in the 3D image reconstruction and the x-ray source over the scan orbit] was analyzed for a variety of CBCT geometries. A physical test phantom was configured with parallel disk pairs (perpendicular to the z-axis) …

Nonlinear Propagation Of Quasiplanar Shear Wave Beams In Soft Elastic Media With Transverse Isotropy, John M Cormack, Mark F Hamilton

Faculty, Staff and Student Publications

Model equations are developed for shear wave propagation in a soft elastic material that include effects of nonlinearity, diffraction, and transverse isotropy. A theory for plane wave propagation by Cormack [J. Acoust. Soc. Am. 150, 2566 (2021)] is extended to include leading order effects of wavefront curvature by assuming that the motion is quasiplanar, which is consistent with other paraxial model equations in nonlinear acoustics. The material is modeled using a general expansion of the strain energy density to fourth order in strain that comprises thirteen terms defining the elastic moduli. Equations of motion for the transverse displacement components are …

Utilization Of Indoor Tanning: A Cross-Sectional Study Using Mobile Device Data, Mackenzie R Wehner, Yao Li, Ashna A Sethi, Candice L Hinkston, Nasim Khalfe, Carly F Stender, Malgorzata K Nowakowska, Olivia G Cohen, Sharon H Giordano, Eleni Linos

Faculty, Staff and Student Publications

No abstract provided.

Secondary Validation Of An Ovarian Cancer-Specific Comorbidity Index In A Us Population, Chelsey Vranes, Hui Zhao, Mette Calundann Noer, Shuangshuang Fu, Charlotte C Sun, Ross Harrison, Pedro T Ramirez, Claus Kim Høgdall, Sharon H Giordano, Larissa A Meyer

Faculty, Staff and Student Publications

Objectives: The Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population.

Methods: A cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall …

Current Treatment Strategies And Risk Stratification For Oral Carcinoma, Issa Mohamad, Mica D E Glaun, Kumar Prabhash, Ahmed Busheri, Stephen Y Lai, Vanita Noronha, Ali Hosni

Faculty, Staff and Student Publications

Management of oral cavity squamous cell carcinoma (OSCC) involves a multidisciplinary team approach. Surgery is ideally the primary treatment option for nonmetastatic OSCC, and less invasive curative surgical approaches are preferred in early-stage disease to minimize surgical-related morbidity. For patients at high risk of recurrence, adjuvant treatment using radiation therapy or chemoradiation is often used. Systemic therapy may also be used in the neoadjuvant setting (for advanced-stage disease with the intent of mandibular preservation) or in the palliative setting (for nonsalvageable locoregional recurrence and/or distant metastases). Patient involvement in treatment decision is the key for patient-driven management, particularly in clinical …

Vestigial-Like 1 (Vgll1): An Ancient Co-Transcriptional Activator Linking Wing, Placenta, And Tumor Development, Heather M Sonnemann, Barbara Pazdrak, Dinler A Antunes, Jason Roszik, Gregory Lizée

Faculty, Staff and Student Publications

Vestigial-like 1 (VGLL1) is a recently discovered driver of proliferation and invasion that is expressed in many aggressive human malignancies and is strongly associated with poor prognosis. The VGLL1 gene encodes for a co-transcriptional activator that shows intriguing structural similarity to key activators in the hippo pathway, providing important clues to its functional role. VGLL1 binds to TEAD transcription factors in an analogous fashion to YAP1 but appears to activate a distinct set of downstream gene targets. In mammals, VGLL1 expression is found almost exclusively in placental trophoblasts, cells that share many hallmarks of cancer. Due to its role as …

Towards A Better Mucolytic, Burton F Dickey, Christopher M Evans

Faculty, Staff and Student Publications

No abstract provided.

Disclosing Quantitative Rt-Pcr Raw Data During Manuscript Submission: A Call For Action, Andreas Untergasser, Jan Hellemans, Michael W Pfaffl, Jan M Ruijter, Maurice J B Van Den Hoff, Mihnea P Dragomir, Douglas Adamoski, Sandra Martha Gomes Dias, Rui Manuel Reis, Manuela Ferracin, Emmanuel Dias-Neto, Ian Marsh, Mikael Kubista, Muller Fabbri, Ajay Goel, Ondřej Slabý, Erik Knutsen, Baoqing Chen, Massimo Negrini, Koshi Mimori, Martin Pichler, Maria Papatriantafyllou, Simone Anfossi, Thomas D Schmittgen, Jim Huggett, Stephen Bustin, Jo Vandesompele, George A Calin, Heroic (The Initiative Group On Qrt Disclosure) Consortium

Faculty, Staff and Student Publications

Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and noncoding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To address the problem, we propose the following recommendations: (a) accurate documentation of experimental procedures in Materials and methods (and not only in the supplementary information, as many journals have a strict mandate for making Materials and methods as visible as possible in the main text); (b) submission of RT‐qPCR raw …

Quantitative Dual-Energy Ct Image Guidance For Thermochemical Ablation: In Vivo Results In The Rabbit Vx2 Model, Emily A Thompson, Natalie W Fowlkes, Megan C Jacobsen, Rick R Layman, Erik N K Cressman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the feasibility of using dual-energy computed tomography (CT) and theranostic cesium hydroxide (CsOH) for image guidance of thermochemical ablation (TCA) in a rabbit VX2 tumor model.

MATERIALS AND METHODS: In vivo experiments were performed on New Zealand white rabbits, where VX2 tumor fragments (0.3 mL) were inoculated into the right and left flanks (n = 16 rabbits, 32 tumors). Catheters were placed in the approximate center of 1- to 2-cm diameter tumors under ultrasound guidance. TCA was delivered in 1 of 3 treatment groups: untreated control, 5-M TCA, or 10-M TCA. The TCA base reagent was doped …

Impact Of Biomarker-Matched Therapies On Outcomes In Patients With Sarcoma Enrolled In Early-Phase Clinical Trials (Samba 101), Roberto Carmagnani Pestana, Justin T Moyers, Jason Roszik, Shiraj Sen, David S Hong, Aung Naing, Cynthia E Herzog, Siqing Fu, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Daniel D Karp, Apostolia M Tsimberidou, Shubham Pant, Maria A Zarzour, Ravin Ratan, Vinod Ravi, Robert S Benjamin, Alexander J Lazar, Wei-Lien Wang, Najat Daw, Jonathan B Gill, Douglas J Harrison, Valerae O Lewis, Christina L Roland, Shreyaskumar R Patel, J Andrew Livingston, Neeta Somaiah, Joseph A Ludwig, Anthony P Conley, Nelson Hamerschlak, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma.

Experimental design: In this retrospective analysis, investigational treatment characteristics and longitudinal survival outcomes were analyzed in patients with biopsy-confirmed sarcoma enrolled in early-phase trials at MD Anderson Cancer Center from May 2006 to July 2021.

Results: Five hundred eighty-seven patients were included [405 soft tissue, 122 bone, …

Resilience To Stress Across The Lifespan: Childhood Maltreatment, Heart Rate Variability, And Bereavement, Michelle A Chen, Robert Suchting, Julian F Thayer, Christopher P Fagundes

Faculty, Staff and Student Publications

Following a stressful life event, there is considerable variation in how individuals respond and adapt. Multiple models of risk and resilience show that adverse childhood experiences may be associated with an individual's response to stress later in life. While there is considerable support that early adversity can sensitize the stress response system and lead to adverse outcomes later in life, there is mounting evidence that in adolescence and young adulthood, certain biological predispositions to stress may be associated with resilience in the context of subsequent stressors. In this study, we evaluated how individual differences in vagally mediated heart rate variability …

Prospective Study Of Perioperative Circulating Tumor Dna Dynamics In Patients Undergoing Hepatectomy For Colorectal Liver Metastases, Timothy E Newhook, Michael J Overman, Yun Shin Chun, Arvind Dasari, Ching-Wei D Tzeng, Hop S Tran Cao, Victoria Raymond, Christine Parseghian, Benny Johnson, Yujiro Nishioka, Yoshikuni Kawaguchi, Abhineet Uppal, Timothy J Vreeland, Ariel Jaimovich, Elsa M Arvide, Jenilette V Cristo, Steven H Wei, Kanwal P Raghav, Van K Morris, Jeffrey E Lee, Scott Kopetz, Jean-Nicolas Vauthey

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.

SUMMARY BACKGROUND DATA: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.

METHODS: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.

RESULTS: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but …

Technique For Robotic Pancreaticojejunostomy, Derek J Erstad, Yuji Hatanaka, Samuel Cass, Jessica Maxwell, Hop Tran Cao, Michael Kim, Ching-Wei Tzeng, Jeffrey E Lee, Matthew Katz, Naruhiko Ikoma

Faculty, Staff and Student Publications

Background:: Minimally invasive, robotic techniques for hepatobiliary procedures offer the potential for accelerated recovery and reduced opioid usage. Robotic pancreaticoduodenectomy is a technically challenging procedure with a complex reconstruction. In this regard, standardization of the pancreaticojejunostomy technique is critical for safe adoption of robotic technology in pancreatic surgery.

Study Design:: In this video, we demonstrate the primary steps and associated principles to perform a robotic pancreaticojejunostomy using a modified Blumgart/Nagakawa technique.

Results:: Key steps to this procedure include: 1) exposure and positioning of the pancreatic remnant and jejunal limb; 2) transpancreatic suture placement using augmented sutures with bulldog clamps for …

Characterizing The Interplay Of Treatment Parameters And Complexity And Their Impact On Performance On An Iroc Imrt Phantom Using Machine Learning, Hunter Mehrens, Andrea Molineu, Nadia Hernandez, Laurence Court, Rebecca Howell, David Jaffray, Christine B Peterson, Julianne Pollard-Larkin, Stephen F Kry

Faculty, Staff and Student Publications

AIM OF THE STUDY: To elucidate the important factors and their interplay that drive performance on IMRT phantoms from the Imaging and Radiation Oncology Core (IROC).

METHODS: IROC's IMRT head and neck phantom contains two targets and an organ at risk. Point and 2D dose are measured by TLDs and film, respectively. 1,542 irradiations between 2012-2020 were retrospectively analyzed based on output parameters, complexity metrics, and treatment parameters. Univariate analysis compared parameters based on pass/fail, and random forest modeling was used to predict output parameters and determine the underlying importance of the variables.

RESULTS: The average phantom pass rate was …

Leveraging The Electronic Health Record To Implement Emergency Department Delirium Screening, Anita N Chary, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Christopher R Carpenter, Shan W Liu, Kyler M Godwin, Aanand D Naik, Hardeep Singh, Maura Kennedy

Faculty, Staff and Students Publications

OBJECTIVE: The aim of this study is to understand how emergency departments (EDs) use health information technology (HIT), and specifically the electronic health record (EHR), to support implementation of delirium screening.

METHODS: We conducted semi-structured interviews with 23 ED clinician-administrators, representing 20 EDs, about how they used HIT resources to implement delirium screening. Interviews focused on challenges participants experienced when implementing ED delirium screening and EHR-based strategies they used to overcome them. We coded interview transcripts using dimensions from the Singh and Sittig sociotechnical model, which addresses use of HIT in complex adaptive health care systems. Subsequently, we analyzed data …

Noninvasive Genomic Profiling Of Somatic Mutations In Oral Cavity Cancers, Yuanxin Xi, Marcelo V Negrao, Keiko Akagi, Weihong Xiao, Bo Jiang, Sarah C Warner, Joe Dan Dunn, Jing Wang, David E Symer, Maura L Gillison

Faculty, Staff and Student Publications

OBJECTIVES: Somatic mutations may predict prognosis, therapeutic response, or cancer progression. We evaluated targeted sequencing of oral rinse samples (ORS) for non-invasive mutational profiling of oral squamous cell carcinomas (OSCC).

MATERIALS AND METHODS: A custom hybrid capture panel targeting 42 frequently mutated genes in OSCC was used to identify DNA sequence variants in matched ORS and fresh-frozen tumors from 120 newly-diagnosed patients. Receiver operating characteristic (ROC) curves determined the optimal variant allele fraction (VAF) cutoff for variant discrimination in ORS. Behavioral, clinical, and analytical factors were evaluated for impacts on assay performance.

RESULTS: Half of tumors involved oral tongue (50 …

Alendronate Conjugate For Targeted Delivery To Bone-Forming Prostate Cancer, Jossana A Damasco, Guoyu Yu, Ajay Kumar, Joy Perez, Rio Carlo M Lirag, Elizabeth M Whitley, Sue-Hwa Lin, Marites P Melancon

Faculty, Staff and Student Publications

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, …

One Immune System Plays Many Parts: The Dynamic Role Of The Immune System In Chronic Pain And Opioid Pharmacology, Sanam Mustafa, Juliana E Bajic, Benjamin Barry, Samuel Evans, Kariel R Siemens, Mark R Hutchinson, Peter M Grace

Faculty, Staff and Student Publications

The transition from acute to chronic pain is an ongoing major problem for individuals, society and healthcare systems around the world. It is clear chronic pain is a complex multidimensional biological challenge plagued with difficulties in pain management, specifically opioid use. In recent years the role of the immune system in chronic pain and opioid pharmacology has come to the forefront. As a highly dynamic and versatile network of cells, tissues and organs, the immune system is perfectly positioned at the microscale level to alter nociception and drive structural adaptations that underpin chronic pain and opioid use. In this review, …

Predictors Of Perceived Functional Status In Early Systemic Sclerosis: A Prospective Longitudinal Study Of An Early Disease Cohort, Julia Chernis, Maryam Buni, Sarah Kazzaz, Jun Ying, Marka Lyons, Shervin Assassi, Maureen Mayes

Faculty, Staff and Student Publications

OBJECTIVE: The modified Health Assessment Questionnaire (M-HAQ) is a well-established patient-reported outcome measure in systemic sclerosis (SSc) studies that reflects how a patient functions in several categories of activities of daily living. This study analyzed clinical, demographic, and socioeconomic factors that predict M-HAQ scores over time.

METHODS: This study included 388 patients with baseline M-HAQ scores from the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) early disease cohort with a mean disease duration of 2.5 years, mean follow-up time of 3.9 years, and median follow-up of 7.2 years. A total of 1,950 M-HAQ measurements were analyzed. Baseline disease characteristics …

Applicability And Usage Of Dose Mapping/Accumulation In Radiotherapy, Martina Murr, Kristy K Brock, Marco Fusella, Nicholas Hardcastle, Mohammad Hussein, Michael G Jameson, Isak Wahlstedt, Johnson Yuen, Jamie R Mcclelland, Eliana Vasquez Osorio

Faculty, Staff and Student Publications

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of …

Fully Human Monoclonal Antibody Targeting Activated Adam10 On Colorectal Cancer Cells, Nayanendu Saha, Du-San Baek, Rachelle P Mendoza, Dorothea Robev, Yan Xu, Yehuda Goldgur, M Jason De La Cruz, Elisa De Stanchina, Peter W Janes, Kai Xu, Dimiter S Dimitrov, Dimitar B Nikolov

Faculty, Staff and Student Publications

Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initiated upon Notch cleavage by the metalloprotease ADAM10. It has been shown that ADAM10 overexpression correlates with aberrant signaling from Notch, erbBs, and other receptors, as well as a more aggressive metastatic phenotype, in a range of cancers including colon, gastric, prostate, breast, ovarian, uterine, and leukemia. ADAM10 inhibition, therefore, stands out as an important and new approach to deter the progression of advanced CRC. For targeting the ADAM10 substrate-binding region, which is located …

Apoptotic Cell Death In Disease-Current Understanding Of The Nccd 2023, Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A Aaronson, John M Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S Alnemri, Lucia Altucci, Ivano Amelio, David W Andrews, Rami I Aqeilan, Eli Arama, Eric H Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A Barlev, Jiri Bartek, Nicolas G Bazan, Christoph Becker, Francesca Bernassola, Mathieu J M Bertrand, Marco E Bianchi, Mikhail V Blagosklonny, J Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H Chen, Emily H Cheng, Jerry E Chipuk, John A Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R Cubillos-Ruiz, Peter E Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M Dawson, Valina L Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J Dixon, Brian D Dynlacht, Wafik S El-Deiry, John W Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J Garcia-Saez, Abhishek D Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R Green, Lloyd A Greene, Hinrich Gronemeyer, Georg Häcker, György Hajnóczky, J Marie Hardwick, Ygal Haupt, Sudan He, David M Heery, Michael O Hengartner, Claudio Hetz, David A Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jäättelä, Ana Janic, Bertrand Joseph, Philipp J Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L Kelly, Oliver Kepp, Adi Kimchi, Richard N Kitsis, Daniel J Klionsky, Ruth Kluck, Dmitri V Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N Lavrik, John J Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A Lipton, Richard A Lockshin, Carlos López-Otín, Tom Luedde, Marion Macfarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J Martin, Jean-Claude Martinou, Pier G Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A Miao, Ute M Moll, Cristina Muñoz-Pinedo, Daniel J Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Núñez, Andrew Oberst, Dimitry Ofengeim, Joseph T Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M Penninger, Francesca Pentimalli, David M Pereira, Shazib Pervaiz, Marcus E Peter, Paolo Pinton, Giovanni Porta, Jochen H M Prehn, Hamsa Puthalakath, Gabriel A Rabinovich, Krishnaraj Rajalingam, Kodi S Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M P Rodrigues, Barak Rotblat, Carla V Rothlin, David C Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M Ryan, Kristopher A Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W G Tait, Daolin Tang, Nektarios Tavernarakis, Carol M Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G Vander Heiden, Jacqueline L Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia Von Karstedt, Anne K Voss, Karen H Vousden, Domagoj Vucic, Daniela Vuri, Erwin F Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi

Faculty, Staff and Student Publications

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. …

Advances In The Treatment Of Invasive Fungal Disease, Zhuan Zhang, Gerald F Bills, Zhiqiang An

Faculty, Staff and Student Publications

With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of …