Biomedical Informatics Commons^™

High-Dose Once-Daily Thoracic Radiotherapy In Limited-Stage Small-Cell Lung Cancer: Calgb 30610 (Alliance)/Rtog 0538, Jeffrey Bogart, Xiaofei Wang, Gregory Masters, Junheng Gao, Ritsuko Komaki, Laurie E Gaspar, John Heymach, James Bonner, Charles Kuzma, Saiama Waqar, William Petty, Thomas E Stinchcombe, Jeffrey D Bradley, Everett Vokes

Faculty, Staff and Student Publications

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.

METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity …

National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im

Faculty, Staff and Student Publications

Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision …

Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe

Faculty, Staff and Student Publications

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …

Combining Mendelian Randomization And Network Deconvolution For Inference Of Causal Networks With Gwas Summary Data, Zhaotong Lin, Haoran Xue, Wei Pan

Faculty, Staff and Student Publications

Mendelian randomization (MR) has been increasingly applied for causal inference with observational data by using genetic variants as instrumental variables (IVs). However, the current practice of MR has been largely restricted to investigating the total causal effect between two traits, while it would be useful to infer the direct causal effect between any two of many traits (by accounting for indirect or mediating effects through other traits). For this purpose we propose a two-step approach: we first apply an extended MR method to infer (i.e. both estimate and test) a causal network of total effects among multiple traits, then we …

Philadelphia-Like Genetic Rearrangements In Adults With B-Cell All: Refractoriness To Chemotherapy And Response To Tyrosine Kinase Inhibitor In Abl Class Rearrangements, Jayastu Senapati, Elias Jabbour, Marina Konopleva, Nicholas J Short, Guilin Tang, Naval Daver, Partow Kebriaei, Tapan Kadia, Naveen Pemmaraju, Koichi Takahashi, Courtney Dinardo, Koji Sasaki, Gautam Borthakur, Beenu Thakral, Rashmi Kanagal-Shamanna, Keyur Patel, Farhad Ravandi, Kathryn Roberts, Charles Mullighan, Hagop Kantarjian, Nitin Jain

Faculty, Staff and Student Publications

PURPOSE: Philadelphia-like (Ph-like) B-cell ALL is a high-risk subtype of B-cell ALL that shares a gene expression profile with Ph-positive ALL, but without a

PATIENTS AND METHODS: We performed a retrospective review of patients with B-cell ALL treated at MD Anderson Cancer Center to identify recurrent genetic fusions commonly seen in Ph-like ALL and focus on patients treated with TKI.

RESULTS: We identified 23 patients with recurrent genetic fusions commonly seen in Ph-like ALL; 14 had

CONCLUSION: Understanding the genomics of B-cell ALL is important for disease prognostication and for precise treatment planning. Besides conventional cytogenetics and directed FISH testing, …

Critical Role Of The Ventral Temporal Lobe In Naming, Kathryn M Snyder, Kiefer J Forseth, Cristian Donos, Patrick S Rollo, Simon Fischer-Baum, Joshua Breier, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia.

METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and …

Aapm Task Group Report 305: Guidance For Standardization Of Vendor-Neutral Reject Analysis In Radiography, Kevin Little, Ingrid Reiser, Bruce Apgar, Poonam Dalal, Jaydev Dave, Ryan Fisher, Katie Hulme, Mary Ellen Jafari, Emily Marshall, Stephen Meyer, Quentin Moore, Nicole Murphy, Thomas Nishino, Katelyn Nye, Kevin O'Donnell, John Sabol, Adrian Sanchez, William Sensakovic, Lawrence Tarbox, Robert Uzenoff, Alisa Walz-Flannigan, Charles Willis, Jie Zhang

Faculty, Staff and Student Publications

Reject rate analysis is considered an integral part of a diagnostic radiography quality control (QC) program. A rejected image is a patient radiograph that was not presented to a radiologist for diagnosis and that contributes unnecessary radiation dose to the patient. Reject rates that are either too high or too low may suggest systemic department shortcomings in QC mechanisms. Due to the lack of standardization, reject data often cannot be easily compared between radiography systems from different vendors. The purpose of this report is to provide guidance to help standardize data elements that are required for comprehensive reject analysis and …

Phase I Trial Of Autologous Rna-Electroporated Cmet-Directed Car T Cells Administered Intravenously In Patients With Melanoma And Breast Carcinoma, Payal D Shah, Alexander C Huang, Xiaowei Xu, Robert Orlowski, Ravi K Amaravadi, Lynn M Schuchter, Paul Zhang, Julia Tchou, Tina Matlawski, Amanda Cervini, Joanne Shea, Joan Gilmore, Lester Lledo, Karen Dengel, Amy Marshall, E John Wherry, Gerald P Linette, Andrea Brennan, Vanessa Gonzalez, Irina Kulikovskaya, Simon F Lacey, Gabriela Plesa, Carl H June, Robert H Vonderheide, Tara C Mitchell

Faculty, Staff and Student Publications

PURPOSE: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET.

EXPERIMENTAL DESIGN: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated.

RESULTS: Mean age was …

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 …

Neural Network Based Ensemble Model To Predict Radiation Induced Lymphopenia After Concurrent Chemo-Radiotherapy For Non-Small Cell Lung Cancer From Two Institutions, Yejin Kim, Ibrahim Chamseddine, Yeona Cho, Jin Sung Kim, Radhe Mohan, Nadya Shusharina, Harald Paganetti, Steven Lin, Hong In Yoon, Seungryong Cho, Clemens Grassberger

Faculty, Staff and Student Publications

The use of adjuvant Immune Checkpoint Inhibitors (ICI) after concurrent chemo-radiation therapy (CCRT) has become the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, prolonged radiotherapy regimens are known to cause radiation-induced lymphopenia (RIL), a long-neglected toxicity that has been shown to correlate with response to ICIs and survival of patients treated with adjuvant ICI after CCRT. In this study, we aim to develop a novel neural network (NN) approach that integrates patient characteristics, treatment related variables, and differential dose volume histograms (dDVH) of lung and heart to predict the incidence of RIL at the end …

Genome-Wide Analysis Of Structural Variants In Parkinson Disease, Kimberley J Billingsley, Jinhui Ding, Pilar Alvarez Jerez, Anastasia Illarionova, Kristin Levine, Francis P Grenn, Mary B Makarious, Anni Moore, Daniel Vitale, Xylena Reed, Dena Hernandez, Ali Torkamani, Mina Ryten, John Hardy, Uk Brain Expression Consortium (Ukbec), Ruth Chia, Sonja W Scholz, Bryan J Traynor, Clifton L Dalgard, Debra J Ehrlich, Toshiko Tanaka, Luigi Ferrucci, Thomas G Beach, Geidy E Serrano, John P Quinn, Vivien J Bubb, Ryan L Collins, Xuefang Zhao, Mark Walker, Emma Pierce-Hoffman, Harrison Brand, Michael E Talkowski, Bradford Casey, Mark R Cookson, Androo Markham, Mike A Nalls, Medhat Mahmoud, Fritz J Sedlazeck, Cornelis Blauwendraat, J Raphael Gibbs, Andrew B Singleton

Faculty, Staff and Students Publications

OBJECTIVE: Identification of genetic risk factors for Parkinson disease (PD) has to date been primarily limited to the study of single nucleotide variants, which only represent a small fraction of the genetic variation in the human genome. Consequently, causal variants for most PD risk are not known. Here we focused on structural variants (SVs), which represent a major source of genetic variation in the human genome. We aimed to discover SVs associated with PD risk by performing the first large-scale characterization of SVs in PD.

METHODS: We leveraged a recently developed computational pipeline to detect and genotype SVs from 7,772 …

Commentary: Sponsoring Scholarship: Mountains Moved By The American Association For Thoracic Surger, Bryan M Burt

Faculty, Staff and Students Publications

No abstract provided.

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, …

Structural Basis Of The Alkaline Ph-Dependent Activation Of Insulin Receptor-Related Receptor, Liwei Wang, Catherine Hall, Jie Li, Eunhee Choi, Xiao-Chen Bai

Faculty, Staff and Student Publications

The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose activation requires ligand binding, insulin receptor-related receptor (IRR)-the third member of the IR family-is activated by alkaline pH. However, the molecular mechanism underlying alkaline pH-induced IRR activation remains unclear. Here, we present cryo-EM structures of human IRR in both neutral pH inactive and alkaline pH active states. Combined with mutagenesis and cellular assays, we show that, upon pH increase, electrostatic repulsion of the pH-sensitive motifs of IRR disrupts its autoinhibited state …

Development And Validation Of A Patient-Reported Outcome Measure To Assess Symptom Burden After Chimeric Antigen Receptor T-Cell Therapy, Xin Shelley Wang, Samer A Srour, Tito Mendoza, Meagan Whisenant, Ishwaria Subbiah, Elizabeth Gonzalez, Mona Kamal, Shu-En Shen, Charles Cleeland, Partow Kebriaei, Katayoun Rezvani, Sattva Neelapu, Sairah Ahmed, Elizabeth Shpall

Faculty, Staff and Student Publications

This cross-sectional study aimed to develop and validate a patient-reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T-cell therapy, the MD Anderson Symptom Inventory (MDASI-CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single-item quality-of-life (QoL) measure and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI-CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, …

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 …

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, …

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 …

Higher Hippocampal Diffusivity Values In Welders Are Associated With Greater R2* In The Red Nucleus And Lower Psychomotor Performance, Eun-Young Lee, Juhee Kim, Janina Manzieri Prado-Rico, Guangwei Du, Mechelle M Lewis, Lan Kong, Byoung-Gwon Kim, Young-Seoub Hong, Jeff D Yanosky, Richard B Mailman, Xuemei Huang

Faculty, Staff and Student Publications

INTRODUCTION: Chronic excessive welding exposure may be related to higher metal accumulation and structural differences in different subcortical structures. We examined how welding affected brain structures and their associations with metal exposure and neurobehavioral consequences.

METHODS: Study includes 42 welders and 31 controls without a welding history. Welding-related structural differences were assessed by volume and diffusion tensor imaging (DTI) metrics in basal ganglia, red nucleus (RN), and hippocampus. Metal exposure was estimated by both exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by R1 (for Mn) and R2* (for Fe). Neurobehavioral status was assessed by standard …

Family Caregiver Reports Of Their Own And Patient Symptoms In Cancer Home Hospice Approaching End-Of-Life, Maija Reblin, Eli Iacob, Djin L Tay, Hui Li, Megan C Thomas Hebdon, Anna Beck, Gary Donaldson, Kristin G Cloyes, Lee Ellington

Faculty, Staff and Student Publications

Context: Family caregivers assume the primary responsibility of assessing and managing hospice cancer patient symptoms while simultaneously managing their own wellbeing and symptoms. Objectives: Describe caregivers' assessment of hospice cancer patient and their own symptoms during the last 60 days of patient life, and assess the relationship between patient and caregiver symptoms over time.

Methods: Caregiver symptom report of self and cancer home hospice patient symptom data were collected via telephone in the final 60 days of patient life. Descriptive data on symptom severity and prevalence were summarized. Exploratory Factor Analysis was used to group individual symptoms. …

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, …

Late-Onset Cognitive Impairment And Modifiable Risk Factors In Adult Childhood Cancer Survivors, Nicholas S Phillips, Kayla L Stratton, Annalynn M Williams, Tim Ahles, Kirsten K Ness, Harvey Jay Cohen, Kim Edelstein, Yutaka Yasui, Kevin Oeffinger, Eric J Chow, Rebecca M Howell, Leslie L Robison, Gregory T Armstrong, Wendy M Leisenring, Kevin R Krull

Faculty, Staff and Student Publications

Importance: Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood.

Objective: To determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments.

Design, setting, and participants: Participants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was …

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 …

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. …

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 …

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 …

Integrated Circulating Tumor Dna And T Cell Repertoire Predict Radiotherapeutic Response And Outcome In Non-Small Cell Lung Cancer Patients With Brain Metastasis, Ling Peng, Yawen Bin, Peng Ding, Lingjuan Chen, Hao Zeng, Zelong Xu, Liyan Ji, Xuan Gao, Pian Liu, Ye Wang, Sheng Zhang, Zhongxing Liao, Xuefeng Xia, Ruiguang Zhang, Fan Tong, Xiaorong Dong

Faculty, Staff and Student Publications

No abstract provided.

Potent Antitumor Activity Of Ensartinib In Met Exon 14 Skipping-Mutated Non-Small Cell Lung Cancer, Yang Xia, Rui Jin, Miao Li, Fen Lan, Hao Zhu, Yinghui Yu, Da Miao, Qiyuan Wang, Yi Zhou, Giovanni Selvaggi, Songmin Ying, Jianjun Zhang, Huahao Shen, Xiuning Le, Wen Li

Faculty, Staff and Student Publications

Met proto-oncogene exon 14 skipping (METex14) mutations are targetable driver genes in approximately 3% of non-small-cell lung cancers (NSCLCs). Ensartinib, a type Ia MET inhibitor, is a multi-kinase inhibitor that has been approved for ALK-positive NSCLCs. Ensartinib was administered for compassionate use (cohort 1) and in a phase II clinical trial (cohort 2) to patients with METex14 mutant NSCLCs, with ORR as a primary endpoint. Molecular simulation was conducted to evaluate ensartinib c-MET interaction, and cell lines, patient-derived organoids (PDOs), and xenograft models were used to test the effectiveness of ensartinib. Among 29 evaluable patients, the ORR and DCR of …

Younger Haploidentical Donor Versus Older Matched Unrelated Donor For Patients With Aml/Mds, Curtis Marcoux, David Marin, Jeremy Ramdial, Gheath Alatrash, Amin M Alousi, Betul Oran, Partow Kebriaei, Uday R Popat, Katayoun Rezvani, Richard E Champlin, Elizabeth J Shpall, Rohtesh S Mehta

Faculty, Staff and Student Publications

Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with older MUDs. Therefore, we performed a retrospective analysis comparing outcomes of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients who underwent HCT with younger (≤35 years) haploidentical donors (n = 494) or older (>35 years) MUDs (n = 1005). Patients in the haploidentical …

Sting Agonist-Loaded Mesoporous Manganese-Silica Nanoparticles For Vaccine Applications, Cheng Xu, Hannah E Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W Tai, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the …