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Articles 5941 - 5970 of 7878

Full-Text Articles in Medicine and Health Sciences

Predictors Of Oncologic Outcome In Patients Receiving Phase I Investigational Therapy For Recurrent Or Metastatic Cervical Cancer, Ji Son, Heather Y Lin, Siqing Fu, Amadeo B Biter, Ecaterina E Dumbrava, Daniel D Karp, Aung Naing, Shubham Pant, Sarina A Piha-Paul, Jordi Rodon, Vivek Subbiah, Apostolia M Tsimberidou, Timothy A Yap, Michael M Frumovitz, Amir A Jazaeri, Pedro T Ramirez, Shannon N Westin, Ying Yuan, Funda Meric-Bernstam, David S Hong Feb 2023

Predictors Of Oncologic Outcome In Patients Receiving Phase I Investigational Therapy For Recurrent Or Metastatic Cervical Cancer, Ji Son, Heather Y Lin, Siqing Fu, Amadeo B Biter, Ecaterina E Dumbrava, Daniel D Karp, Aung Naing, Shubham Pant, Sarina A Piha-Paul, Jordi Rodon, Vivek Subbiah, Apostolia M Tsimberidou, Timothy A Yap, Michael M Frumovitz, Amir A Jazaeri, Pedro T Ramirez, Shannon N Westin, Ying Yuan, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials.

METHODS: Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed.

RESULTS: We included 65 patients with a median age of 41 years (range, 20-74), 3 prior therapies (range, 1-7), and 67.7% squamous carcinoma. The …


Retrospective Evaluation Of The Role Of Gemcitabine-Docetaxel In Well-Differentiated And Dedifferentiated Liposarcoma, Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei-Lien Wang, Jeffrey M Cloutier, Elise F Nassif, Emily Z Keung, Christina L Roland, Barry Feig, Dejka Araujo, Robert S Benjamin, Anthony P Conley, John A Livingston, Joseph Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah Feb 2023

Retrospective Evaluation Of The Role Of Gemcitabine-Docetaxel In Well-Differentiated And Dedifferentiated Liposarcoma, Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei-Lien Wang, Jeffrey M Cloutier, Elise F Nassif, Emily Z Keung, Christina L Roland, Barry Feig, Dejka Araujo, Robert S Benjamin, Anthony P Conley, John A Livingston, Joseph Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah

Faculty, Staff and Student Publications

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS.

METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups.

RESULTS: Sixty-five WDLPS/DDLPS patients …


Malignant Transformation By Oncogenic K-Ras Requires Idh2-Mediated Reductive Carboxylation To Promote Glutamine Utilization, Rui Liu, Panpan Liu, Huichang Bi, Jianhua Ling, Huiqin Zhang, Mingquan Zhang, Yumin Hu, Paul J Chiao, Peng Huang, Jinyun Liu Feb 2023

Malignant Transformation By Oncogenic K-Ras Requires Idh2-Mediated Reductive Carboxylation To Promote Glutamine Utilization, Rui Liu, Panpan Liu, Huichang Bi, Jianhua Ling, Huiqin Zhang, Mingquan Zhang, Yumin Hu, Paul J Chiao, Peng Huang, Jinyun Liu

Faculty, Staff and Student Publications

No abstract provided.


Mental Health, War Trauma, And Migration: The Contribution Of Comprehensive Psychoneuroendocrinology, Robert Dantzer Feb 2023

Mental Health, War Trauma, And Migration: The Contribution Of Comprehensive Psychoneuroendocrinology, Robert Dantzer

Faculty, Staff and Student Publications

No abstract provided.


Automatic Diagnosis Of Late-Life Depression By 3d Convolutional Neural Networks And Cross-Sample Entropy Analysis From Resting-State Fmri, Chemin Lin, Shwu-Hua Lee, Chih-Mao Huang, Guan-Yen Chen, Wei Chang, Ho-Ling Liu, Shu-Hang Ng, Tatia Mei-Chun Lee, Shun-Chi Wu Feb 2023

Automatic Diagnosis Of Late-Life Depression By 3d Convolutional Neural Networks And Cross-Sample Entropy Analysis From Resting-State Fmri, Chemin Lin, Shwu-Hua Lee, Chih-Mao Huang, Guan-Yen Chen, Wei Chang, Ho-Ling Liu, Shu-Hang Ng, Tatia Mei-Chun Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Resting-state fMRI has been widely used in investigating the pathophysiology of late-life depression (LLD). Unlike the conventional linear approach, cross-sample entropy (CSE) analysis shows the nonlinear property in fMRI signals between brain regions. Moreover, recent advances in deep learning, such as convolutional neural networks (CNNs), provide a timely application for understanding LLD. Accurate and prompt diagnosis is essential in LLD; hence, this study aimed to combine CNN and CSE analysis to discriminate LLD patients and non-depressed comparison older adults based on brain resting-state fMRI signals. Seventy-seven older adults, including 49 patients and 28 comparison older adults, were included for fMRI …


Clinical Features Associated With Outcomes And Biomarker Analysis Of Dabrafenib Plus Trametinib Treatment In Patients With Braf-Mutant Melanoma Brain Metastases, James S Wilmott, Hussein Tawbi, Johnathan A Engh, Nduka M Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A Vergara, Hansol Lee, Peter A Johansson, Peter M Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H Butterfield, Richard A Scolyer, John M Kirkwood, Georgina V Long, Michael A Davies Feb 2023

Clinical Features Associated With Outcomes And Biomarker Analysis Of Dabrafenib Plus Trametinib Treatment In Patients With Braf-Mutant Melanoma Brain Metastases, James S Wilmott, Hussein Tawbi, Johnathan A Engh, Nduka M Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A Vergara, Hansol Lee, Peter A Johansson, Peter M Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H Butterfield, Richard A Scolyer, John M Kirkwood, Georgina V Long, Michael A Davies

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).

PATIENTS AND METHODS: Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate …


Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green Feb 2023

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …


A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, Fuu-Jen Tsai Feb 2023

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, Fuu-Jen Tsai

Faculty, Staff and Student Publications

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The …


The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer Feb 2023

The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer

Faculty, Staff and Student Publications

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral …


Tissue-Resident Memory T Cells Trigger Rapid Exudation And Local Antibody Accumulation, Pamela C Rosato, Sahar Lotfi-Emran, Vineet Joag, Sathi Wijeyesinghe, Clare F Quarnstrom, Hanna N Degefu, Rebecca Nedellec, Jason M Schenkel, Lalit K Beura, Lars Hangartner, Dennis R Burton, David Masopust Feb 2023

Tissue-Resident Memory T Cells Trigger Rapid Exudation And Local Antibody Accumulation, Pamela C Rosato, Sahar Lotfi-Emran, Vineet Joag, Sathi Wijeyesinghe, Clare F Quarnstrom, Hanna N Degefu, Rebecca Nedellec, Jason M Schenkel, Lalit K Beura, Lars Hangartner, Dennis R Burton, David Masopust

Faculty, Staff and Student Publications

Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells (TRM) in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in …


Hematopoietic Cell Transplantation In The Management Of Myelodysplastic Syndrome: An Evidence-Based Review From The American Society For Transplantation And Cellular Therapy Committee On Practice Guidelines, Zachariah Defilipp, Stefan O Ciurea, Corey Cutler, Marie Robin, Erica D Warlick, Ryotaro Nakamura, Andrew M Brunner, Bhagirathbhai Dholaria, Alison R Walker, Nicolaus Kröger, Nelli Bejanyan, Ehab Atallah, Roni Tamari, Melhem M Solh, Mary-Elizabeth Percival, Marcos De Lima, Bart Scott, Betul Oran, Guillermo Garcia-Manero, Mehdi Hamadani, Paul Carpenter, Amy E Dezern Feb 2023

Hematopoietic Cell Transplantation In The Management Of Myelodysplastic Syndrome: An Evidence-Based Review From The American Society For Transplantation And Cellular Therapy Committee On Practice Guidelines, Zachariah Defilipp, Stefan O Ciurea, Corey Cutler, Marie Robin, Erica D Warlick, Ryotaro Nakamura, Andrew M Brunner, Bhagirathbhai Dholaria, Alison R Walker, Nicolaus Kröger, Nelli Bejanyan, Ehab Atallah, Roni Tamari, Melhem M Solh, Mary-Elizabeth Percival, Marcos De Lima, Bart Scott, Betul Oran, Guillermo Garcia-Manero, Mehdi Hamadani, Paul Carpenter, Amy E Dezern

Faculty, Staff and Student Publications

The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS …


Erratum: "Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment", Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada Feb 2023

Erratum: "Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment", Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada

Faculty, Staff and Student Publications

No abstract provided.


Effects Of Subnormothermic Regulated Hepatic Reperfusion On Mitochondrial And Transcriptomic Profiles In A Porcine Model, Joohyun Kim, Michael A Zimmerman, Woo Young Shin, Brent T Boettcher, Ju-Seog Lee, Jong-In Park, Muhammed Ali, Meiying Yang, Jyotsna Mishra, Catherine E Hagen, Joseph E Mcgraw, Angela Mathison, Harvey J Woehlck, Gwen Lomberk, Amadou K S Camara, Raul A Urrutia, David F Stowe, Johnny C Hong Feb 2023

Effects Of Subnormothermic Regulated Hepatic Reperfusion On Mitochondrial And Transcriptomic Profiles In A Porcine Model, Joohyun Kim, Michael A Zimmerman, Woo Young Shin, Brent T Boettcher, Ju-Seog Lee, Jong-In Park, Muhammed Ali, Meiying Yang, Jyotsna Mishra, Catherine E Hagen, Joseph E Mcgraw, Angela Mathison, Harvey J Woehlck, Gwen Lomberk, Amadou K S Camara, Raul A Urrutia, David F Stowe, Johnny C Hong

Faculty, Staff and Student Publications

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model.

SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation.

METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), …


Fucosylation Of Hla-Drb1 Regulates Cd4+ T Cell-Mediated Anti-Melanoma Immunity And Enhances Immunotherapy Efficacy, Daniel K Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B Williamson, Dennie T Frederick, Tatyana Sharova, Michael G White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan Mccarthy, Carlos Moransegura, Jane Messina, Kerry L Thomas, Lancia Darville, Victoria Izumi, John M Koomen, Shari A Pilon-Thomas, Brian Ruffell, Vincent C Luca, Robert S Haltiwanger, Xuefeng Wang, Jennifer A Wargo, Genevieve M Boland, Eric K Lau Feb 2023

Fucosylation Of Hla-Drb1 Regulates Cd4+ T Cell-Mediated Anti-Melanoma Immunity And Enhances Immunotherapy Efficacy, Daniel K Lester, Chase Burton, Alycia Gardner, Patrick Innamarato, Krithika Kodumudi, Qian Liu, Emma Adhikari, Qianqian Ming, Daniel B Williamson, Dennie T Frederick, Tatyana Sharova, Michael G White, Joseph Markowitz, Biwei Cao, Jonathan Nguyen, Joseph Johnson, Matthew Beatty, Andrea Mockabee-Macias, Matthew Mercurio, Gregory Watson, Pei-Ling Chen, Susan Mccarthy, Carlos Moransegura, Jane Messina, Kerry L Thomas, Lancia Darville, Victoria Izumi, John M Koomen, Shari A Pilon-Thomas, Brian Ruffell, Vincent C Luca, Robert S Haltiwanger, Xuefeng Wang, Jennifer A Wargo, Genevieve M Boland, Eric K Lau

Faculty, Staff and Student Publications

Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of l-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance …


The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel Feb 2023

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …


Hetrombopag Plus Porcine Atg And Cyclosporine For The Treatment Of Aplastic Anaemia: Early Outcomes Of A Prospective Pilot Study, Wenrui Yang, Xin Zhao, Xu Liu, Youzhen Xiong, Huihui Fan, Li Zhang, Jianping Li, Lei Ye, Kang Zhou, Yuan Li, Yang Yang, Guangxin Peng, Liping Jing, Fengkui Zhang Feb 2023

Hetrombopag Plus Porcine Atg And Cyclosporine For The Treatment Of Aplastic Anaemia: Early Outcomes Of A Prospective Pilot Study, Wenrui Yang, Xin Zhao, Xu Liu, Youzhen Xiong, Huihui Fan, Li Zhang, Jianping Li, Lei Ye, Kang Zhou, Yuan Li, Yang Yang, Guangxin Peng, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At …


Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist Feb 2023

Adverse Pregnancy Outcomes And Long Term Risk Of Ischemic Heart Disease In Mothers: National Cohort And Co-Sibling Study, Casey Crump, Jan Sundquist, Mary Ann Mclaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

DESIGN: National cohort study.

SETTING: Sweden.

PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015.

MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy …


Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu Feb 2023

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …


Profiling Human Pathogenic Repeat Expansion Regions By Synergistic And Multi-Level Impacts On Molecular Connections, Cong Fan, Ken Chen, Yukai Wang, Edward V Ball, Peter D Stenson, Matthew Mort, Albino Bacolla, Hildegard Kehrer-Sawatzki, John A Tainer, David N Cooper, Huiying Zhao Feb 2023

Profiling Human Pathogenic Repeat Expansion Regions By Synergistic And Multi-Level Impacts On Molecular Connections, Cong Fan, Ken Chen, Yukai Wang, Edward V Ball, Peter D Stenson, Matthew Mort, Albino Bacolla, Hildegard Kehrer-Sawatzki, John A Tainer, David N Cooper, Huiying Zhao

Faculty, Staff and Student Publications

Whilst DNA repeat expansions cause numerous heritable human disorders, their origins and underlying pathological mechanisms are often unclear. We collated a dataset comprising 224 human repeat expansions encompassing 203 different genes, and performed a systematic analysis with respect to key topological features at the DNA, RNA and protein levels. Comparison with controls without known pathogenicity and genomic regions lacking repeats, allowed the construction of the first tool to discriminate repeat regions harboring pathogenic repeat expansions (DPREx). At the DNA level, pathogenic repeat expansions exhibited stronger signals for DNA regulatory factors (e.g. H3K4me3, transcription factor-binding sites) in exons, promoters, 5'UTRs and …


Incidence Of Postoperative Complications Following Pancreatectomy For Pancreatic Cystic Lesions Or Pancreatic Cancer, Eileen C Donovan, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Jessica E Maxwell, Naruhiko Ikoma, Ching-Wei D Tzeng, Matthew H G Katz, Jeffrey E Lee, Michael P Kim Feb 2023

Incidence Of Postoperative Complications Following Pancreatectomy For Pancreatic Cystic Lesions Or Pancreatic Cancer, Eileen C Donovan, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Jessica E Maxwell, Naruhiko Ikoma, Ching-Wei D Tzeng, Matthew H G Katz, Jeffrey E Lee, Michael P Kim

Faculty, Staff and Student Publications

Background: In contrast to pancreatic ductal adenocarcinoma (PDAC), the risks of pancreatectomy for mucinous pancreatic cysts (MCs) are balanced against the putative goal of removing potentially malignant tumors. Despite undergoing similar operations, different rates of perioperative complications and morbidity between MC and PDAC patient populations may affect recommendations for resection. We therefore sought to compare the rates of postoperative complications between patients undergoing pancreatectomies for MCs or PDAC.

Methods: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for MCs or PDAC from July 2011 to August 2019. Patient demographics, complications, and perioperative data were …


A 24-Month Updated Analysis Of The Comparative Effectiveness Of Zuma-5 (Axi-Cel) Vs Scholar-5 External Control In Relapsed/Refractory Follicular Lymphoma, M Lia Palomba, Paola Ghione, Anik R Patel, Myrna Nahas, Sara Beygi, Anthony J Hatswell, Steve Kanters, Eve H Limbrick-Oldfield, Sally W Wade, Markqayne D Ray, Jessica Owen, Sattva S Neelapu, John Gribben, John Radford, Sabela Bobillo Feb 2023

A 24-Month Updated Analysis Of The Comparative Effectiveness Of Zuma-5 (Axi-Cel) Vs Scholar-5 External Control In Relapsed/Refractory Follicular Lymphoma, M Lia Palomba, Paola Ghione, Anik R Patel, Myrna Nahas, Sara Beygi, Anthony J Hatswell, Steve Kanters, Eve H Limbrick-Oldfield, Sally W Wade, Markqayne D Ray, Jessica Owen, Sattva S Neelapu, John Gribben, John Radford, Sabela Bobillo

Faculty, Staff and Student Publications

Background: In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data.

Research design and methods: The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response …


Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella Feb 2023

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …


Sox17: A Highly Sensitive And Specific Immunomarker For Ovarian And Endometrial Carcinomas, Xudong Zhang, Jun Yao, Na Niu, Xiaoran Li, Yan Liu, Lei Huo, Elizabeth D Euscher, Huamin Wang, Diana Bell, Anil K Sood, Guoliang Wang, Barrett C Lawson, Preetha Ramalingam, Anais Malpica, Aysegul A Sahin, Qingqing Ding, Jinsong Liu Feb 2023

Sox17: A Highly Sensitive And Specific Immunomarker For Ovarian And Endometrial Carcinomas, Xudong Zhang, Jun Yao, Na Niu, Xiaoran Li, Yan Liu, Lei Huo, Elizabeth D Euscher, Huamin Wang, Diana Bell, Anil K Sood, Guoliang Wang, Barrett C Lawson, Preetha Ramalingam, Anais Malpica, Aysegul A Sahin, Qingqing Ding, Jinsong Liu

Faculty, Staff and Student Publications

PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 …


Risks Of Mortality And Severe Coronavirus Disease 19 (Covid-19) Outcomes In Patients With Or Without Systemic Lupus Erythematosus, Sebastian Bruera, Xiudong Lei, Hui Zhao, Jinoos Yazdany, Mariana Chavez-Macgregor, Sharon H Giordano, Maria E Suarez-Almazor Feb 2023

Risks Of Mortality And Severe Coronavirus Disease 19 (Covid-19) Outcomes In Patients With Or Without Systemic Lupus Erythematosus, Sebastian Bruera, Xiudong Lei, Hui Zhao, Jinoos Yazdany, Mariana Chavez-Macgregor, Sharon H Giordano, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVES: We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes.

METHODS: This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE …


Superior Verbal Learning And Memory In Pediatric Brain Tumor Survivors Treated With Proton Versus Photon Radiotherapy, Lisa E Mash, Lisa S Kahalley, M Fatih Okcu, David R Grosshans, Arnold C Paulino, Heather Stancel, Luz De Leon, Elisabeth Wilde, Nilesh Desai, Zili D Chu, William E Whitehead, Murali Chintagumpala, Kimberly P Raghubar Feb 2023

Superior Verbal Learning And Memory In Pediatric Brain Tumor Survivors Treated With Proton Versus Photon Radiotherapy, Lisa E Mash, Lisa S Kahalley, M Fatih Okcu, David R Grosshans, Arnold C Paulino, Heather Stancel, Luz De Leon, Elisabeth Wilde, Nilesh Desai, Zili D Chu, William E Whitehead, Murali Chintagumpala, Kimberly P Raghubar

Faculty, Staff and Student Publications

OBJECTIVE: Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers lower doses of radiation to healthy brain tissue. PRT has been associated with improved long-term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory.

METHOD: Survivors of pediatric brain tumor treated with either XRT (

RESULTS: Overall, patients receiving PRT demonstrated superior verbal learning and recall compared to those treated with XRT. Encoding and retrieval deficits were more common in the XRT group than the PRT …


Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li Feb 2023

Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li

Faculty, Staff and Student Publications

Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. …


Gene Expression Profiling Of Circulating Tumor Cells Captured By Microcavity Array Is Superior To Enumeration In Demonstrating Therapy Response In Patients With Newly Diagnosed Advanced And Locally Advanced Non-Small Cell Lung Cancer, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Pablo Lopez Bravo, Wei Qiao, Suyu Liu, Luyang Yao, Steven H Lin, James M Reuben Jan 2023

Gene Expression Profiling Of Circulating Tumor Cells Captured By Microcavity Array Is Superior To Enumeration In Demonstrating Therapy Response In Patients With Newly Diagnosed Advanced And Locally Advanced Non-Small Cell Lung Cancer, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Pablo Lopez Bravo, Wei Qiao, Suyu Liu, Luyang Yao, Steven H Lin, James M Reuben

Faculty, Staff and Student Publications

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC.

Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase …


Association Between Covid-19 And Postoperative Neurological Complications And Antipsychotic Medication Use After Cancer Surgery: A Retrospective Study, Juan P Cata, Jian Hu, Lei Feng, Caroline Chung, Scott E Woodman, Larissa A Meyer Jan 2023

Association Between Covid-19 And Postoperative Neurological Complications And Antipsychotic Medication Use After Cancer Surgery: A Retrospective Study, Juan P Cata, Jian Hu, Lei Feng, Caroline Chung, Scott E Woodman, Larissa A Meyer

Faculty, Staff and Student Publications

Introduction: Millions of Americans infected with the severe acute respiratory syndrome-associated coronavirus-19 (COVID-19) need oncologic surgery. Patients with acute or resolved COVID-19 illness complain of neuropsychiatric symptoms. How surgery affects postoperative neuropsychiatric outcomes such as delirium is unknown. We hypothesize that patients with a history of COVID-19 could have an exaggerated risk of developing postoperative delirium after undergoing major elective oncologic surgery.

Methods: We conducted a retrospective study to determine the association between COVID-19 status and antipsychotic drugs during postsurgical hospitalization as a surrogate of delirium. Secondary outcomes included 30 days of postoperative complications, length of stay, and mortality. Patients …


Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira Jan 2023

Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the …


Blastoid B-Cell Neoplasms: Diagnostic Challenges And Solutions, Lianqun Qiu, Sa A Wang, Guilin Tang, Wei Wang, Pei Lin, Jie Xu, C Cameron Yin, Mahsa Khanlari, L Jeffrey Medeiros, Shaoying Li Jan 2023

Blastoid B-Cell Neoplasms: Diagnostic Challenges And Solutions, Lianqun Qiu, Sa A Wang, Guilin Tang, Wei Wang, Pei Lin, Jie Xu, C Cameron Yin, Mahsa Khanlari, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

Blastoid B-cell neoplasms mainly include B-lymphoblastic leukemia/lymphoma (B-ALL), blastoid mantle cell lymphoma, and high-grade B-cell lymphoma with blastoid morphologic features (blastoid HGBL). Distinguishing blastoid HGBL from B-ALL can be challenging and we previously developed six-point flow cytometry-focused and three-point immunohistochemistry-focused scoring systems to aid in differential diagnosis. However, the six-point scoring system was derived from bone marrow cases and occasional cases may have a misleading score using either system. In this study, we assessed 121 cases of blastoid-HGBL (37 BM and 84 extramedullary) to validate the six-point scoring system in all tissue types and to further compare the two scoring …