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Articles 5611 - 5640 of 14307

Full-Text Articles in Medicine and Health Sciences

Oncogenic Kras Drives Lipofibrogenesis To Promote Angiogenesis And Colon Cancer Progression, Wen-Hao Hsu, Kyle A Labella, Yiyun Lin, Ping Xu, Rumi Lee, Cheng-En Hsieh, Lei Yang, Ashley Zhou, Jonathan M Blecher, Chang-Jiun Wu, Kangyu Lin, Xiaoying Shang, Shan Jiang, Denise J Spring, Yan Xia, Peiwen Chen, John Paul Shen, Scott Kopetz, Ronald A Depinho Dec 2023

Oncogenic Kras Drives Lipofibrogenesis To Promote Angiogenesis And Colon Cancer Progression, Wen-Hao Hsu, Kyle A Labella, Yiyun Lin, Ping Xu, Rumi Lee, Cheng-En Hsieh, Lei Yang, Ashley Zhou, Jonathan M Blecher, Chang-Jiun Wu, Kangyu Lin, Xiaoying Shang, Shan Jiang, Denise J Spring, Yan Xia, Peiwen Chen, John Paul Shen, Scott Kopetz, Ronald A Depinho

Faculty, Staff and Student Publications

Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. …


Formate Supplementation Enhances Antitumor Cd8+ T-Cell Fitness And Efficacy Of Pd-1 Blockade, Jared H Rowe, Ilaria Elia, Osmaan Shahid, Emily F Gaudiano, Natalia E Sifnugel, Sheila Johnson, Amy G Reynolds, Megan E Fung, Shakchhi Joshi, Martin W Lafleur, Joon Seok Park, Kristen E Pauken, Joshua D Rabinowitz, Gordon J Freeman, Marcia C Haigis, Arlene H Sharpe Dec 2023

Formate Supplementation Enhances Antitumor Cd8+ T-Cell Fitness And Efficacy Of Pd-1 Blockade, Jared H Rowe, Ilaria Elia, Osmaan Shahid, Emily F Gaudiano, Natalia E Sifnugel, Sheila Johnson, Amy G Reynolds, Megan E Fung, Shakchhi Joshi, Martin W Lafleur, Joon Seok Park, Kristen E Pauken, Joshua D Rabinowitz, Gordon J Freeman, Marcia C Haigis, Arlene H Sharpe

Faculty, Staff and Student Publications

UNLABELLED: The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for …


Bringing Car T Cell Therapy Trials To Underserved Populations, Hoda Badr, Rayne Rouce, Michael E Scheurer, Premal Lulla, Martha Mims, Pavan Reddy Dec 2023

Bringing Car T Cell Therapy Trials To Underserved Populations, Hoda Badr, Rayne Rouce, Michael E Scheurer, Premal Lulla, Martha Mims, Pavan Reddy

Faculty, Staff and Students Publications

There is a critical need for equitable access to cell therapies in cancer treatment, particularly within public safety-net healthcare systems that serve minority and socioeconomically disadvantaged populations. We discuss how the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine is piloting a cell therapy program aimed at addressing cancer care disparities and has the potential to serve as a national model for enhancing health equity in cancer care.


Labour Market Participation After Sickness Absence Due To Cancer: A Dynamic Cohort Study In Catalonia (Spain), Amaya Ayala-Garcia, Fernando G Benavides, Laura Serra Dec 2023

Labour Market Participation After Sickness Absence Due To Cancer: A Dynamic Cohort Study In Catalonia (Spain), Amaya Ayala-Garcia, Fernando G Benavides, Laura Serra

Faculty, Staff and Student Publications

BACKGROUND: The consequences of cancer on working until retirement age remain unclear. This study aimed to analyse working life considering all possible labour market states in a sample of workers after sickness absence (SA) due to cancer and to compare their working life paths to those of a sample of workers without SA and with an SA due to other diseases.

METHODS: This was a retrospective dynamic cohort study among social security affiliates in Catalonia from 2012-2018. Cases consisted of workers with an SA due to cancer between 2012-2015 (N = 516) and were individually age- and sex-matched with those …


A Phase I Trial Of Bevacizumab And Temsirolimus In Combination With Valproic Acid In Advanced Solid Tumors, Blessie Elizabeth Nelson, Apostolia M Tsimberidou, Xueyao Fu, Siqing Fu, Vivek Subbiah, Anil K Sood, Jordi Rodon, Daniel D Karp, George Blumenschein, Scott Kopetz, Shubham Pant, Sarina A Piha-Paul Dec 2023

A Phase I Trial Of Bevacizumab And Temsirolimus In Combination With Valproic Acid In Advanced Solid Tumors, Blessie Elizabeth Nelson, Apostolia M Tsimberidou, Xueyao Fu, Siqing Fu, Vivek Subbiah, Anil K Sood, Jordi Rodon, Daniel D Karp, George Blumenschein, Scott Kopetz, Shubham Pant, Sarina A Piha-Paul

Faculty, Staff and Student Publications

BACKGROUND: Preclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity.

METHODS: This phase I study enrolled 47 patients between April 2012 and 2018 and determined safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) when combining bevacizumab, temsirolimus, and valproic acid in patients with advanced cancer.

RESULTS: Median age of enrolled patients was 56 years. Patients were heavily pretreated with a median of 4 lines of prior therapy. Forty-five patients (95.7%) experienced one or more treatment-related adverse events (TRAEs). Grade 3 TRAEs were lymphopenia (14.9%), thrombocytopenia (8.5%), and mucositis …


Taxane-Based Chemotherapy Is Effective In Metastatic Appendiceal Adenocarcinoma, Julia Dansby, Aditya More, Mohammad Zeineddine, Abdelrahman Yousef, Alisha Bent, Farshid Dayyani, Robert Wolff, Michael Overman, John Paul Shen Dec 2023

Taxane-Based Chemotherapy Is Effective In Metastatic Appendiceal Adenocarcinoma, Julia Dansby, Aditya More, Mohammad Zeineddine, Abdelrahman Yousef, Alisha Bent, Farshid Dayyani, Robert Wolff, Michael Overman, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study …


Sustained Disease Control In Immune Checkpoint Blockade Responders With Microsatellite Instability-High Colorectal Cancer After Treatment Termination, Kristen Simmons, Jane V Thomas, Kaysia Ludford, Jason A Willis, Victoria S Higbie, Kanwal P S Raghav, Benny Johnson, Arvind Dasari, Bryan K Kee, Christine M Parseghian, Michael S Lee, Phat H Le, Maria P Morelli, John Paul Shen, Alisha Bent, Eduardo Vilar, Robert A Wolff, Scott Kopetz, Michael J Overman, Van Karlyle Morris Dec 2023

Sustained Disease Control In Immune Checkpoint Blockade Responders With Microsatellite Instability-High Colorectal Cancer After Treatment Termination, Kristen Simmons, Jane V Thomas, Kaysia Ludford, Jason A Willis, Victoria S Higbie, Kanwal P S Raghav, Benny Johnson, Arvind Dasari, Bryan K Kee, Christine M Parseghian, Michael S Lee, Phat H Le, Maria P Morelli, John Paul Shen, Alisha Bent, Eduardo Vilar, Robert A Wolff, Scott Kopetz, Michael J Overman, Van Karlyle Morris

Faculty, Staff and Student Publications

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior …


Spatiotemporal Genomic Profiling Of Intestinal Metaplasia Reveals Clonal Dynamics Of Gastric Cancer Progression, Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan, Singapore Gastric Cancer Consortium Dec 2023

Spatiotemporal Genomic Profiling Of Intestinal Metaplasia Reveals Clonal Dynamics Of Gastric Cancer Progression, Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan, Singapore Gastric Cancer Consortium

Faculty, Staff and Student Publications

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy …


1756 Evaluating The Impact Of Prophylactic Intrathecal Chemotherapy In Diffuse Large B Cell Lymphoma (Dlbcl) Patients With High Central Nervous System International Prognostic Index (Cns-Ipi) Scores: A Comprehensive Review And Meta-Analysis, Kadhim Al-Banaa, Alfarooq Alshaikhli, Shyam Poudel, Shiva Shrotria, Can Wang, Paul Hanona, Swathi Gopishetty, Precious Idogun, Daniel Ezekwudo, Ishmael Jaiyesimi Dec 2023

1756 Evaluating The Impact Of Prophylactic Intrathecal Chemotherapy In Diffuse Large B Cell Lymphoma (Dlbcl) Patients With High Central Nervous System International Prognostic Index (Cns-Ipi) Scores: A Comprehensive Review And Meta-Analysis, Kadhim Al-Banaa, Alfarooq Alshaikhli, Shyam Poudel, Shiva Shrotria, Can Wang, Paul Hanona, Swathi Gopishetty, Precious Idogun, Daniel Ezekwudo, Ishmael Jaiyesimi

Conference Presentation Abstracts

No abstract provided.


Fully-Automated, Ct-Only Gtv Contouring For Palliative Head And Neck Radiotherapy, Skylar S Gay, Carlos E Cardenas, Callistus Nguyen, Tucker J Netherton, Cenji Yu, Yao Zhao, Stephen Skett, Tina Patel, Delali Adjogatse, Teresa Guerrero Urbano, Komeela Naidoo, Beth M Beadle, Jinzhong Yang, Ajay Aggarwal, Laurence E Court Dec 2023

Fully-Automated, Ct-Only Gtv Contouring For Palliative Head And Neck Radiotherapy, Skylar S Gay, Carlos E Cardenas, Callistus Nguyen, Tucker J Netherton, Cenji Yu, Yao Zhao, Stephen Skett, Tina Patel, Delali Adjogatse, Teresa Guerrero Urbano, Komeela Naidoo, Beth M Beadle, Jinzhong Yang, Ajay Aggarwal, Laurence E Court

Faculty, Staff and Student Publications

Planning for palliative radiotherapy is performed without the advantage of MR or PET imaging in many clinics. Here, we investigated CT-only GTV delineation for palliative treatment of head and neck cancer. Two multi-institutional datasets of palliative-intent treatment plans were retrospectively acquired: a set of 102 non-contrast-enhanced CTs and a set of 96 contrast-enhanced CTs. The nnU-Net auto-segmentation network was chosen for its strength in medical image segmentation, and five approaches separately trained: (1) heuristic-cropped, non-contrast images with a single GTV channel, (2) cropping around a manually-placed point in the tumor center for non-contrast images with a single GTV channel, (3) …


Evaluating Clinical Outcomes In Patients Being Treated Exclusively Via Telepsychiatry: Retrospective Data Analysis, Cheryl Person, Nicola O'Connor, Lucy Koehler, Kartik Venkatachalam, Georgia Gaveras Dec 2023

Evaluating Clinical Outcomes In Patients Being Treated Exclusively Via Telepsychiatry: Retrospective Data Analysis, Cheryl Person, Nicola O'Connor, Lucy Koehler, Kartik Venkatachalam, Georgia Gaveras

Faculty, Staff and Student Publications

BACKGROUND: Depression and anxiety are highly prevalent conditions in the United States. Despite the availability of suitable therapeutic options, limited access to high-quality psychiatrists represents a major barrier to treatment. Although telepsychiatry has the potential to improve access to psychiatrists, treatment efficacy in the telepsychiatry model remains unclear.

OBJECTIVE: Our primary objective was to determine whether there was a clinically meaningful change in 1 of 2 validated outcome measures of depression and anxiety-the Patient Health Questionnaire-8 (PHQ-8) or the Generalized Anxiety Disorder-7 (GAD-7)-after receiving at least 8 weeks of treatment in an outpatient telepsychiatry setting.

METHODS: We included treatment-seeking patients …


Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot Dec 2023

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …


Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren Dec 2023

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …


Optical Genome Mapping Helps To Identify Bcr::Jak2 Rearrangement Arising From Cryptic Complex Chromosomal Aberrations: A Case Report And Literature Review, Neelam Vanjari, Guilin Tang, Gokce A Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J Dave, Joseph D Khoury, L Jeffrey Medeiros, Zhenya Tang Dec 2023

Optical Genome Mapping Helps To Identify Bcr::Jak2 Rearrangement Arising From Cryptic Complex Chromosomal Aberrations: A Case Report And Literature Review, Neelam Vanjari, Guilin Tang, Gokce A Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J Dave, Joseph D Khoury, L Jeffrey Medeiros, Zhenya Tang

Faculty, Staff and Student Publications

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical …


Rad54l2-Mediated Dna Damage Avoidance Pathway Specifically Preserves Genome Integrity In Response To Topoisomerase 2 Poisons, Huimin Zhang, Yun Xiong, Yilun Sun, Jeong-Min Park, Dan Su, Xu Feng, Sarah Keast, Mengfan Tang, Min Huang, Chao Wang, Mrinal Srivastava, Chang Yang, Dandan Zhu, Zhen Chen, Siting Li, Ling Yin, Yves Pommier, Junjie Chen Dec 2023

Rad54l2-Mediated Dna Damage Avoidance Pathway Specifically Preserves Genome Integrity In Response To Topoisomerase 2 Poisons, Huimin Zhang, Yun Xiong, Yilun Sun, Jeong-Min Park, Dan Su, Xu Feng, Sarah Keast, Mengfan Tang, Min Huang, Chao Wang, Mrinal Srivastava, Chang Yang, Dandan Zhu, Zhen Chen, Siting Li, Ling Yin, Yves Pommier, Junjie Chen

Faculty, Staff and Student Publications

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted …


The Defined Tlr3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy And Potentiates Anti-Pd-1 Antibody Therapy By Enhancing Immune Cell Infiltration, Seung-Hwan Lee, Young-Ho Choi, Soon Myung Kang, Min-Gyu Lee, Arnaud Debin, Eric Perouzel, Seung-Beom Hong, Dong-Ho Kim Dec 2023

The Defined Tlr3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy And Potentiates Anti-Pd-1 Antibody Therapy By Enhancing Immune Cell Infiltration, Seung-Hwan Lee, Young-Ho Choi, Soon Myung Kang, Min-Gyu Lee, Arnaud Debin, Eric Perouzel, Seung-Beom Hong, Dong-Ho Kim

Faculty, Staff and Student Publications

Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 …


Phenotyping Emt And Met Cellular States In Lung Cancer Patient Liquid Biopsies At A Personalized Level Using Mass Cytometry, Loukia G Karacosta, Danny Pancirer, Jordan S Preiss, Jalen A Benson, Winston Trope, Joseph B Shrager, Arthur Wai Sung, Joel W Neal, Sean C Bendall, Heather Wakelee, Sylvia K Plevritis Dec 2023

Phenotyping Emt And Met Cellular States In Lung Cancer Patient Liquid Biopsies At A Personalized Level Using Mass Cytometry, Loukia G Karacosta, Danny Pancirer, Jordan S Preiss, Jalen A Benson, Winston Trope, Joseph B Shrager, Arthur Wai Sung, Joel W Neal, Sean C Bendall, Heather Wakelee, Sylvia K Plevritis

Faculty, Staff and Student Publications

Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT-MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ …


Ewsr1::Atf1 Orchestrates The Clear Cell Sarcoma Transcriptome In Human Tumors And A Mouse Genetic Model, Benjamin B Ozenberger, Li Li, Emily R Wilson, Alexander J Lazar, Jared J Barrott, Kevin B Jones Dec 2023

Ewsr1::Atf1 Orchestrates The Clear Cell Sarcoma Transcriptome In Human Tumors And A Mouse Genetic Model, Benjamin B Ozenberger, Li Li, Emily R Wilson, Alexander J Lazar, Jared J Barrott, Kevin B Jones

Faculty, Staff and Student Publications

Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1. The EWSR1::ATF1 fusion oncoprotein reprograms transcription. However, the binding distribution of EWSR1::ATF1 across the genome and its target genes remain unclear. Here, we interrogated the genomic distribution of V5-tagged EWSR1::ATF1 in tumors it had induced upon expression in mice that also recapitulated the transcriptome of human CCS. ChIP-sequencing of V5-EWSR1::ATF1 identified previously unreported motifs …


Lessons Learnt In The First Year Of An Australian Pediatric Cardio Oncology Clinic., Claudia Toro, Ben Felmingham, Mangesh Jhadav, David S. Celermajer, Andre La Gerche, John O'Sullivan, Sanjeev Kumar, Marion K. Mateos, Joy M. Fulbright, Dinisha Govender, Lane Collier, Michael Cheung, David D. Eisenstat, Peter W. Lange, Julian Ayer, David A. Elliott, Rachel Conyers Dec 2023

Lessons Learnt In The First Year Of An Australian Pediatric Cardio Oncology Clinic., Claudia Toro, Ben Felmingham, Mangesh Jhadav, David S. Celermajer, Andre La Gerche, John O'Sullivan, Sanjeev Kumar, Marion K. Mateos, Joy M. Fulbright, Dinisha Govender, Lane Collier, Michael Cheung, David D. Eisenstat, Peter W. Lange, Julian Ayer, David A. Elliott, Rachel Conyers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management.

OBJECTIVES: Our pediatric cardio-oncology clinic aimed to: (i) Document cardiovascular toxicities observed within a pediatric cardio-oncology clinic and. (ii) Evaluate the applicability of the Australian and New Zealand Pediatric …


Archery: A Prospective Observational Study Of Artificial Intelligence-Based Radiotherapy Treatment Planning For Cervical, Head And Neck And Prostate Cancer – Study Protocol, Ajay Aggarwal, Laurence Edward Court, Peter Hoskin, Isabella Jacques, Mariana Kroiss, Sarbani Laskar, Yolande Lievens, Indranil Mallick, Rozita Abdul Malik, Elizabeth Miles, Issa Mohamad, Claire Murphy, Matthew Nankivell, Jeannette Parkes, Mahesh Parmar, Carol Roach, Hannah Simonds, Julie Torode, Barbara Vanderstraeten, Ruth Langley Dec 2023

Archery: A Prospective Observational Study Of Artificial Intelligence-Based Radiotherapy Treatment Planning For Cervical, Head And Neck And Prostate Cancer – Study Protocol, Ajay Aggarwal, Laurence Edward Court, Peter Hoskin, Isabella Jacques, Mariana Kroiss, Sarbani Laskar, Yolande Lievens, Indranil Mallick, Rozita Abdul Malik, Elizabeth Miles, Issa Mohamad, Claire Murphy, Matthew Nankivell, Jeannette Parkes, Mahesh Parmar, Carol Roach, Hannah Simonds, Julie Torode, Barbara Vanderstraeten, Ruth Langley

Faculty, Staff and Student Publications

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. …


The Classification Of Obesity Based On Metabolic Status Redefines The Readmission Of Non-Hodgkin’S Lymphoma-An Observational Study, Hang Dong, Honglin Guo, Jing Du, Yiping Cheng, Dawei Wang, Junming Han, Zinuo Yuan, Zhenyu Yao, Ran An, Xiaoqin Wu, Kyle L Poulsen, Zhixiang Wang, Shanshan Shao, Xiude Fan, Zhen Wang, Jiajun Zhao Dec 2023

The Classification Of Obesity Based On Metabolic Status Redefines The Readmission Of Non-Hodgkin’S Lymphoma-An Observational Study, Hang Dong, Honglin Guo, Jing Du, Yiping Cheng, Dawei Wang, Junming Han, Zinuo Yuan, Zhenyu Yao, Ran An, Xiaoqin Wu, Kyle L Poulsen, Zhixiang Wang, Shanshan Shao, Xiude Fan, Zhen Wang, Jiajun Zhao

Faculty, Staff and Student Publications

Background: The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL.

Methods: In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically …


Deep Learning-Enabled Breast Cancer Endocrine Response Determination From H&E Staining Based On Esr1 Signaling Activity, Chun Wai Ng, Kwong-Kwok Wong Dec 2023

Deep Learning-Enabled Breast Cancer Endocrine Response Determination From H&E Staining Based On Esr1 Signaling Activity, Chun Wai Ng, Kwong-Kwok Wong

Faculty, Staff and Student Publications

Estrogen receptor (ER) positivity by immunohistochemistry has long been a main selection criterium for breast cancer patients to be treated with endocrine therapy. However, ER positivity might not directly correlate with activated ER signaling activity, which is a better predictor for endocrine therapy responsiveness. In this study, we investigated if a deep learning method using whole-slide H&E-stained images could predict ER signaling activity. First, ER signaling activity score was determined using RNAseq data available from each of the 1082 breast cancer samples in the TCGA Pan-Cancer dataset based on the Hallmark Estrogen Response Early gene set from the Molecular Signature …


Patient And Physician Perspectives On Treatments For Low-Risk Prostate Cancer: A Qualitative Study, Alice Guan, Eduardo J Santiago-Rodríguez, Benjamin I Chung, Janet K Shim, Laura Allen, Mei-Chin Kuo, Kathie Lau, Zinnia Loya, James D Brooks, Iona Cheng, Mindy C Derouen, Dominick L Frosch, Todd Golden, John T Leppert, Daphne Y Lichtensztajn, Qian Lu, Debora Oh, Weiva Sieh, Michelle Wadhwa, Matthew R Cooperberg, Peter R Carroll, Scarlett L Gomez, Salma Shariff-Marco Dec 2023

Patient And Physician Perspectives On Treatments For Low-Risk Prostate Cancer: A Qualitative Study, Alice Guan, Eduardo J Santiago-Rodríguez, Benjamin I Chung, Janet K Shim, Laura Allen, Mei-Chin Kuo, Kathie Lau, Zinnia Loya, James D Brooks, Iona Cheng, Mindy C Derouen, Dominick L Frosch, Todd Golden, John T Leppert, Daphne Y Lichtensztajn, Qian Lu, Debora Oh, Weiva Sieh, Michelle Wadhwa, Matthew R Cooperberg, Peter R Carroll, Scarlett L Gomez, Salma Shariff-Marco

Faculty, Staff and Student Publications

BACKGROUND: Patients diagnosed with low-risk prostate cancer (PCa) are confronted with a difficult decision regarding whether to undergo definitive treatment or to pursue an active surveillance protocol. This is potentially further complicated by the possibility that patients and physicians may place different value on factors that influence this decision. We conducted a qualitative investigation to better understand patient and physician perceptions of factors influencing treatment decisions for low-risk PCa.

METHODS: Semi-structured interviews were conducted among 43 racially and ethnically diverse patients diagnosed with low-risk PCa, who were identified through a population-based cancer registry, and 15 physicians who were selected to …


Palliative Care Referral Protocol: Best Practice Toolkit For Improving Early Referral Rate For Adult Cancer Patients, Linda Dinh Nguyen Dec 2023

Palliative Care Referral Protocol: Best Practice Toolkit For Improving Early Referral Rate For Adult Cancer Patients, Linda Dinh Nguyen

Student Scholarly Projects

Despite the benefits of palliative care being well-documented in studies and early palliative care services being strongly recommended by reputable organizations, such as the American Society of Clinical Oncology, many patients did not receive or received late referrals (Pigni et al., 2022). This mainly occurs because oncologists commonly base their referrals on perceived needs and clinical judgment (Smith et al., 2017). Thus, this program development project aimed to create a toolkit to improve early identification and referral to palliative care for adult patients who would benefit from palliative care services. The PICO question that guides this program is: In ambulatory …


Cytogenetic Profile In Monoclonal Gammopathy Of Undetermined Significance, Smoldering And Symptomatic Multiple Myeloma: A Study Of 1087 Patients With Highly Purified Plasma Cells, Guilin Tang, Yilin Wu, Pei Lin, Gokce A Toruner, Shimin Hu, Shaoying Li, Muzaffar H Qazilbash, Robert Z Orlowski, Christine Ye, Jie Xu, Karen A Nahmod, L Jeffrey Medeiros, Zhenya Tang Dec 2023

Cytogenetic Profile In Monoclonal Gammopathy Of Undetermined Significance, Smoldering And Symptomatic Multiple Myeloma: A Study Of 1087 Patients With Highly Purified Plasma Cells, Guilin Tang, Yilin Wu, Pei Lin, Gokce A Toruner, Shimin Hu, Shaoying Li, Muzaffar H Qazilbash, Robert Z Orlowski, Christine Ye, Jie Xu, Karen A Nahmod, L Jeffrey Medeiros, Zhenya Tang

Faculty, Staff and Student Publications

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of …


Randomized Phase Ii Trial Of Dendritic Cell/Myeloma Fusion Vaccine With Lenalidomide Maintenance After Upfront Autologous Hematopoietic Cell Transplantation For Multiple Myeloma: Bmt Ctn 1401., David J Chung, Nina Shah, Juan Wu, Brent Logan, Lina Bisharat, Natalie Callander, Giulia Cheloni, Kenneth Anderson, Thinle Chodon, Binod Dhakal, Steve Devine, Poorvi Somaiya Dutt, Yvonne Efebera, Nancy Geller, Haider Ghiasuddin, Peiman Hematti, Leona Holmberg, Alan Howard, Bryon Johnson, Dimitra Karagkouni, Hillard M Lazarus, Ehsan Malek, Philip Mccarthy, David Mckenna, Adam Mendizabal, Ajay Nooka, Nikhil Munshi, Lynn O'Donnell, Aaron P Rapoport, Jane Reese, Jacalyn Rosenblatt, Robert Soiffer, Dina Stroopinsky, Lynne Uhl, Ioannis S Vlachos, Edmund K Waller, James W Young, Marcelo C Pasquini, David Avigan Dec 2023

Randomized Phase Ii Trial Of Dendritic Cell/Myeloma Fusion Vaccine With Lenalidomide Maintenance After Upfront Autologous Hematopoietic Cell Transplantation For Multiple Myeloma: Bmt Ctn 1401., David J Chung, Nina Shah, Juan Wu, Brent Logan, Lina Bisharat, Natalie Callander, Giulia Cheloni, Kenneth Anderson, Thinle Chodon, Binod Dhakal, Steve Devine, Poorvi Somaiya Dutt, Yvonne Efebera, Nancy Geller, Haider Ghiasuddin, Peiman Hematti, Leona Holmberg, Alan Howard, Bryon Johnson, Dimitra Karagkouni, Hillard M Lazarus, Ehsan Malek, Philip Mccarthy, David Mckenna, Adam Mendizabal, Ajay Nooka, Nikhil Munshi, Lynn O'Donnell, Aaron P Rapoport, Jane Reese, Jacalyn Rosenblatt, Robert Soiffer, Dina Stroopinsky, Lynne Uhl, Ioannis S Vlachos, Edmund K Waller, James W Young, Marcelo C Pasquini, David Avigan

Oncology Articles

PURPOSE: Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma-reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT).

PATIENTS AND METHODS: In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma-specific immunity at 1-year posttransplant.

RESULTS: The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients. At …


Communication With Physicians And Family About Breast Cancer Recurrence, Kimberly M. Kelly, Pragya Rai, Jamie L. Studts, Stephanie Dickinson, Beate Henschel, Mark Dignan, Mara D. Chambers, Hannah Hazard-Jenkins Dec 2023

Communication With Physicians And Family About Breast Cancer Recurrence, Kimberly M. Kelly, Pragya Rai, Jamie L. Studts, Stephanie Dickinson, Beate Henschel, Mark Dignan, Mara D. Chambers, Hannah Hazard-Jenkins

UK CARES Faculty Publications

Objective: Adequate physician-patient communication about cancer recurrence is vital to quality of life and to informed decision-making related to survivorship care. The current study was guided by a cognitive-affective framework to examine communication with family and physicians about breast cancer recurrence risk.

Methods: A survey of recently-diagnosed, early-stage breast cancer patients in Appalachia investigated physician- patient and familial communication about breast cancer recurrence risk.

Results: Over 30% of participants reported not talking to family or physicians about breast cancer recurrence risk. Younger patients reported more conversations, and speaking with physicians was associated with greater perception risk factors associated with recurrence …


Cancer Disparities In Southeast Asia: Intersectionality And A Call To Action, Erin Jay G. Feliciano, Frances Dominique V. Ho, Kaisin Yee, Joseph A. Paguio, Michelle Ann B. Eala, Janine Patricia G. Robredo, Kenrick Ng, Jasmine Lim, Khin Thuzar Pyone, Catherine A. Peralta, Jerickson Abbie Flores, J. Seth Yao, Patricia Mae G. Santos, Christian Daniel U. Ang, Gideon Lasco, Jeffrey Shi Kai Chan, Gary Tse, Enrico D. Tangco, T. Peter Kingham, Imjai Chitapanarux, Nirmala Bhoo-Pathy, Gerardo D. Legaspi, Edward Christopher Dee Dec 2023

Cancer Disparities In Southeast Asia: Intersectionality And A Call To Action, Erin Jay G. Feliciano, Frances Dominique V. Ho, Kaisin Yee, Joseph A. Paguio, Michelle Ann B. Eala, Janine Patricia G. Robredo, Kenrick Ng, Jasmine Lim, Khin Thuzar Pyone, Catherine A. Peralta, Jerickson Abbie Flores, J. Seth Yao, Patricia Mae G. Santos, Christian Daniel U. Ang, Gideon Lasco, Jeffrey Shi Kai Chan, Gary Tse, Enrico D. Tangco, T. Peter Kingham, Imjai Chitapanarux, Nirmala Bhoo-Pathy, Gerardo D. Legaspi, Edward Christopher Dee

Ateneo School of Medicine and Public Health Publications

No abstract provided.


Morphological And Metabolic Criteria Of Covid-19 Vaccine Associated Axillary Nodes On 18-Fluorodeouxyglucose Pet/Ct Imaging In Breast Cancer Patients, Nosheen Fatima, Unaiza Zaman, Areeba Zaman, Sidra Zaman, Rabia Tehseen, Maseeh Uz Zaman Dec 2023

Morphological And Metabolic Criteria Of Covid-19 Vaccine Associated Axillary Nodes On 18-Fluorodeouxyglucose Pet/Ct Imaging In Breast Cancer Patients, Nosheen Fatima, Unaiza Zaman, Areeba Zaman, Sidra Zaman, Rabia Tehseen, Maseeh Uz Zaman

Department of Radiology

Background: In the current era vaccine-associated lymphadenopathy (VAL) is not an uncommon presentation on 18F-FDG PET/CT examinations in patients inoculated with Coronavirus disease 2019 (COVID-19) vaccination. In this study, we are presenting data of VAL on 18F-FDG PET/CT regarding its prevalence, temporal response to vaccination and imaging characteristics of VAL.
Methods: Seventy-eight (78) consecutive vaccinated breast cancer (BC) patients who had 18FDG PET/CT were retrospectively analyzed. All patients had COVID-19 vaccine shots in contralateral arms and none in breast cancer site axilla (BSA). In 35 patients 18FDG avid nodes were found in vaccine site axilla (VSA). In 25 patients 18FDG …


A Gold-Based Inhibitor Of Oxidative Phosphorylation Is Effective Against Triple Negative Breast Cancer, R. Tyler Mertens, Jong Hyun Kim, Samuel Ofori, Chibuzor Ngozi Olelewe, Paul J. Kamitsuka, Gunnar F. Kwakye, Samuel G. Awuah Dec 2023

A Gold-Based Inhibitor Of Oxidative Phosphorylation Is Effective Against Triple Negative Breast Cancer, R. Tyler Mertens, Jong Hyun Kim, Samuel Ofori, Chibuzor Ngozi Olelewe, Paul J. Kamitsuka, Gunnar F. Kwakye, Samuel G. Awuah

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mito- chondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its thera- peutic potential following systemic …