Outcomes Of Patients Treated For Hepatoblastoma With Low Alpha-Fetoprotein And/Or Small Cell Undifferentiated Histology: A Report From The Children's Hepatic Tumors International Collaboration (Chic),
2023
The Texas Medical Center Library
Outcomes Of Patients Treated For Hepatoblastoma With Low Alpha-Fetoprotein And/Or Small Cell Undifferentiated Histology: A Report From The Children's Hepatic Tumors International Collaboration (Chic), Angela D Trobaugh-Lotrario, Rudolf Maibach, Daniel C Aronson, Arun Rangaswami, Beate Häberle, Allison F O'Neill, Irene Schmid, Marc Ansari, Tomoro Hishiki, Sarangarajan Ranganathan, Rita Alaggio, Ronald R De Krijger, Yukichi Tanaka, Soo-Jin Cho, Christian Vokuhl, Rebecca Maxwell, Mark Krailo, Eiso Hiyama, Piotr Czauderna, Milton Finegold, James H Feusner, Marcio H Malogolowkin, Rebecka L Meyers, Dolores Lopez-Terrada
Faculty, Staff and Students Publications
Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid …
Technology Meets Tils: Deciphering T Cell Function In The -Omics Era,
2023
The Texas Medical Center Library
Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland
Faculty, Staff and Students Publications
T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …
Feasibility And Preclinical Efficacy Of Cd7-Unedited Cd7 Car T Cells For T Cell Malignancies,
2023
The Texas Medical Center Library
Feasibility And Preclinical Efficacy Of Cd7-Unedited Cd7 Car T Cells For T Cell Malignancies, Norihiro Watanabe, Feiyan Mo, Rong Zheng, Royce Ma, Vanesa C Bray, Dayenne G Van Leeuwen, Juntima Sritabal-Ramirez, Hongxiang Hu, Sha Wang, Birju Mehta, Madhuwanti Srinivasan, Lauren D Scherer, Huimin Zhang, Sachin G Thakkar, Laquisa C Hill, Helen E Heslop, Chonghui Cheng, Malcolm K Brenner, Maksim Mamonkin
Faculty, Staff and Students Publications
Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy of blood malignancies is frequently complicated by self-targeting of CAR T cells or their excessive differentiation driven by constant CAR signaling. Expression of CARs targeting CD7, a pan-T cell antigen highly expressed in T cell malignancies and some myeloid leukemias, produces robust fratricide and often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show fratricide of CD7 CAR T cells can be fully prevented using ibrutinib and dasatinib, the pharmacologic inhibitors of key CAR/CD3ζ signaling kinases. Supplementation with ibrutinib and dasatinib rescued the …
Molecular Subtyping And Survival Analysis Of Osteosarcoma Reveals Prognostic Biomarkers And Key Canonical Pathways,
2023
University of Nebraska Medical Center
Molecular Subtyping And Survival Analysis Of Osteosarcoma Reveals Prognostic Biomarkers And Key Canonical Pathways, Siddesh Southekal, Sushil Kumar Shakyawar, Prachi Bajpai, Amr Elkholy, Upender Manne, Nitish Kumar Mishra, Chittibabu Guda
Journal Articles: Genetics, Cell Biology & Anatomy
Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. …
A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions,
2023
University of Nebraska Medical Center
A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell A. Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan
Journal Articles: Genetics, Cell Biology & Anatomy
Porous alginate (Alg) hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden Alg hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross-linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion-cross-linked Alg hydrogel. Those …
Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8,
2023
Harvard Medical School
Rescue Of Auditory Function By A Single Administration Of Aav-Tmprss3 Gene Therapy In Aged Mice Of Human Recessive Deafness Dfnb8, Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen
Journal Articles: Genetics, Cell Biology & Anatomy
Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. …
Effect Of Stretch And Release On Myofascial Stem Cell Function In Vitro: A Putative Model To Understand The Molecular Benefits Of The Myofascial Release (Mfr) Technique,
2023
Lincoln Memorial University
Effect Of Stretch And Release On Myofascial Stem Cell Function In Vitro: A Putative Model To Understand The Molecular Benefits Of The Myofascial Release (Mfr) Technique, Ben Smith, Shahn Notta, Debasis Mondal
Research Day
Despite the beneficial effects of osteopathic manipulative techniques (OMT), there is a lack of in vitro models to understand the molecular mechanisms associated with these time-tested therapies. The Myofascial Release (MFR) technique is a non-invasive approach that involves passive stretching, hold and release, of the soft tissue to achieve myofascial homeostasis. Tissue-resident mesenchymal stem cells (MSC) can regulate the myofascial microenvironment by altering their secreted factors following stretch and release. Therefore, we initiated studies to develop an in vitro model to investigate the possible effects of stretch and release on MSC function, i.e. proliferation and differentiation capabilities, and changes in …
Steady-State Regulation Of Secretory Cargo Export And Er Homeostasis By Inositol Trisphosphate Receptors And Penta-Ef-Hand Proteins,
2023
University of Montana, Missoula
Steady-State Regulation Of Secretory Cargo Export And Er Homeostasis By Inositol Trisphosphate Receptors And Penta-Ef-Hand Proteins, Aaron J. Held
Graduate Student Theses, Dissertations, & Professional Papers
Constant protein degradation and turnover necessitates constitutive secretion that delivers the correct mix of nascent proteins to their appropriate subcellular destinations. Cells thus exhibit steady-state secretion and the additional ability to adjust secretory flux, though we lack a clear understanding of this critical process. During secretion, the COPII coat is responsible for providing a balance of actively and passively selected ER cargos to enter the secretory pathway. Furthermore, Ca2+ -binding proteins have been implicated in regulating this process in response to Ca2+ signals. In Chapter 1, we review the secretory pathway and vesicular trafficking, with a focus on …
Gene Expression In Mice With Endothelium-Specific Telomerase Knockout,
2023
The Texas Medical Center Library
Gene Expression In Mice With Endothelium-Specific Telomerase Knockout, Zhanguo Gao, Yongmei Yu, Yulin Dai, Zhongming Zhao, Kristin Eckel-Mahan, Mikhail G Kolonin
Faculty, Staff and Student Publications
No abstract provided.
Heterogeneity Of Memory T Cells In Aging,
2023
The Texas Medical Center Library
Heterogeneity Of Memory T Cells In Aging, Abhinav Jain, Ines Sturmlechner, Cornelia M Weyand, Jörg J Goronzy
Faculty, Staff and Student Publications
Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in …
Protein Translation Paradox: Implications In Translational Regulation Of Aging,
2023
The Texas Medical Center Library
Protein Translation Paradox: Implications In Translational Regulation Of Aging, Harper S Kim, Andrew M Pickering
Faculty, Staff and Student Publications
Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong …
Formation Of Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9 In Human Melanoma,
2023
Virginia Commonwealth University
Formation Of Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9 In Human Melanoma, Jinkal Shah
Theses and Dissertations
Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify an alternative pathway -vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like networks, such as plasma and red blood cells. The co-generation of endothelial cells, …
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells,
2023
Virginia Commonwealth University
Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh
Undergraduate Research Posters
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …
Isoprenylation Inhibition Suppresses Fcεri-Mediated Mast Cell Function And Allergic Inflammation,
2023
Virginia Commonwealth University
Isoprenylation Inhibition Suppresses Fcεri-Mediated Mast Cell Function And Allergic Inflammation, Aditya Kotha, Jordan M. Dailey, Aslamuzzaman Kazi, Said Sebti, John J. Ryan
Undergraduate Research Posters
Allergic disease is driven by cell signaling cascades that activate immune cells. One key player is mast cells, which is activated by IgE antibodies signaling through the high affinity IgE receptor, FceRI. Therefore, targeting FceRI-mediated cascades can offer for novel treatments for allergic disease. Statins have been demonstrated to reduce the severity of asthma, a common allergic airway disease. Statins are an FDA approved class of drugs with the intended purpose of lowering blood cholesterol. We previously found that while statins inhibit mast cell function in allergic disease, these anti-inflammatory effects vary widely amongst differing mouse strains and human donors, …
Resveratrol Attenuates Staphylococcal Enterotoxin B-Activated Immune Cell Metabolism,
2023
The Texas Medical Center Library
Resveratrol Attenuates Staphylococcal Enterotoxin B-Activated Immune Cell Metabolism, Hasan Alghetaa, Amira Mohammed, Narendra Singh, Kiesha Wilson, Goushuai Cai, Nagireddy Putluri, Mitzi Nagarkatti, Prakash Nagarkatti
Faculty, Staff and Students Publications
Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. …
The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis,
2023
The Texas Medical Center Library
The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty
Faculty, Staff and Students Publications
Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …
The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth,
2023
The Texas Medical Center Library
The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert
Faculty, Staff and Students Publications
FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …
Assessment Of The Cytolytic Potential Of A Multivirus-Targeted T Cell Therapy Using A Vital Dye-Based, Flow Cytometric Assay,
2023
The Texas Medical Center Library
Assessment Of The Cytolytic Potential Of A Multivirus-Targeted T Cell Therapy Using A Vital Dye-Based, Flow Cytometric Assay, Kiriakos Koukoulias, Penelope G Papayanni, Julia Jones, Manik Kuvalekar, Ayumi Watanabe, Yovana Velazquez, Sarah Gilmore, Anastasia Papadopoulou, Ann M Leen, Spyridoula Vasileiou
Faculty, Staff and Students Publications
Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (51Cr) release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects [i.e. sensitivity, short (4-6 hours) assay duration] may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses [Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr …
Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle,
2023
The Texas Medical Center Library
Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle, Jufen Liu, Yunping Lei, Lei Wang, Chao Guo
Faculty, Staff and Students Publications
No abstract provided.
Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain,
2023
The Texas Medical Center Library
Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain, Matthew T Buckley, Eric D Sun, Benson M George, Ling Liu, Nicholas Schaum, Lucy Xu, Jaime M Reyes, Margaret A Goodell, Irving L Weissman, Tony Wyss-Coray, Thomas A Rando, Anne Brunet
Faculty, Staff and Students Publications
The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic …
