17,157 results match your criteria: "St. Jude Children's Research Hospital[Affiliation]"

Development of a high-throughput platform for quantitation of histone modifications on a new QTOF instrument.

Mol Cell Proteomics

December 2024

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, United States. Electronic address:

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The 5 histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry-based approaches, identification and quantification of modified histone peptides remains challenging due to factors such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks.

View Article and Find Full Text PDF

Integrating cancer into crisis: a global vision for action from WHO and partners.

Lancet Oncol

December 2024

Department of Noncommunicable Diseases, Rehabilitation and Disability, WHO, Geneva, Switzerland.

More than a billion people live in fragile, conflict-affected, and vulnerable settings requiring humanitarian support, where cancer is a substantial health issue. Despite its substantial effect on populations, cancer care remains underprioritised in emergency preparedness and response frameworks and humanitarian operational planning. This Policy Review summarises the perspectives and actionable recommendations from the First Global High-Level Technical Meeting on Non-communicable Diseases in Humanitarian Settings, with a focus on cancer.

View Article and Find Full Text PDF

Development of tetracycline analogues with increased aqueous stability for the treatment of mycobacterial infections.

Tuberculosis (Edinb)

December 2024

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS#1000, Memphis, TN, 38105, USA. Electronic address:

Tetracycline analogs from the minocycline family have recently shown promise for the treatment of non-tuberculous mycobacterial infections. However, current tetracycline and minocycline therapeutics can be limited by tolerability, stability, or inactivation by TetX. In this study, a series of novel 9-heteroaryl substituted minocycline analogs were designed and synthesized, which resulted in analogs with good in vitro activity against Mycobacterium tuberculosis and Mycobacterium abscessus, stability in water for more than 7 days, avoidance of TetX inactivation in M.

View Article and Find Full Text PDF

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients And Methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1).

View Article and Find Full Text PDF

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

View Article and Find Full Text PDF

Cracking the code of adaptive immunity: The role of computational tools.

Cell Syst

December 2024

Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address:

In recent years, the advances in high-throughput and deep sequencing have generated a diverse amount of adaptive immune repertoire data. This surge in data has seen a proportional increase in computational methods aimed to characterize T cell receptor (TCR) repertoires. In this perspective, we will provide a brief commentary on the various domains of TCR repertoire analysis, their respective computational methods, and the ongoing challenges.

View Article and Find Full Text PDF

Estimating disability prevalence in population surveys: an exploratory study using national surveys carried out in Ethiopia, Uganda, Tanzania and USA.

Disabil Rehabil

December 2024

Former Department for Information, Evidence and Research, World Health Organization, Geneva, Switzerland.

Background: The call for high quality disability data has gained momentum around the world. The objective of this paper is to analyse the consistency of estimates obtained with the Washington Group short set of questions, which are being recommended for use in national population surveys.

Methods: Prevalence rates and their 95% confidence intervals were estimated using data from five surveys carried out in three low-income countries and one high-income country.

View Article and Find Full Text PDF

The α4β2 nicotinic acetylcholine receptor (nAChR), an ionophore, has been suggested to signal through metabotropic pathways and interact with other receptor families, such as dopamine receptors. In this study, the interaction between α4β2 nAChR and dopamine receptors was investigated through in vivo and in vitro studies. Nicotine exposure in adolescent rats is known to induce a sustained increase in nicotine's rewarding effects which was assessed by conditioned place preference (CPP) assay.

View Article and Find Full Text PDF

Meeting metformin again for the first time.

Sci Adv

December 2024

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38139, USA.

New evidence convincingly shows that metformin, a drug that reduces circulating glucose, acts by inhibiting mitochondrial complex I.

View Article and Find Full Text PDF

Background: The relationships among treatment exposures, body composition, and estimated glomerular filtration rate (eGFR) in adult survivors of Wilms tumor have not been well studied.

Methods: We evaluated body composition with dual-energy x-ray absorptiometry (DXA) and eGFR with the updated Chronic Kidney Disease Epidemiology Collaboration equations (creatinine only-eGFR, cystatin C only-eGFR, creatinine and cystatin C-eGFR) without race in 134 adults previously treated for unilateral, non-syndromic Wilms tumor at St. Jude Children's Research Hospital between 1964 and 2004 with chemotherapy and with (hemiabdomen [HA] or whole abdomen [WA]) or without radiation therapy (RT).

View Article and Find Full Text PDF

Background: Pediatric immunocompromised patients are at an increased risk of severe respiratory syncytial virus (RSV) infection. Here, we aimed to describe the clinical course and outcomes of RSV infection in immunocompromised children.

Methods: This single-center study at St.

View Article and Find Full Text PDF

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

View Article and Find Full Text PDF

Nudix hydrolase 15 (NUDT15) deficiency is strongly associated with thiopurine-induced myelosuppression. Currently, testing for NUDT15 deficiency is based on the genotyping of the most frequent and clinically characterized no-function variants, that is, *2, *3 and *9. The Hispanic/Latino-predominant variant NUDT15 *4 (p.

View Article and Find Full Text PDF

Background: The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.

Methods: The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy.

View Article and Find Full Text PDF

Elucidating Sex-Specific Immune Profiles in a Breast Cancer Model.

Int J Mol Sci

December 2024

Program in Cancer Biology, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.

Breast cancer is commonly thought of as a "women's disease". However, men are increasingly diagnosed with the disease, and their mortality rates are disparately higher than those of female patients. The abundance and composition of the immune microenvironment are determinants of breast cancer progression and survival.

View Article and Find Full Text PDF

Objective: There is an ongoing debate regarding the optimal treatment for craniosynostosis as diverse factors influence the election between endoscopic and open surgery. Previous evidence favors endoscopic procedures. However, evidence remains unfulfilled by a limited number of patients and clustered in very few centers worldwide making it difficult to define it as a replicable technique in different populations.

View Article and Find Full Text PDF

Pathology, a fundamental discipline that bridges basic scientific discovery to the clinic, is integral to successful drug development. Intrinsically multimodal and multidimensional, anatomic pathology continues to be empowered by advancements in molecular and digital technologies enabling the spatial tissue detection of biomolecules such as genes, transcripts, and proteins. Over the past two decades, breakthroughs in spatial molecular biology technologies and advancements in automation and digitization of laboratory processes have enabled the implementation of higher throughput assays and the generation of extensive molecular data sets from tissue sections in biopharmaceutical research and development research units.

View Article and Find Full Text PDF

Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder caused by haploinsufficiency of ribosomal protein genes, most commonly RPS19. Limited access to patient hematopoietic stem/progenitor cells (HSPCs) is a major roadblock to developing novel therapies for DBAS. We developed a novel self-inactivating third-generation RPS19-encoding lentiviral vector (LV), termed "SJEFS-S19", for DBAS gene therapy.

View Article and Find Full Text PDF
Article Synopsis
  • * Understanding inherited traits is essential for making decisions regarding allogeneic hematopoietic cell transplants (allo-HCT) and choosing suitable donors.
  • * The case of a 49-year-old woman with JAK2 V617F-positive primary myelofibrosis (PMF) illustrates the significance of genetic findings, including a variant in the SH2B3 gene, in clinical management and genetic counseling for transplant options.
View Article and Find Full Text PDF

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Cell Stem Cell

December 2024

Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Stem Cell Institute, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

View Article and Find Full Text PDF