A5047774479- Chemotherapy-induced organ toxicity mitigation
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Prenatal Screening and Diagnostics
- Metal complexes synthesis and properties
- Statistical Methods in Clinical Trials
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Ovarian cancer diagnosis and treatment
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Chemical Synthesis and Characterization
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Click Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Chemical Reactions and Isotopes
- Renal and related cancers
- Cancer Immunotherapy and Biomarkers
- Genomic variations and chromosomal abnormalities
- Cell death mechanisms and regulation
- Cancer Treatment and Pharmacology
- Cancer Mechanisms and Therapy
- Synthesis and biological activity
- RNA and protein synthesis mechanisms
National Cancer Institute
2023-2025
National Institutes of Health
2014-2025
Center for Cancer Research
2024-2025
University of Cambridge
2014-2024
Office of the Director
2024
Leidos (United States)
2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2024
National Human Genome Research Institute
2024
Cancer Research UK Cambridge Center
2017-2023
National Center for Advancing Translational Sciences
2014-2023
Significance The treatment of cancer is highly reliant on drug combinations. Next-generation, targeted therapeutics are demonstrating interesting single-agent activities in clinical trials; however, the discovery companion drugs through iterative trial-and-error not a tenable mechanism to prioritize clinically important combinations for these agents. Herein we describe results large, high-throughput combination screen Bruton’s tyrosine kinase inhibitor ibrutinib versus library nearly 500...
Abstract The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic as a consequence extensively studied laboratory setting. In this study, we examined literature found significant number of studies (11%–34%) prominent cancer journals utilizing cisplatin dissolved DMSO. However, dissolving DMSO for laboratory-based results ligand displacement changes to structure complex. We effect on complexes, including oxaliplatin, finding that reacted with inhibited...
We developed a series of ligand-inducible riboswitches that control gene expression in diverse species Gram-negative and Gram-positive bacteria, including human pathogens have few or no previously reported inducible systems. anticipate these will be useful tools for genetic studies wide range bacteria.
Abstract In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there instances where the marked presence of more than one point inflection, or combined agonist and antagonist effects, prevents straight-forward modelling data via standard equation. Here we propose modified model automated fitting procedure to describe with multiphasic features. The resulting general...
BackgroundCell-free DNA (cfDNA) sequence analysis to screen for fetal aneuploidy can incidentally detect maternal cancer. Additional data are needed identify DNA-sequencing patterns and other biomarkers that pregnant persons who most likely have cancer determine the best approach follow-up.MethodsIn this ongoing study we performed screening in or postpartum did not perceive signs symptoms of but received unusual clinical cfDNA-sequencing results were nonreportable (i.e., status could be...
Disease recurrence is the major cause of morbidity and mortality ovarian cancer (OC). In terms maintenance therapies after platinum-based chemotherapy, PARP inhibitors significantly improve overall survival patients with BRCA mutations but little benefit to without homologous recombination deficiency (HRD). The stem-like tumor-initiating cell (TIC) population within OC tumors are thought contribute disease chemoresistance. Therefore, there a need identify drugs that target TICs prevent...
Significance We describe a genomic disorder that causes obesity, intellectual disability, and seizures. Children with this syndrome carry an unbalanced chromosome translocation results in the duplication of over 100 genes, including G protein β3 ( GNB3 ). Although polymorphisms have been associated hypertension, diabetes, mechanism pathogenesis is unknown. created transgenic mouse model carries , weighs significantly more than wild-type mice, has excess abdominal fat. highly expressed brain...
Abstract The discovery of chemotherapeutic agents for the treatment cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer often fail to advance during clinical development, most likely because these do not reproduce cellular complexity tumors and their microenvironment vivo . use three-dimensional (3D) systems have been explored enabling more predictive vitro tumor models drug discovery. To date,...
Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment patients with metastatic cancer, but responses can be either short lived or incompletely effective. Oncogene augment the therapy, mechanisms by which these two interventions might cooperate are resolved. Using a novel transplantable BRAF(V600E)-mutant murine melanoma model (SB-3123), we explored potential synergy between selective BRAF(V600E) inhibitor vemurafenib adoptive cell...
The dynamic of cancer is intimately linked to a dysregulation the cell cycle and signalling pathways. It has been argued that selectivity treatments could exploit loss checkpoint function in cells, concept termed "cyclotherapy". Quantitative approaches describe these dysregulations can provide guidance design novel or existing therapies. We illustrate this strategy via mathematical model includes descriptions G1-S spindle assembly (SAC), EGF pathway apoptosis. incorporated sites action four...
// Marianne K. Kim 1 , Dong J. Min 2 George Wright 3 Ian Goldlust 4 Christina M. Annunziata Women's Malignancies Branch, Center for Cancer Research, National Institute, Bethesda, MD 20892 Transgenic Oncogenic and Genomics Section, Biometrics Research NIH Chemical Center, Division of Preclinical Innovation, Advancing Translational Sciences, Correspondence to: Annunziata, e-mail: annunzic@mail.nih.gov Keywords: shRNAs, therapeutic targets, IKKε, CHEK1, p21, ovarian cancer Received: October 02,...
Cell line models for high grade serous ovarian cancer (HGSOC) are limited in number and poorly clinically annotated. Consequently, existing often fail to recapitulate common features of HGSOC, inhibiting mechanistic therapeutic discovery. We generated characterised three spontaneously immortalized continuous HGSOC cell lines named CIOV1, CIOV2, CIOV3 confirmed that each retained the genomic pathologic characteristics its parental tumour. show subclonal populations present at initiation,...
Quality control (QC) metrics are critical in high throughput screening (HTS) platforms to ensure reliability and confidence assay data downstream analyses. Most reported HTS QC designed for plate level or single well analysis. With the advent of combination there is a need that quantify quality response matrices. We introduce predictive, interpretable, matrix-level metric, mQC, based on mix data-derived heuristic features. mQC accurately reproduces expert assessment correctly identifies...
Inhibitor of apoptosis (IAP) proteins are frequently upregulated in ovarian cancer, resulting the evasion and enhanced cellular survival. Birinapant, a synthetic second mitochondrial activator caspases (SMAC) mimetic, suppresses functions IAP order to enhance apoptotic pathways facilitate tumor death. Despite on-target activity, however, pre-clinical trials single-agent birinapant have exhibited minimal activity recurrent cancer setting. To augment therapeutic potential birinapant, we...
Abstract Sphere forming cells persist in the ascitic fluid of patients with high-grade serous ovarian cancer after first-line therapy and likely contribute to relapse metastasis. These residual tumor spheres, which are enriched for by up 95% based on detectable TP53 mutations, slow growing, resistant platinum-based chemotherapy, remain a large obstacle towards durable remission. Screening established, rapidly dividing monolayer cell lines proliferation assays has failed produce...