A5064117841- Cancer-related Molecular Pathways
- interferon and immune responses
- Cancer Research and Treatments
- NF-κB Signaling Pathways
- Skin and Cellular Biology Research
- RNA modifications and cancer
- Hair Growth and Disorders
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Hedgehog Signaling Pathway Studies
- Virus-based gene therapy research
- Cancer and Skin Lesions
- Molecular Biology Techniques and Applications
- Cell death mechanisms and regulation
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- melanin and skin pigmentation
- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- Nonmelanoma Skin Cancer Studies
- Advanced Breast Cancer Therapies
- dental development and anomalies
United States Food and Drug Administration
2006-2025
Center for Drug Evaluation and Research
2007-2023
Massachusetts General Hospital
2023
Harvard University
2023
National Institute on Deafness and Other Communication Disorders
2011
University at Buffalo, State University of New York
2011
National Institutes of Health
1990-2008
Food and Drug Administration
2008
Center for Biologics Evaluation and Research
2001-2003
Loyola University Medical Center
2002
The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage from exogenous chemical and physical mutagens. Therefore, we hypothesized that performs a similar putative endogenous mutagens, such as nitric oxide (NO). We report here exposure of human cells NO generated donor or overexpression inducible synthase (NOS2) results protein accumulation. In addition, expression wild-type (WT) variety cell lines, well murine fibroblasts, down-regulation NOS2...
On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla; Genentech, Inc.) for use as a single agent treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who previously received trastuzumab and taxane, separately or in combination. The clinical basis licensure was phase III trial 991 HER2-positive MBC that randomly allocated to receive (n=495) lapatinib combination capecitabine (n=496). coprimary endpoints were...
On June 8, 2012, the U.S. Food and Drug Administration (FDA) approved pertuzumab (Perjeta, Genentech) for use in combination with trastuzumab (Herceptin, docetaxel treatment of patients HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy disease. Approval was based on results a randomized, double-blind, placebo-controlled trial conducted 808 MBC. Patients were randomized (1:1) to receive (n = 402) placebo 406) docetaxel. The primary...
ABSTRACT mtCLIC/CLIC4 (referred to here as mtCLIC) is a p53- and tumor necrosis factor alpha-regulated cytoplasmic mitochondrial protein that belongs the CLIC family of intracellular chloride channels. mtCLIC associates with inner membrane. Dual regulation by two stress response pathways suggested this channel might contribute cellular cytotoxic stimuli. DNA damage or overexpression p53 upregulates induces apoptosis. Overexpression transient transfection reduces membrane potential, releases...
A novel chloride intracellular channel (CLIC) gene, clone mc3s5/mtCLIC, has been identified from differential display analysis of differentiating mouse keratinocytes p53+/+ and p53−/− mice. The 4.2-kilobase pair cDNA contains an open reading frame 762 base pairs encoding a 253-amino acid protein with two putative transmembrane domains. mc3s5/mtCLIC shares extensive homology family organelle channels but is the first shown to be differentially regulated. mRNA expressed greatest extent in vivo...
Tripartite motif protein 32, Trim32, mRNA and expression was elevated in independently transformed tumorigenic keratinocytes of a mouse epidermal carcinogenesis model, ultraviolet B (UVB)-induced squamous cell carcinomas (SCC), approximately 20-25% chemically induced papillomas human head neck SCCs. This suggests that Trim32 occurs frequently experimental is relevant to cancer. Transduced increased colony number an vitro transformation assay thickening vivo when skin-grafted athymic nu/nu...
Here we report on investigation of the role POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from cell cycle, migrate suprabasally, terminally differentiate to form a multilayered, stratified epithelium. The expression Skn-1a/i Tst-1 is linked keratinocyte differentiation vivo vitro, whereas ubiquitous factor Oct-1 expressed highly both post-mitotic keratinocytes. Analysis gene-deleted mice reveals...
Abstract Inflammation-induced activation of proto-oncogenic NF-κB/REL and dysfunction tumor suppressor TP53/p63/p73 family transcription factors are key events in cancer progression. How inflammatory signaling coordinates dysregulation these two factor families during oncogenesis remains incompletely understood. Here, we observed that oncoprotein c-REL TAp73 coexpressed complex with ΔNp63α the nucleus a subset head neck squamous cell carcinoma (HNSCC) lines mutant (mt)TP53. TNF-α,...
Abstract On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for treatment of adult patients HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one which was disease. Approval based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab trastuzumab, chemotherapy. The primary efficacy endpoint progression-free...
Abstract Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer worldwide, with incidence anticipated to increase by 30% 2030. HNSCC occurs often in men their 50-60s, although among women younger individuals rising. The current standard-of-care practices are surgical resection chemoradiotherapy. tumors exhibit frequent mutation of TP53 (72% tumors). Two additional members gene family, TP63 TP73, frequently altered HNSCC. encodes two major isoforms, ΔNp63 TAp63...
The p53 homologue DeltaNp63alpha is overexpressed and inhibits apoptosis in a subset of human squamous cell carcinomas (SCC). Here, we report that normal keratinocytes overexpressing carcinoma cells, physically associates with phosphorylated, transcriptionally active nuclear c-Rel, factor-kappaB family member, resulting increased c-Rel accumulation. This accumulation the associated enhanced proliferation driven by elevated are attenuated small interfering RNA or overexpression mutant...
Initiating as protruding ridges above and below the optic vesicle, eyelids of mice grow across eye temporarily fuse in fetal life. Mutations a number genes disrupt this developmental process result birth defect, "open-eyelids at birth." Here we show that critical event for eyelid induction occurs embryonic day 11.5 (E11.5) when single cell-layered ectoderm presumptive territory increases proliferation undergoes morphologic transition to form cube-shaped epithelial cells. Using embryos...