A5061796830- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Inflammatory mediators and NSAID effects
- Genetic and rare skin diseases.
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Cancer and Skin Lesions
- Skin Protection and Aging
- Cancer Research and Treatments
- melanin and skin pigmentation
- Autophagy in Disease and Therapy
- Sirtuins and Resveratrol in Medicine
- Estrogen and related hormone effects
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell death mechanisms and regulation
- Microtubule and mitosis dynamics
- Redox biology and oxidative stress
- Antioxidant Activity and Oxidative Stress
Columbia University Irving Medical Center
2009-2024
Columbia University
2009-2021
Cancer Research Center
2009-2014
New York Proton Center
2011
National Cancer Institute
2005-2010
University of California, San Francisco
2010
Stanford University
2010
University of Alabama at Birmingham
2010
Abstract The TINCR ( T erminal differentiation- I nduced N on- C oding R NA) gene is selectively expressed in epithelium tissues and involved the control of human epidermal differentiation wound healing. Despite its initial report as a long non-coding RNA, locus codes for highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we identification tumor suppressor squamous cell carcinoma (SCC). upregulated by UV-induced DNA damage TP53-dependent manner...
Abnormal activation of the hedgehog-signaling pathway is pivotal abnormality driving growth basal cell carcinomas (BCCs), most common type human cancer. Antagonists this such as cyclopamine may therefore be useful for treatment and other hedgehog-driven tumors. We report here that chronic oral administration dramatically reduces ( approximately 66%) UVB induced carcinoma formation in Ptch1(+/-) mice. Fas expression low murine but up-regulated presence smoothened (SMO) antagonist,...
Mutations in the tumor suppressor p53 are detectable over 50% of all human malignancies. Mutant protein is incapable transactivating its downstream target genes that required for DNA repair and apoptosis. Chronic exposure to UVB induces mutations carcinogenic both murine skin. CP-31398, a styrylquinazoline compound, restores functions mutant forms cells. However, effectiveness vivo remains unclear. Here, we demonstrate CP-31398 blocked UVB-induced skin carcinogenesis was associated with...
Abstract Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalence, is closely associated barrier defects. A cytokine related to severity and inhibition of keratinocyte differentiation IL-31. To identify its molecular targets, IL-31–dependent gene expression was determined in three-dimensional organotypic models. IL-31–regulated genes are involved the formation an intact physical barrier. Many these were poorly induced during as consequence IL-31 treatment, resulting...
Abstract: Resveratrol ( trans ‐3,4′,5‐trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found in grapes, and has been shown to inhibit the growth of various types cancer cells. We investigated mechanism antiproliferative effect resveratrol A431‐transformed keratinocytes harbouring mutant p53, show that it accompanied by G1 cell cycle arrest, which coincides with marked inhibition regulatory proteins, including cyclins A D1 cyclin‐dependent kinase (CDK)6 p53‐independent...
Abstract In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study their more common basal cell carcinoma (BCC) carcinogenesis. We first compared relative anti-BCC effects genetic deletion NSAID pharmacologic inhibition cyclooxygenase (COX) enzymes Ptch1+/− mice. then assessed celecoxib on development BCCs a 3-year, double-blinded, randomized clinical trial...
DNA-damaging agents can induce premature senescence in cancer cells, which contributes to the static effects of cancer. However, senescent cells may re-enter cell cycle and lead tumor relapse. Understanding mechanisms that control viability be helpful eliminating these before they regrow. Treating human squamous carcinoma (SCC) with anti-cancer compounds, resveratrol doxorubicin, triggered p53-independent by invoking oxidative stress-mediated DNA damage. This process involved mTOR-dependent...
DNA damage is a well-known initiator of tumorigenesis. Studies have shown that most cancer cells rely on aerobic glycolysis for their bioenergetics. We sought to identify molecular link between genomic mutations and metabolic alterations in neoplastic transformation. took advantage the intrinsic instability arising xeroderma pigmentosum C (XPC). The XPC protein plays key role recognizing nucleotide excision repair, patients with deficiency increased incidence skin other malignancies. In...
The regulation of DNA repair enzymes is crucial for cancer prevention, initiation, and therapy. We have studied the effect ultraviolet B (UVB) radiation on expression two nucleotide excision factors (XPC XPD) in human keratinocytes. show that hypoxia-inducible factor-1α (HIF-1α) involved XPC XPD. Early UVB-induced downregulation HIF-1α increased mRNA due to competition between Sp1 their overlapping binding sites. Late enhanced phosphorylation protein upregulated by direct a separate hypoxia...
p38 mitogen-activated protein kinases (MAPKs) respond to a wide range of extracellular stimuli. While the inhibition signaling is implicated in impaired capacity repair ultraviolet (UV)-induced DNA damage—a primary risk factor for human skin cancers—its mechanism action carcinogenesis remains unclear, as both anti-proliferative and survival functions have been previously described. In this study, we utilized cultured keratinocytes, murine tumorigenesis models, cutaneous squamous cell...
Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention basal cell carcinomas (BCCs), majority have mutations tumor-suppressor gene known as patched (PTCH). To assess this possibility, we overexpressed skin Ptch1+/– mice using...
Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention basal cell carcinomas (BCCs), majority have mutations tumor-suppressor gene known as patched (PTCH). To assess this possibility, we overexpressed skin Ptch1+/– mice using...
The mammalian epidermis is maintained by proliferation and differentiation of epidermal progenitor cells in a stereotyped developmental program. Here we report that tissue-specific deletion the UV-damaged DNA-binding protein 1 (DDB1) mouse led to dramatic accumulation c-Jun p21Cip1, arrest cell cycle at G(2)/M, selective apoptosis proliferating cells, as result, nearly complete loss hair follicles. Deletion p53 tumor suppressor gene partially rescued epithelial from death allowed for...
Macroautophagy is a cellular response to various environmental stresses that ensures lysosomal degradation of long-lived and damaged proteins organelles. It occurs through the formation an autophagosome, which then fuses with lysosome form autolysosome. Depending on context, autophagy may promote cancer cell survival or it serve as mechanism tumor suppression. Herein, we show resveratrol, natural phytoalexin, induces premature senescence in human A431 SCC cells, resveratrol-induced...
// Sandeep C. Chaudhary 1, * , Xiuwei Tang 3, Aadithya Arumugam 1 Changzhao Li Ritesh K. Srivastava Zhiping Weng Jianmin Xu Xiao Zhang 2, 6 Arianna L. Kim 3 Kristopher McKay 4 Craig A. Elmets Levy Kopelovich 5 David R. Bickers Mohammad Athar Department of Dermatology, University Alabama at Birmingham, AL 35294–0019, USA 2 Biostatistics, College Physicians & Surgeons, Columbia University, New York, NY 10032, Division Dermatopathology, 35294–4550, Medicine, Weill Cornell Medical College,...