112 results found
Smith P, Crook T, 2007, Epigenetic inactivation implies independent functions for insulin-like growth factor binding protein (IGFBP)-related protein 1 and the related IGFBPL1 in inhibiting breast cancer phenotypes, Clin. Cancer Res.
Crook T, Smith P, Syed N, et al., 2007, Conserved epigenetic changes in sporadic and HIV-associated high-grade B-cell lymphomas, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Bergamaschi D, Lu X, 2006, iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53, Nature Genetics
Crighton D, Wilkinson S, O'Prey J, et al., 2006, DRAM, a p53-induced modulator of autophagy, is critical for apoptosis, Cell, Vol: 126
Inactivation of cell death is a major step in tumor development, and p53, a tumor suppressor frequently mutated in cancer, is a critical mediator of cell death. While a role for p53 in apoptosis is well established, direct links to other pathways controlling cell death are unknown. Here we describe DRAM (damage-regulated autophagy modulator), a p53 target gene encoding a lysosomal protein that induces macroautophagy, as an effector of p53-mediated death. We show that p53 induces autophagy in a DRAM-dependent manner and, while overexpression of DRAM alone causes minimal cell death, DRAM is essential for p53-mediated apoptosis. Moreover, analysis of DRAM in primary tumors revealed frequent decreased expression often accompanied by retention of wild-type p53. Collectively therefore, these studies not only report a stress-induced regulator of autophagy but also highlight the relationship of DRAM and autophagy to p53 function and damage-induced programmed cell death.
Stebbing J, Bower M, Syed N, et al., 2006, Epigenetics: an emerging technology in the diagnosis and treatment of cancer, PHARMACOGENOMICS, Vol: 7, Pages: 747-757, ISSN: 1462-2416
Stebbing J, Crook T, 2006, Epigenetics: an emerging technology in the diagnosis and treatment of cancer, Pharmacogenomics
Gasco M, Syed N, Smith P, et al., 2006, A multi-gene algorithm as predictor of response to chemo-radiotherapy in head and neck cancer., J Clin Oncol, Vol: 24
10086 Background: Chemo-radiotherapy results in clinical cure for stage III/IV head and neck cancer in approximately 40% of cases, with significant treatment-associated morbidity and mortality. Molecular genetic factors predictive of treatment outcome would clearly be of value in selection of patients with highest probability of response. We have analysed the structure and epigenetic regulation of specific genes as possible predictors of outcome to chemo-radiotherapy. The genes analyzed were: p53 (single nucleotide polymorphism (SNP) and mutation), MDM2 (SNP), Chfr (methylation), CRABP1 (methylation). METHODS: 84 patients with locally advanced head and neck cancer receiving cisplatin-based chemo-radiotherapy were studied. SNP genotypes were determined by direct sequencing of DNA from normal tissue. Acquired mutations in p53 and aberrant methylation in the CpG islands of specific genes were analyzed by direct sequencing and methylation-specific PCR. RESULTS: There were 6 treatment-related deaths in 84 patients, all occurring in cases with germ-line haplotype p53 72 Arg/Arg, MDM2 309T/T. At the time of analysis, 39/84 (46%) patients had progressed or died, with median time to progression or death = 17.3 months. Complete response was more common in patients whose genetic/epigenetic profile was p53 72 Arg/Arg wild type, MDM2 309 G/G, Chfr methylated, CRABP1 methylated, compared to the profile p53 72 Arg/Arg mutant, MDM2 309 T/T, Chfr unmethylated, CRABP1 unmethylated (91% vs 46%, log rank p = 0.002). Progression-free survival was significantly longer for patients with the profile p53 72 Arg/Arg wild type, MDM2 309 G/G, Chfr methylated, CRABP1 methylated, compared to those with p53 72 Arg/Arg mutant, MDM2 309 T/T, Chfr unmethylated, CRABP1 unmethylated (% surviving progression-free at 2 years = 74% vs 36%, p = 0.001). Overall survival was significantly longer in patients with the profile p53 72 Arg/Arg wild type, MDM2 309 G/G, Chfr methylated, CRABP1 methylated compared
Smith P, Syed N, Crook T, 2006, Epigenetic inactivation implies a tumor suppressor function in hematologic malignancies for Polo-like kinase 2 but not Polo-like kinase 3, Cell Cycle
Syed N, Crook T, 2006, Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies, Blood
Syed N, Smith P, Sullivan A, et al., 2006, Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies, BLOOD, Vol: 107, Pages: 250-256, ISSN: 0006-4971
Sullivan A, Crook T, 2004, Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo, Oncogene
Gasco M, Smith P, Sullivan A, et al., 2004, TRANSCRIPTIONAL SILENCING OF THE G2 CHECKPOINT CHFR INFLUENCES CLINICAL OUTCOME IN HEAD AND NECK CANCER, ANNALS OF ONCOLOGY, Vol: 15, Pages: 49-49, ISSN: 0923-7534
Sullivan A, Syed N, Gasco M, et al., 2004, Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo., Oncogene, Vol: 23, Pages: 3328-3337
Bergamaschi D, Gasco M, Hiller L, et al., 2003, p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis, CANCER CELL, Vol: 3, Pages: 387-402, ISSN: 1535-6108
Bergamaschi D, Crook T, 2003, p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis, Cancer Cell
Bugeon L, Danou A, Carpentier D, et al., 2003, Inducible gene silencing in podocytes: A new tool for studying glomerular function, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 14, Pages: 786-791, ISSN: 1046-6673
bugeon L, danou A, carpenter D, et al., 2003, Inducible gene silencing in podocytes: a new tool for studying glomerular function, Journal of the American Society of Nephrology14, Vol: 14
Glomerular filtration is one of the primary functions of the kidney. Podocytes, a highly specialized cell type found in glomeruli, are believed to play a critical role in that function. Null mutations of genes expressed in podocytes like WT1, nephrin, and NEPH1 result in an embryo and perinatal lethal phenotype and therefore do not allow the functional analysis of these genes in the adult kidney. Here is describes the generation of a model that will allow such studies. We have engineered transgenic mice in which the disruption of targeted genes can be induced in a temporally controlled fashion in podocytes. For this, a transgene encoding the mutated estrogen receptor-Cre recombinase fusion protein was introduced into the mouse genome. Animals were crossed with Z/AP reporter mice to test for efficient and inducible recombination. We found that, after injection of inducer drug tamoxifen, Cre fusion protein translocates to the nuclei of podocytes, where it becomes active and mediates recombination of DNA carrying loxP target sequences. These animals provide for the first time a tool for silencing genes selectively in podocytes of adult animals.
Kropf P, Herath S, Tewari R, et al., 2002, Identification of two distinct subpopulations of Leishmania major-specific T helper 2 cells, INFECTION AND IMMUNITY, Vol: 70, Pages: 5512-5520, ISSN: 0019-9567
kropf P, herath S, tewari R, et al., 2002, Identification of two distinct subpopulations of Leishmania major-specific T helper 2 cells, Infection and Immunity, Vol: 70
It is widely accepted that a strong Th2 response is responsible for nonhealing Leishmania major infections in BALB/c mice. This Th2 response has been thoroughly documented by measuring the levels of Th2 cytokines produced by CD4(+) T cells present in the lymphoid organs by enzyme-linked immunosorbent assay and PCR. However, the cytokine profile of L. major-specific Th2 cells has never been determined. In this study, we used the recently described Th2 marker T1/ST2 to characterize Th2 cells during the course of nonhealing L. major infection. We analyzed the intracellular cytokine profile of CD4(+) T1/ST2(+) T cells and showed that they clearly displayed a Th2 phenotype, as they expressed interleukin 4 (IL-4), IL-10, and IL-5. In addition, we detected another population of Th2 cells among the CD4(+) T1/ST2(-) T cells that expressed IL-4 and IL-10 but excluded IL-5. In summary, we show here that two type 2 subpopulations are present in the lymphoid organs of L. major-infected BALB/c mice; Th2 cells from both subsets expressed IL-4 and IL-10, but they could be distinguished by their expression of IL-5 and T1/ST2.
Bugeon L, Syed N, Dallman MJ, 2000, A fast and efficient method for transiently transfecting ES cells: application to the development of systems for conditional gene expression, TRANSGENIC RESEARCH, Vol: 9, Pages: 229-232, ISSN: 0962-8819
Bugeon L, Syed N, Dallman M, 2000, A fast and efficient method for transiently transfecting ES cells: application to the development of systems for conditional gene expression, Transgenic Research, Vol: 9
Classically, mouse embryonic stem (ES) cells are transfected by electroporation, a method that requires a large number of cells. Here we describe a protocol using a liposome based transfection agent that is a very simple, rapid and cost effective way of transiently transfecting very low numbers of ES cells. We found this method very useful in screening a large number of ES clones when working with inducible expression systems in which at least two elements are required for regulated expression of the gene of interest. After stable transfection of the first component, clones can be easily and rapidly screened for expression of the gene of interest by transiently transfecting the second component of the system using this protocol.
Lam KM, Syed N, Crawford DH, 1991, Circulating Epstein-Barr virus-carrying B cells in acute malaria, Lancet
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