ORCID Profile
0000-0002-4418-947X
Current Organisations
Universitat de Girona
,
The University of Auckland
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Publisher: Wiley
Date: 11-05-2005
DOI: 10.1002/AJMG.A.30763
Abstract: Robertsonian translocations (RTs) are amongst the most common chromosome abnormalities, but being essentially balanced are not usually associated with phenotypic abnormality. Despite being dicentric, RTs are almost always transmitted stably through cell ision without chromosome breakage. We have investigated spontaneous fission of der(13 )(q10 q10) chromosomes in eight in iduals from two unrelated kindreds with a view to assessing clinical significance and to seek an explanation for the peculiar heritable instability displayed by these chromosomes. In Family 1, fission products were observed in five members in three generations. The instability was observed in cells derived from chorionic villus and lymphocytes. In Family 2, the same phenomenon was observed in amniocytes from two separate pregnancies and maternal blood lymphocytes. Detailed FISH analysis of these RTs showed them to be dicentric with an unremarkable pericentromeric structure. Notably, combined immunofluoresence and FISH analysis showed the presence of the centromere-specific proteins CENP-A and CENP-E, consistent with functional dicentricity in >75% of cells analyzed. The fission products are, therefore, presumed to be the result of sporadic, bipolar kinetochore attachment, anaphase bridging with resultant inter-centromeric breakage in a small proportion of mitoses. None of the eight carriers shows phenotypic abnormality and therefore, for prenatal counseling purposes, there appears to be no increased specific risk associated with this phenomenon.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1093/AJCN/NQZ279
Abstract: Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. Women (n = 40 age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON containing A1 and A2 β-casein and lactose), a2 Milk (A2M exclusively containing A2 β-casein with lactose), or lactose-free conventional milk (LF-CON containing A1 and A2 β-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P < 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min P < 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. In LI in iduals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.TEM.2007.10.003
Abstract: Trefoil factors (TFFs), in particular TFF1, are classical estrogen-regulated genes and have served as markers of estrogen gene regulation by various environmental estrogens. TFFs are also regulated by several other factors including growth hormone (hGH), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF) and various oncogenic stimuli. TFFs are secreted proteins present in serum and possess the potential to act as growth factors promoting cell survival, anchorage-independent growth and motility. Recent compelling evidence has emerged from experimental and clinical studies to indicate a pivotal role of TFFs in oncogenic transformation, growth and metastatic extension of common human solid tumours. This review will summarize the current evidence for the involvement of TFFs in human cancer.
Publisher: The Endocrine Society
Date: 05-2008
DOI: 10.1210/EN.2008-0286
Abstract: Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage-independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma.
Publisher: Proceedings of the National Academy of Sciences
Date: 14-04-2004
Abstract: Centromere repositioning provides a potentially powerful evolutionary force for reproductive isolation and speciation, but the underlying mechanisms remain ill-defined. An attractive model is through the simultaneous inactivation of a normal centromere and the formation of a new centromere at a hitherto noncentromeric chromosomal location with minimal detrimental effect. We report a two-generation family in which the centromeric activity of one chromosome 4 has been relocated to a euchromatic site at 4q21.3 through the epigenetic formation of a neocentromere in otherwise cytogenetically normal and mitotically stable karyotypes. Strong epigenetic inactivation of the original centromere is suggested by retention of 1.3 megabases of centromeric α-satellite DNA, absence of detectable molecular alteration in chromosome 4-centromereproximal p- and q-arm sequences, and failure of the inactive centromere to be reactivated through extensive culturing or treatment with histone deacetylase inhibitor trichostatin A. The neocentromere binds functionally essential centromere proteins (CENP-A, CENP-C, CENP-E, CENP-I, BUB1, and HP1), although a moderate reduction in CENP-A binding and sister-chromatid cohesion compared with the typical centromeres suggests possible underlying structural/functional differences. The stable mitotic and meiotic transmissibility of this pseudodicentric-neocentric chromosome in healthy in iduals and the ability of the neocentric activity to form in a euchromatic site in preference to a preexisting alphoid domain provide direct evidence for an inherent mechanism of human centromere repositioning and karyotype evolution “in progress.” We discuss the wider implication of such a mechanism for meiotic drive and the evolution of primate and other species.
Publisher: Portland Press Ltd.
Date: 23-12-2009
DOI: 10.1042/CS20090503
Abstract: Malignant and trophoblastic cells share the capacity to migrate and invade surrounding tissues however, trophoblast invasion during implantation is tightly regulated, whereas that associated with tumour progression is not. It is likely that similar mechanisms underlie the dynamic regulation of cell invasion and migration in both cases, and that these are based on epigenetic processes. This hypothesis is supported by recent results demonstrating that expression of the intercellular adhesion molecule E-cadherin, deregulation of which is associated with increased cell motility and invasive potential in cancer, is under epigenetic control in trophoblast cell lines. Further elucidation of the epigenetic pathways shared by trophoblasts and malignant cells is likely to lead to the identification of common diagnostic approaches for the early identification both of cancer and pathological pregnancies involving aberrant trophoblast invasion.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2021
DOI: 10.1038/S42003-021-02594-0
Abstract: Type 1 diabetes (T1D) etiology is complex. We developed a machine learning approach that ranked the tissue-specific transcription regulatory effects for T1D SNPs and estimated their relative contributions to conversion to T1D by integrating case and control genotypes (Wellcome Trust Case Control Consortium and UK Biobank) with tissue-specific expression quantitative trait loci (eQTL) data. Here we show an eQTL (rs6679677) associated with changes to AP4B1-AS1 transcript levels in lung tissue makes the largest gene regulatory contribution to the risk of T1D development. Luciferase reporter assays confirmed allele-specific enhancer activity for the rs6679677 tagged locus in lung epithelial cells ( i.e . A549 cells C A reduces expression, p = 0.005). Our results identify tissue-specific eQTLs for SNPs associated with T1D. The strongest tissue-specific eQTL effects were in the lung and may help explain associations between respiratory infections and risk of islet autoantibody seroconversion in young children.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1593/NEO.10916
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1002/MDS.28144
Publisher: Elsevier BV
Date: 12-1999
Publisher: The Endocrine Society
Date: 29-01-2010
DOI: 10.1210/EN.2009-0979
Abstract: Here, we provide evidence for a functional role of artemin (ARTN) in progression of endometrial carcinoma (EC). Increased ARTN protein expression was observed in EC compared with normal endometrial tissue, and ARTN protein expression in EC was significantly associated with higher tumor grade and invasiveness. Forced expression of ARTN in EC cells significantly increased total cell number as a result of enhanced cell cycle progression and cell survival. In addition, forced expression of ARTN significantly enhanced anchorage-independent growth and invasiveness of EC cells. Moreover, forced expression of ARTN increased tumor size in xenograft models and produced highly proliferative, poorly differentiated, and invasive tumors. The ARTN-stimulated increases in oncogenicity and invasion were mediated by increased expression and activity of AKT1. Small interfering RNA-mediated depletion or antibody inhibition of ARTN significantly reduced oncogenicity and invasion of EC cells. Thus, inhibition of ARTN may be considered as a potential therapeutic strategy to retard progression of EC.
Publisher: American Geophysical Union (AGU)
Date: 12-2008
DOI: 10.1029/2008GC002204
Publisher: Springer Science and Business Media LLC
Date: 13-04-2009
DOI: 10.1038/ONC.2009.66
Abstract: We report that artemin, a member of the glial cell line-derived neurotrophic factor family of ligands, is oncogenic for human mammary carcinoma. Artemin is expressed in numerous human mammary carcinoma cell lines. Forced expression of artemin in mammary carcinoma cells results in increased anchorage-independent growth, increased colony formation in soft agar and in three-dimensional Matrigel, and also promotes a scattered cell phenotype with enhanced migration and invasion. Moreover, forced expression of artemin increases tumor size in xenograft models and leads to highly proliferative, poorly differentiated and invasive tumors. Expression data in Oncomine indicate that high artemin expression is significantly associated with residual disease after chemotherapy, metastasis, relapse and death. Artemin protein is detectable in 65% of mammary carcinoma and its expression correlates to decreased overall survival in the cohort of patients. Depletion of endogenous artemin with small interfering RNA, or antibody inhibition of artemin, decreases the oncogenicity and invasiveness of mammary carcinoma cells. Artemin is therefore oncogenic for human mammary carcinoma, and targeted therapeutic approaches to inhibit artemin function in mammary carcinoma warrant consideration.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2010
DOI: 10.1038/ONC.2010.71
Abstract: We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Meta-analysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN-stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by small-interfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen-resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma.
Publisher: American Geophysical Union (AGU)
Date: 11-2014
DOI: 10.1002/2014GC005477
Publisher: Proceedings of the National Academy of Sciences
Date: 05-11-2013
Abstract: The gene responsible for the X-linked form of Opitz syndrome (OS), Midline-1 ( MID1 ), encodes an E3 ubiquitin ligase and was reported to guide the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). But whether and how it is involved in neural development is unclear. We demonstrate here that Mid1-dependent PP2Ac turnover is involved in axon development. Knocking down or knocking out Mid1 not only promotes axon growth and branching in vitro, but also accelerates axon elongation and disrupts the pattern of callosal projection in mouse cortex. These defects can be reversed by down-regulating the accumulated PP2Ac in Mid1-depleted cells. Dysfunction of this Mid1–PP2Ac pathway may underlie neural symptoms of OS patients.
Publisher: Springer Science and Business Media LLC
Date: 12-2004
DOI: 10.1007/S10577-005-5377-4
Abstract: We have expressed an EGFP-CENP-A fusion protein in human cells in order to quantitate the level of CENP-A incorporated into normal and variant human centromeres. The results revealed a 3.2-fold difference in the level of CENP-A incorporation into alpha-satellite repeat DNA-based centromeres, with the Y centromere showing the lowest level of all normal human chromosomes. Identification of in idual chromosomes revealed a statistically significant, though not absolute, correlation between chromosome size and CENP-A incorporation. Analysis of three independent neocentromeres revealed a significantly reduced level of CENP-A compared to normal centromeres. Truncation of a neocentric marker chromosome to produce a minichromosome further reduced CENP-A levels, indicating a remodelling of centromeric chromatin. These results suggest a role for increased CENP-A incorporation in the faithful segregation of larger chromosomes and support a model of centromere evolution in which neocentromeres represent ancestral centromeres that, through adaptive evolution, acquire satellite repeats to facilitate the incorporation of higher numbers of CENP-A containing nucleosomes, thereby facilitating the assembly of larger kinetochore structures.
Publisher: American Association for Cancer Research (AACR)
Date: 06-2010
DOI: 10.1158/1535-7163.MCT-09-1077
Abstract: We herein show that Artemin (ARTN), one of the glial cell line–derived neurotrophic factor family of ligands, promotes progression of human non–small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplastic compared with normal lung tissues increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were highly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA–mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC. Mol Cancer Ther 9(6) 1697–708. ©2010 AACR.
No related grants have been discovered for Jo Perry.