Publications by authors named "Victoria Salter"

9 Publications

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Colonic Goblet Cell Carcinoid: Rarity of a Rarity! A Case Report and Review of Literature.

Chirurgia (Bucur) 2020 Jan-Feb;115(1):102-111

Goblet cell carcinoids (GCC) are extremelyrare neuroendocrine tumours, and characterised by their unique combination of two types of cancer cells âÃÂ" neuroendocrine (carcinoid) and epithelial (adeno-carcinoma). In spite of the fact that GCC is regarded as Neuro-Endocrine Tumour (NET), it does not illicit carcinoid syndrome. GCC usually arises in the appendix and accounting for less than 14% of all appendiceal tumours.Primary extra-appendiceal GCC have been reported as stomach, duodenum, small intestine, colon and rectum. The paper presents a rare case of GCC of the ascending colon in a 57-year-old male.
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http://dx.doi.org/10.21614/chirurgia.115.1.102DOI Listing
March 2020

ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1.

Nat Cell Biol 2014 Nov 26;16(11):1092-104. Epub 2014 Oct 26.

Ludwig Institute for Cancer Research Ltd, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Epithelial to mesenchymal transition (EMT), and the reverse mesenchymal to epithelial transition (MET), are known examples of epithelial plasticity that are important in kidney development and cancer metastasis. Here we identify ASPP2, a haploinsufficient tumour suppressor, p53 activator and PAR3 binding partner, as a molecular switch of MET and EMT. ASPP2 contributes to MET in mouse kidney in vivo. Mechanistically, ASPP2 induces MET through its PAR3-binding amino-terminus, independently of p53 binding. ASPP2 prevents β-catenin from transactivating ZEB1, directly by forming an ASPP2-β-catenin-E-cadherin ternary complex and indirectly by inhibiting β-catenin's N-terminal phosphorylation to stabilize the β-catenin-E-cadherin complex. ASPP2 limits the pro-invasive property of oncogenic RAS and inhibits tumour metastasis in vivo. Reduced ASPP2 expression results in EMT, and is associated with poor survival in hepatocellular carcinoma and breast cancer patients. Hence, ASPP2 is a key regulator of epithelial plasticity that connects cell polarity to the suppression of WNT signalling, EMT and tumour metastasis.
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http://dx.doi.org/10.1038/ncb3050DOI Listing
November 2014

ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63.

Proc Natl Acad Sci U S A 2013 Oct 14;110(44):17969-74. Epub 2013 Oct 14.

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, and Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.

Squamous cell carcinoma (SCC) is highly malignant and refractory to therapy. The majority of existing mouse SCC models involve multiple gene mutations. Very few mouse models of spontaneous SCC have been generated by a single gene deletion. Here we report a haploinsufficient SCC mouse model in which exon 3 of the Tp53BP2 gene (a p53 binding protein) was deleted in one allele in a BALB/c genetic background. Tp53BP2 encodes ASPP2 (ankyrin repeats, SH3 domain and protein rich region containing protein 2). Keratinocyte differentiation induces ASPP2 and its expression is inversely correlated with p63 protein in vitro and in vivo. Up-regulation of p63 expression is required for ASPP2(Δexon3/+) BALB/c mice to develop SCC, as heterozygosity of p63 but not p53 prevents them from developing it. Mechanistically, ASPP2 inhibits ΔNp63 expression through its ability to bind IκB and enhance nuclear Rel/A p65, a component of the NF-κB transcription complex, which mediates the repression of p63. Reduced ASPP2 expression associates with tumor metastasis and increased p63 expression in human head and neck SCCs. This study identifies ASPP2 as a tumor suppressor that suppresses SCC via inflammatory signaling through NF-κB-mediated repression of p63.
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http://dx.doi.org/10.1073/pnas.1309362110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816480PMC
October 2013

Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP.

Cancer Cell 2013 May 25;23(5):618-33. Epub 2013 Apr 25.

Ludwig Institute for Cancer Research, University of Oxford, Oxford OX3 7DQ, UK.

Nearly 90% of human melanomas contain inactivated wild-type p53, the underlying mechanisms for which are not fully understood. Here, we identify that cyclin B1/CDK1-phosphorylates iASPP, which leads to the inhibition of iASPP dimerization, promotion of iASPP monomer nuclear entry, and exposure of its p53 binding sites, leading to increased p53 inhibition. Nuclear iASPP is enriched in melanoma metastasis and associates with poor patient survival. Most wild-type p53-expressing melanoma cell lines coexpress high levels of phosphorylated nuclear iASPP, MDM2, and cyclin B1. Inhibition of MDM2 and iASPP phosphorylation with small molecules induced p53-dependent apoptosis and growth suppression. Concurrent p53 reactivation and BRAFV600E inhibition achieved additive suppression in vivo, presenting an alternative for melanoma therapy.
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http://dx.doi.org/10.1016/j.ccr.2013.03.013DOI Listing
May 2013

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification.

Proc Natl Acad Sci U S A 2011 Oct 19;108(40):16645-50. Epub 2011 Sep 19.

Nuffield Department of Clinical Medicine, Ludwig Institute for Cancer Research, University of Oxford, Oxford OX3 7DQ, United Kingdom.

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is the most ancient member of the ASPP family of proteins and an evolutionarily conserved inhibitor of p53. iASPP is also a binding partner and negative regulator of p65RelA. Because p65RelA and the p53 family members often have opposite effects in controlling cell fate, it is important to understand the cellular context in which iASPP can regulate their activities. To address this question and to study the biological importance of iASPP in vivo, we generated a transgenic mouse in which iASPP expression is controlled by the Cre/loxP recombination system. We observed that iASPP is able to prevent premature cellular senescence in mouse embryonic fibroblasts. iASPP loss resulted in increased differentiation of primary keratinocytes both in vitro and in vivo. In stratified epithelia, nuclear iASPP often colocalized with p63 in the nuclei of basal keratinocytes. Consistent with this, iASPP bound p63 and inhibited the transcriptional activity of both TAp63α and ΔNp63α in vitro and influenced the expression level of p63-regulated genes such as loricrin and involucrin in vivo. In contrast, under the same conditions, p65RelA was frequently expressed as a cytoplasmic protein in the suprabasal layers of stratified epithelia and rarely colocalized with nuclear iASPP. Thus, iASPP is likely to control epithelial stratification by regulating p63's transcriptional activity, rather than p65RelA's. This study identifies iASPP as an inhibitor of senescence and a key player in controlling epithelial stratification.
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http://dx.doi.org/10.1073/pnas.1102292108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189025PMC
October 2011

Neuro-ophthalmic complications in giant cell arteritis.

Curr Allergy Asthma Rep 2008 Jul;8(4):323-30

Department of Rheumatology, Southend University Hospital, Prittlewell Chase, Westcliffe-on-Sea, Essex, SS0 0RY, UK.

Giant cell arteritis (GCA) is a medical emergency characterized by systemic inflammation and critical ischemia. Neuro-ophthalmic complications occur early, with permanent vision loss in up to one fifth of patients. This mainly results from failure of prompt recognition and treatment. Diagnosis of GCA is often preceded by unrecognized symptoms, including constitutional upset and jaw claudication. Features predictive of permanent visual loss include jaw claudication and temporal artery abnormalities on physical examination. These patients often do not mount high inflammatory responses. Modern imaging techniques show diagnostic promise, and have led to an increased recognition of major artery involvement in GCA. However, temporal artery biopsy remains the gold standard for investigation. Intimal hyperplasia on histologic examination is associated with neuro-ophthalmic complications. The mainstay of therapy remains corticosteroids. Experience using conventional disease-modifying drugs has been mixed, and biologic therapies require further evaluation for their steroid-sparing potential.
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http://dx.doi.org/10.1007/s11882-008-0052-4DOI Listing
July 2008

Medical conditions in works of art.

Br J Hosp Med (Lond) 2008 Feb;69(2):91-4

North Central Thames Foundation School, UK.

With their stark contrast and blurred boundaries, the relationship between science, medicine and art has long been a fascinating area of exploration. The depiction of medical conditions in art has enhanced our understanding of the evolution of disease and its treatment, but exact diagnosis of the underlying medical conditions can be difficult. This article reviews some paintings suggesting underlying medical diagnoses under specialty-based headings.
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http://dx.doi.org/10.12968/hmed.2008.69.2.28354DOI Listing
February 2008