A5059252165- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Genetic factors in colorectal cancer
- Veterinary Practice and Education Studies
- Epigenetics and DNA Methylation
- Digestive system and related health
- Kruppel-like factors research
- Veterinary Equine Medical Research
- Cancer Cells and Metastasis
- Vector-Borne Animal Diseases
- Pancreatic and Hepatic Oncology Research
- Animal Disease Management and Epidemiology
- Cancer Genomics and Diagnostics
- Metabolism, Diabetes, and Cancer
- Peroxisome Proliferator-Activated Receptors
- Advanced Breast Cancer Therapies
- RNA modifications and cancer
- Liver physiology and pathology
- Colorectal Cancer Screening and Detection
- Human-Animal Interaction Studies
- Mathematical Biology Tumor Growth
- Agriculture and Farm Safety
- Brucella: diagnosis, epidemiology, treatment
Cardiff University
2011-2024
University of Louisiana at Lafayette
2024
Stem Cell Institute
2019
Dogs Trust
2018
Bowel Cancer UK
2015-2016
East Sussex County Council
2014
Transitional Learning Center
2010
Dana-Farber Cancer Institute
2010
Institute of Cancer Research
2010
Leiden University Medical Center
2010
Although Apc is well characterized as a tumor-suppressor gene in the intestine, precise mechanism of this suppression remains to be defined. Using novel inducible Ahcre transgenic line conjunction with loxP-flanked allele we, show that loss acutely activates Wnt signaling through nuclear accumulation β-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such Apc-deficient cells maintain “crypt progenitor-like” phenotype. Critically, for first time...
Inactivation of the Apc gene is recognized as key early event in development sporadic colorectal cancer (CRC), where its loss leads to constitutive activation β-catenin/T-cell factor 4 signaling and hence transcription Wnt target genes such c-Myc. Our other previous studies have shown that although cyclin D1 required for adenoma formation, it not immediately upregulated following within intestine, suggesting proliferation acute may be dependent on another D-type cyclin. In this study, we...
Abstract Wnt pathway deregulation is a common characteristic of many cancers. Only colorectal cancer predominantly harbours mutations in APC , whereas other types (hepatocellular carcinoma, solid pseudopapillary tumours the pancreas) have activating β‐catenin ( CTNNB 1) . We compared dynamics and potency vivo Within murine small intestine SI ), an mutation took much longer to achieve acquire crypt‐progenitor cell CPC ) phenotype than Apc or Gsk3 loss. colon, single was unable drive induce...
Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream the activation key. Here, using cre-lox technology, we deleted Apc gene adult mouse liver and observed a rapid increase nuclear beta-catenin c-Myc, which associated with an induction proliferation that led to hepatomegaly within 4 days deletion. To investigate responsible for these phenotypes, analyzed impact inactivating APC context deficiency potentially key effectors...
<h3>Background</h3> Rectal epithelial cell mitosis and crypt size, as well expression of proinflammatory genes including <i>macrophage migration inhibitory factor</i> (<i>MIF</i>), are increased 6 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients. Tests were carried out to determine whether these putative colorectal cancer risk biomarkers remained elevated long term RYGB, the mechanistic basis, functional consequences, <i>Mif</i> upregulation intestinal cells was...
We have previously shown that deficiency of the methyl binding domain protein Mbd2 dramatically reduces adenoma burden on an Apc(Min/+) background. To investigate mechanism underlying this phenomenon, we determined effect upon phenotypes imposed by conditional deletion Apc in small intestine. Microarray analysis demonstrated a partial suppression Wnt pathway absence Mbd2. also influenced one immediate cellular consequence loss, with normalization Paneth cell positioning. From mechanistic...
Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation this key pathway adult ovary is associated with subfertility and tumourigenesis. The roles Adenomatous polyposis coli 2 (APC2), little-studied regulator, homeostasis, fertility tumourigenesis have not previously been explored. Here, we demonstrate essential APC2 regulating homeostasis. A detailed analysis histology, gene expression, ovulation hormone levels was carried out 10 week old aged...
Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking treatment. We examined the effect of fluoxetine on in context a program included group cognitive‐behavioral therapy (six weeks) transdermal patch (ten weeks). In double‐blind randomized trial for...
Working horses, donkeys and mules suffer from numerous diseases clinical problems. However, there is little information on what owners perceive as important health concerns in their working animals.To identify prioritise with the other equids central Ethiopia using participatory methodologies.Participatory situation analysis (PSA).The study was conducted carthorse- donkey-owners 16 sites Ethiopia. Multiple methodologies were utilised, including ranking, matrices focus group discussions....
Abstract Aberrant Wnt signaling within breast cancer is associated with poor prognosis, but regulation of this pathway in tissue remains poorly understood and the consequences immediate or long-term dysregulation remain elusive. The exact contribution Wnt-regulating proteins adenomatous polyposis coli (APC) APC2 pathogenesis human are ill-defined, our analysis publically available array data sets indicates that tumors concomitant low expression both occurs more frequently ‘triple negative’...
Abstract While the Wnt/β-catenin pathway plays a critical role in maintenance of zonation ammonia metabolizing enzymes adult liver, mechanisms responsible for inducing embryo are not well understood. Herein we address spatiotemporal development embryonic mouse liver by conditional deletion Apc and β-catenin at different stages development. In normal development, metabolising carbamoylphosphate synthetase I (CPSI) Glutamine (GS) begin to be expressed separate hepatoblasts from E13.5 E15.5...
There have been few studies evaluating the efficacy of knowledge-transfer methods for livestock owners in developing countries, and to authors' knowledge no published work is available that evaluates effect interventions on education working equid users. A cluster-randomised controlled trial (c-RCT) was used evaluate compare effectiveness three knowledge-change about health amongst rural Ethiopian Groups were exposed either; an audio programme, a village meeting or diagrammatic handout, all...
Colorectal cancer (CRC) is the second leading cause of death worldwide and most deaths result from metastases. We have analyzed animal models in which Apc, a gene that frequently mutated during early stages colorectal carcinogenesis, was inactivated human samples to try identify novel potential biomarkers for CRC.We initially compared proteomic transcriptomic profiles small intestinal epithelium transgenic mice Apc and/or Myc had been inactivated. then studied mRNA immunohistochemical...
p53 is an important tumour suppressor with a known role in the later stages of colorectal cancer, but its relevance to early neoplastic initiation remains somewhat unclear. Although p53-dependent regulation Wnt signalling activity occur, importance these regulatory mechanisms during intestinal neoplasia has not been demonstrated.We have conditionally deleted Adenomatous Polyposis coli gene (Apc) from adult murine intestine wild type and deficient environments subsequently compared phenotype...
<h3>Objective</h3> Expression of the Wnt target gene <i>ASCL2</i> is elevated in 78% intestinal neoplasia datasets (Oncomine), suggesting a role for deregulated aetiology tumourigenesis. Furthermore, ectopic expression <i>Ascl2</i> has previously been shown to lead hyperplasia mouse. However, levels does not have an impact on overall survival or recurrence-free rates colorectal cancer patients. Here authors use novel mouse model analyse tumourigenesis and address controversy surrounding...
Conditional deletion of the tumour suppressor gene Apc within murine intestine results in acute Wnt signalling activation. The associated over-expression a myriad target genes yields phenotypic alterations that encompass many hallmarks neoplasia. Previous transcriptomic analysis aimed at identifying potentially play an important role this process, inferred Hormonally upregulated Neu-associated kinase (HUNK/Mak-v/Bstk1) as possible candidate. Hunk is SNF1 (sucrose non fermenting 1)-related...
Abstract The importance of the Wnt-signaling pathway on regulation and maintenance intestinal stem cell (ISC) population is well recognized. However, our current knowledge base founded models using systems gross deregulation pathway. Given this signaling homeostasis, there a need to explore role more subtle alterations in levels within tissue. Herein, we have used model Apc2 loss meet aim. homolog Apc which can also form destruction complex capable binding β-catenin, albeit less efficiently...