Characteristics and attitudes of first round invitees in the Irish National Colorectal Cancer Screening Programme.

Background/objective: Colorectal cancer (CRC) screening is proven to reduce CRC-related mortality. Faecal immunochemical testing (FIT)-positive clients in the Irish National CRC Screening Programme underwent colonoscopy. Round 1 uptake was 40.

Aging and ocular tissue stiffness in glaucoma.

Glaucoma is a progressive and chronic neurodegenerative disorder characterized by damage to the inner layers of the retina and deformation of the optic nerve head. The degeneration of retinal ganglion cells and their axons results in an irreversible loss of vision and is correlated with increasing age. Extracellular matrix changes related to natural aging generate a stiffer extracellular environment throughout the body.

Establishment of a national cervical screening programme in Ireland, CervicalCheck: the first 6 years.

The national cervical screening programme, CervicalCheck, commenced in Ireland in 2008. Free cervical smear tests are offered to over 1.2 million women aged 25-60 every 3 (aged 25-44) and 5 (aged 45-60) years.

Using 3D Culture of Primary Mammary Epithelial Cells to Define Molecular Entities Required for Acinus Formation: Analyzing MAP Kinase Phosphatases.

Three-dimensional (3D) cell cultures on reconstituted basement membrane (rBM) enable the study of complex interactions between extracellular matrix (ECM) components and epithelial cells, which are crucial for the establishment of cell polarity and functional development of epithelia. 3D cultures of mammary epithelial cells (MECs) on Matrigel (a laminin-rich ECM derived from the Engelbreth-Holm-Swarm (EHS) murine tumor) promote interactions of MECs with the matrix via integrins, leading to formation of spherical monolayers of polarized cells surrounding a hollow lumen (acini). Acini closely resemble mammary alveoli found in the mammary gland.

Overview of Mammary Gland Development: A Comparison of Mouse and Human.

The mouse mammary gland is widely used as a model for human breast cancer and has greatly added to our understanding of the molecular mechanisms involved in breast cancer development and progression. To fully appreciate the validity and limitations of the mouse model, it is essential to be aware of the similarities and also the differences that exist between the mouse mammary gland and the human breast. This introduction therefore describes the parallels and contrasts in mouse mammary gland and human breast morphogenesis from an early embryonic phase through to puberty, adulthood, pregnancy, parturition, and lactation, and finally the regressive stage of involution.

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Background: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma.

Metabolomics/Proteomics strategies used to identify biomarkers for exfoliation glaucoma.

It is currently estimated that 60 to 70 million people worldwide are affected by open-angle glaucoma and the majority of patients who present to clinic have raised intraocular pressure, visual field loss, and cupping of the optic nerve. Although exfoliation glaucoma (XFG) correlates with age, it is the most common cause of secondary open-angle glaucoma in the world and, with elevated intraocular pressure at onset, this disease runs an aggressive clinical course. XFG differs from primary open-angle glaucoma, in that patients have a diminished response to medication, show accelerated rates of disease progression, and therefore have a higher need for surgery.

miR-187 is an independent prognostic factor in breast cancer and confers increased invasive potential in vitro.

Purpose: Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression.

Experimental Design: Coinertia analysis (CIA) was used to combine a database of predicted miRNA target sites and gene expression data. Using two independent breast cancer cohorts, CIA was combined with correspondence analysis and between group analysis to produce a ranked list of miRNAs associated with disease progression.

c-Jun N-terminal kinase activity supports multiple phases of 3D-mammary epithelial acinus formation.

Primary murine mammary epithelial cells cultured on a laminin-rich-extracellular matrix (ECM) require c-Jun N-terminal kinase (JNK) activity for acinus formation. Inhibition of JNK (using SP600125) or small interfering RNA-mediated knockdown of JNK1 blocked acinus formation, impaired cell polarisation and lumen clearance and allowed sustained extracellular signal-regulated kinase (ERK) phosphorylation, cell proliferation, adhesion-independent cell survival and expression of epithelial-mesenchymal transition markers. ERK inhibition abolished the effects of JNK blockade.

Molecular regulators of pubertal mammary gland development.

The pubertal mammary gland is an ideal model for experimental morphogenesis. The primary glandular branching morphogenesis occurs at this time, integrating epithelial cell proliferation, differentiation, and apoptosis. Between birth and puberty, the mammary gland exists in a relatively quiescent state.

PKCzeta regulates cell polarisation and proliferation restriction during mammary acinus formation.

Mammary epithelial cells organize in three dimensions and generate acini when supported on laminin-rich extracellular matrix. Acinus formation begins with the apicobasal polarisation of the outer cells of the assembly and the withdrawal of these cells from the cell cycle. Internal cells then clear out to form a hollow lumen.

Cyclin D1b in human breast carcinoma and coexpression with cyclin D1a is associated with poor outcome.

Background/aim: Cyclin D1 is a mediator of cell-cycle control that is frequently overexpressed in primary ductal breast carcinomas, but its role is controversial. A polymorphism in the CCND1 gene, G870A, results in an aberrantly spliced protein (cyclin D1b) lacking the Thr-286 phosphorylation site necessary for nuclear export. Studies of murine fibroblasts have shown that although overexpression of canonical cyclin D1 (cyclin D1a) alone is not sufficient to drive malignant transformation, expression of nuclear cyclin D1b is oncogenic.

Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development.

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important.

Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach.

Background & Aims: The epithelial zinc-finger transcription factor Klf4 (formerly GKLF) regulates cellular proliferation and differentiation in vitro. Klf4 null mice die by postnatal day 1 and show changes in epithelial differentiation of skin and colon.

Methods: We used tissue-specific gene ablation to generate mice lacking Klf4 in their gastric epithelia.

Of mice and MEN1: Insulinomas in a conditional mouse knockout.

Patients with multiple endocrine neoplasia type 1 (MEN1) develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and endocrine pancreas, due to the inactivation of the MEN1 gene. A conditional mouse model was developed to evaluate the loss of the mouse homolog, Men1, in the pancreatic beta cell. Men1 in these mice contains exons 3 to 8 flanked by loxP sites, such that, when the mice are crossed to transgenic mice expressing cre from the rat insulin promoter (RIP-cre), exons 3 to 8 are deleted in beta cells.