| Nature Publishing Group Ids | Title | Abstract | Authors | Journal | Publication Date | Product Version |
|---|---|---|---|---|---|---|
| naturepublishinggroup10.1038/nature10810 | The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila | Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly population. Ageing is one of the most prominent factors to influence disease onset and progression1, yet little is known about the molecular pathways that connect these processes. To understand this connection it is necessary to identify the pathways that functionally integrate ageing, chronic maintenance of the brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as critical factors in gene regulation during development; however, their role in adult-onset, age-associated processes is only beginning to be revealed. Here we report that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched and age-modulated characteristics. Whereas mir-34 loss triggers a gene profile of accelerated brain ageing, late-onset brain degeneration and a catastrophic decline in survival, mir-34 upregulation extends median lifespan and mitigates neurodegeneration induced by human pathogenic polyglutamine disease protein. Some of the age-associated effects of miR-34 require adult-onset translational repression of Eip74EF, an essential ETS domain transcription factor involved in steroid hormone pathways. Our studies indicate that miRNA-dependent pathways may have an impact on adult-onset, age-associated events by silencing developmental genes that later have a deleterious influence on adult life cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this process. | [Nan Liu, Michael Landreh, Kajia Cao, Masashi Abe, Gert-Jan Hendriks, Jason R. Kennerdell, Yongqing Zhu, Li-San Wang, Nancy M. Bonini] | Nature | 2012-02-15 | |
| naturepublishinggroup10.1038/bjc.2012.7 | Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules | [T Shimokawa, M Seike, C Soeno, H Uesaka, A Miyanaga, H Mizutani, K Kitamura, Y Minegishi, R Noro, T Okano, A Yoshimura, A Gemma] | British Journal of Cancer | 2012-02-14 |
| PubMed Ids | Title | Abstract | Authors | Journal | Publication Date | Product Version |
|---|---|---|---|---|---|---|
| pubmed22487523 | Invasive markers identified by gene expression profiling in pancreatic cancer. | Molecular profiling has proven utility as a diagnostic and predictive tool in clinical oncology. However, a clinically relevant gene expression profile in pancreatic cancer remains elusive. Primary and metastatic pancreatic cancer cell lines (BxPC-3 and AsPC-1), were stimulated with phorbol-12-myristate 13-acetate (PMA), a known inducer of cell invasion. Affymetrix gene expression microarray analysis was performed, comparing gene expression to unstimulated controls. Differential expression was identified using ArrayAssist, and confirmed using quantitative real-time PCR. Bioinformatic analysis was performed using Pathway Studio and GOstat. The derived gene expression was further validated in fresh frozen pancreatic tumour samples. The ability of the derived 3 gene expression markersto differentiate between pancreatic adenocarcinoma (PDAC) and other neoplasms, and its association with clinicopathological variables was examined. PMA-induced significant changes in cell line gene expression, from which distinctive 3 potential invasive markers were derived. Expression of these genes, uPA, MMP-1 and IL1-R1 was confirmed in human pancreatic tumours, and was found to differentiate PDAC from other pancreatic neoplasms. The expression of IL1-R1 in PDAC is a novel finding. We found that the expression of MMP-1 was associated with high-grade PDAC (p�=�0.035, Wilcoxon rank sum). We have identified three potential invasive markers, uPA, MMP-1 and IL1-R1, whose gene expression may differentiate PDAC from other pancreatic neoplasms, and potentially reflect a more invasive phenotype. | [Rogers A, Smith M J, Doolan P, Clarke C, Clynes M, Murphy J F, McDermott A, Swan N, Crotty P, Ridgway P F, Conlon K C] | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] | 2012-Mar |
