Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α.

Junction-mediating and regulatory protein (JMY) is a novel p53 cofactor that regulates p53 activity during stress. JMY interacts with p300/CBP, which are ubiquitous transcriptional co-activators that interact with a variety of sequence-specific transcription factors, including hypoxia-inducible factor-1α (HIF-1α). In addition, JMY is an actin-nucleating protein, which, through its WH2 domains, stimulates cell motility. In this study, we show that JMY is upregulated during hypoxia in a HIF-1α-dependent manner. The JMY gene contains HIF-responsive elements in its promoter region and HIF-1α is recruited to its promoter during hypoxia. HIF-1α drives transcription of JMY, which accounts for its induction under hypoxia. Moreover, the enhanced cell motility and invasion that occurs during hypoxia requires JMY, as depleting JMY under hypoxic conditions causes decreased cell motility. Our results establish the interplay between JMY and HIF-1α as a new mechanism that controls cell motility under hypoxic stress

PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic cancer

pancreatic cance

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer

© 2018 Cancer Research UK. Background: Metastatic spread is responsible for the majority of cancer-associated deaths. The tumour microenvironment, including hypoxia, is a major driver of metastasis. The aim of this study was to investigate the role of the E3 ligase WSB-1 in breast cancer biology in the context of the hypoxic tumour microenvironment, particularly regarding metastatic spread. Methods: In this study, WSB-1 expression was evaluated in breast cancer cell lines and patient samples. In silico analyses were used to determine the impact of WSB-1 expression on distant metastasis-free survival (DMFS) in patients, and correlation between WSB1 expression and hypoxia gene expression signatures. The role of WSB-1 on metastasis promotion was evaluated in vitro and in vivo. Results: High WSB1 expression was associated with decreased DMFS in ER-breast cancer and PR-breast cancer patients. Surprisingly, WSB1 expression was not positively correlated with known hypoxic gene expression signatures in patient samples. Our study is the first to show that WSB-1 knockdown led to decreased metastatic potential in breast cancer hormone receptor-negative models in vitro and in vivo. WSB-1 knockdown was associated with decreased metalloproteinase (MMP) activity, vascular endothelial growth factor (VEGF) secretion, and angiogenic potential. Conclusions: Our data suggests that WSB-1 may be an important regulator of aggressive metastatic disease in hormone receptor-negative breast cancer. WSB-1 could therefore represent a novel regulator and therapeutic target for secondary breast cancer in these patients

Location of residence associated with the likelihood of patient visit to the preoperative assessment clinic

BACKGROUND: Outpatient preoperative assessment clinics were developed to provide an efficient assessment of surgical patients prior to surgery, and have demonstrated benefits to patients and the health care system. However, the centralization of preoperative assessment clinics may introduce geographical barriers to utilization that are dependent on where a patient lives with respect to the location of the preoperative assessment clinic. METHODS: The association between geographical distance from a patient's place of residence to the preoperative assessment clinic, and the likelihood of a patient visit to the clinic prior to surgery, was assessed for all patients undergoing surgery at a tertiary health care centre in a major Canadian city. The odds of attending the preoperative clinic were adjusted for patient characteristics and clinical factors. RESULTS: Patients were less likely to visit the preoperative assessment clinic prior to surgery as distance from the patient's place of residence to the clinic increased (adjusted OR = 0.52, 95% CI 0.44–0.63 for distances between 50–100 km, and OR = 0.26, 95% CI 0.21–0.31 for distances greater than 250 km). This 'distance decay' effect was remarkable for all surgical specialties. CONCLUSION: The present study demonstrates that the likelihood of a patient visiting the preoperative assessment clinic appears to depend on the geographical location of patients' residences. Patients who live closest to the clinic tend to be seen more often than patients who live in rural and remote areas. This observation may have implications for achieving the goals of equitable access, and optimal patient care and resource utilization in a single universal insurer health care system