The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC50 = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC50 = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

Acute myocardial infarction: The spouse's experience

Given the marked changes in length of hospital stay and the number of CAB procedures being performed, it is essential that health professionals are aware of the potential impact these changes could have on the spouses of patients who have undergone CAB surgery. Results from numerous quantitative studies suggest that spouses of patients undergoing CAB surgery experience both physical and emotional stress before and after their partners surgery. While such studies have contributed to our understanding, they fail to capture the qualitative experience of what it is like to be a spouse of a partner who has undergone CAB surgery, specifically in the context of changes in the length of hospital stay. The objective of this study was to describe the experience of spouses of patients who had recently undergone CAB surgery. This study utilised a qualitative methodology and was guided by Husserl's phenomenological approach. Data was obtained from four participants by in depth open ended interviews. This study has implications for all health professionals involved in the care of patients and their families undergoing CAB surgery. If health professionals are to provide holistic care, they need to understand more fully the qualitative experience of spouses of critically ill patients. The purpose of this study was to describe the experience of spouses whose partner's had suffered an acute myocardial infarction (MI). The study was guided by a phenomenological approach. This qualitative type of study is new to nursing inquiry, therefore this investigation creates links with understanding the notion of psychosocial nursing processes with the leading cause of death in Australia. Literature concerning the spouses of myocardial infarction patients has predominantly employed quantitative methods, as such results have centred on structured data collection, and categorised outcomes. Such methods have failed to capture the insight of what it is like to be a spouse of a patient who has had an MI. In-depth interviews were conducted with three participants (2 females and 1 male) about their experiences. The major findings of the study were categorised under the headings of uncertainty, emotional turmoil, support information and lifestyle change. Conclusions suggest that spouses are neglected by health professionals and they require as much psychosocial support as their partner in terms of cardiac discharge planning. Spouses need to be granted special consideration, as they progress through a grieving and readjustment process in coming to terms with: (1) the need to support and care for their partner, (2) changes in their roles and (3) adjustments to their current lifestyles.

Assessment of the severity of Ebola virus disease in Sierra Leone in 2014–2015

The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6–75·5] and 68·9% (95% CrI 66·2–71·6), respectively. Risks of death were higher in the youngest (0–4 years) and oldest (≥60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone.

Determination of the kallikrein-related peptidase 7 degradome and Transciptome in ovarian cancer

Ovarian cancer is the leading cause of cancer-related death in women, and the need for curative treatments is urgent. This study characterised an enzyme associated with the most lethal form of ovarian cancer, showing this enzyme to be a promising therapeutic target. Fifteen novel protein targets and key signalling pathways were determined to be regulated by this enzyme, kallikrein-related peptidase 7, in the ovarian tumour microenvironment, highlighting its involvement in cancer progression. Inhibition of this enzyme may be a useful therapeutic option to improve the life expectancy of women suffering from this cancer.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.