High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models.

Unlabelled: BI-847325 is an ATP-competitive inhibitor of MEK/Aurora kinases with the potential to treat a wide range of cancers. In a panel of 294 human tumor cell lines in vitro, BI-847325 was found to be a highly selective inhibitor that was active in the submicromolar range. The most sensitive cancer types were acute lymphocytic and myelocytic leukemia, melanomas, bladder, colorectal, and mammary cancers.

The contribution of family physicians to surgical capacity at district hospitals in South Africa.

The World Health Organization states that essential, cost-effective surgical care should be delivered at district hospitals. In South Africa significant skills gap exist at district hospitals, particularly in the area of surgery and anaesthesia. These small to moderate sized hospitals are too small to support a range of full time specialists even if they could be recruited and were cost-effective.

Pharmacogenomics characterization of the MDM2 inhibitor MI-773 reveals candidate tumours and predictive biomarkers.

MI-773 is a recently developed small-molecule inhibitor of the mouse double minute 2 (MDM2) proto-oncogene. Preclinical data on the anti-tumour activity of MI-773 are limited and indicate that tumour cell lines (CLs) with mutated TP53 are more resistant to MI-773 than wild type TP53. Here, we explored the compound's therapeutic potential in vitro using a panel of 274 annotated CLs derived from a diversity of tumours.

Successful use of an improvised bubble CPAP device for severe respiratory distress caused by pulmonary tuberculosis.

Introduction: This case report discusses the successful use of an improvised bubble continuous positive airway pressure (CPAP) apparatus made using items commonly available in a poorly resourced district hospital.

Case Presentation: A 64-year-old female with no co-morbidities presented with respiratory failure due to pulmonary tuberculosis and was not accepted into the regional Intensive Care Unit (ICU) on referral. She required 8 days of improvised bubble CPAP to maintain adequate oxygen saturation before weaning and eventual discharge.

The role of family physicians in emergency and essential surgical care in the district health system in South Africa.

No abstract available.

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

Background: The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen.

Methods: Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation.

Implementing liquid biopsies into clinical decision making for cancer immunotherapy.

During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies.

Is continuous positive airway pressure a feasible treatment modality for neonates with respiratory distress syndrome in a rural district hospital?

Objectives: To assess the feasibility of using nasal continuous positive airway pressure (nCPAP) in neonates with respiratory distress syndrome at district hospital level by assessing in-hospital survival rates and the impact on transfer rates.

Methods: A prospective database was kept from 2008 to record the outcomes of neonates with mild to moderate respiratory distress treated with nCPAP at a South African rural district hospital. Transfer rates were compared for the two years before and after introduction of neonatal nCPAP using additional retrospective data from the Perinatal Problem Identification Programme (PPIP) for comparison.

EO9 (Apaziquone): from the clinic to the laboratory and back again.

EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v.

Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models.

Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-drug was synthesized (CP-4126), with an elaidic fatty acid esterified at the 5'position.

[Fewer blood transfusions after introduction of auto-transfusion system as part of hip- and knee-replacement surgery].

Objective: To establish the effect of the introduction of an auto-transfusion system on the number of homologous blood transfusions required as part of total hip- and knee-replacement surgery.

Design: Prospective observational study.

Methods: The number of homologous blood transfusions required after total hip or knee replacement was compared between a group of 195 patients before and a group of 176 patients after introduction of an auto-transfusion system.

KML001 cytotoxic activity is associated with its binding to telomeric sequences and telomere erosion in prostate cancer cells.

Purpose: KML001 (sodium metaarsenite) is an orally bioavailable arsenic compound that has entered phase I/II clinical trials in prostate cancer. In this study, we elucidated the mode of action of KML001 and investigated its effects on telomerase and telomeres.

Experimental Design: We compared telomere length to KML001 cytotoxic activity in a panel of human solid tumor cell lines.