Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function.

STUDY QUESTION Are the concentrations of factors secreted by decidual natural killer (dNK) cells from pregnancies at high risk of poor spiral artery remodelling different to those secreted from pregnancies at low risk? SUMMARY ANSWER Expression levels of PLGF, sIL-2R, endostatin and angiogenin were significantly increased by dNK cells from high-risk pregnancies, and angiogenin and endostatin were found to alter trophoblast function. WHAT IS KNOWN ALREADY During early pregnancy, maternal uterine spiral arteries are remodelled from small diameter, low-flow, high-resistance vessels into larger diameter, higher flow vessels, with low-resistance. This change is essential for the developing fetus to obtain sufficient oxygen and nutrients. dNK cells have been implicated in this process. STUDY DESIGN, SIZE, DURATION dNK cells were isolated from first trimester terminations of pregnancies (obtained with local ethical approval) screened for normal- or high-resistance index, indicative of cases least (21%) likely to have developed pre-eclampsia had the pregnancy not been terminated (n = 18 each group). Secreted factors and the effects of these on the trophoblast cell line, SGHPL-4, were assessed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS A multiplex assay was used to assess dNK cell-secreted factors. SGHPL-4 cell functions were assessed using time-lapse microscopy, 3D invasion assays, endothelial-like tube formation ability and western blot analysis. MAIN RESULTS AND THE ROLE OF CHANCE The expression levels of PLGF (P < 0.01), sIL-2R (P < 0.01), endostatin (P < 0.05) and angiogenin (P < 0.05) were significantly increased by dNK cells from high-risk pregnancies. Endostatin significantly decreased SGHPL-4 invasion (P < 0.05), SGHPL-4 tube formation (P < 0.05) and SGHPL-4 Aktser473 phosphorylation (P < 0.05). Angiogenin significantly decreased SGHPL-4 invasion (P < 0.05), but increased SGHPL-4 tube formation (P < 0.01) and decreased SGHPL-4 Aktser473 phosphorylation (P < 0.05). LIMITATIONS, REASONS FOR CAUTION The culture of dNK cells and protein concentrations in vitro may not fully represent the in vivo situation. Although SGHPL-4 cells are extravillous trophoblast derived, further studies would be needed to confirm the roles of angiogenin and endostatin in vivo. WIDER IMPLICATIONS OF THE FINDINGS The altered expression of secreted factors of dNK cells may contribute to pregnancy disorders associated with poor spiral artery remodelling. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Wellcome Trust (project reference 091550). R.F. was a recipient of a PhD studentship from the Division of Biomedical Sciences, St. George's, University of London. The authors have no conflict of interests

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Waste tyre pyrolysis : sustainable recovery and reuse of a valuable resource

End-of-life car passenger tyres represent a major waste management problem, with more than 450,000 tonnes of used tyres being generated each year in the UK alone (approximately 55,000,000 tyres). Recent legislation has made 100% material or value recovery from waste tyres an imperative. There are many different waste tyre management options available. The most commonly used processes include: retreading, use as fuel in incinerators and cement kilns and reprocessing to produce rubber crumb which has further applications in asphalt mixtures, carpet underlay and playgrounds. The theme of the research presented is a fundamental study and development of tyre pyrolysis. Pyrolysis is an attractive method to sustainably recover valuable components of the tyre rubber through the generated carbonaceous solid, oil and gas. Both conventional and microwave-induced pyrolysis have been investigated. Microwave pyrolysis offers an exciting alternative to traditional pyrolysis because of the potentially significant energy efficiency advantage offered. In the first instance an investigation of the optimisation of the pyrolysis conditions by statistical design using conventional means to produce a carbonaceous solid char has been undertaken. This was followed by the investigation of microwave-induced pyrolysis using modified commercially available microwave equipment as well as a bespoke and novel 2450 MHz, 2 kW rotary microwave furnace developed for the purposes of this project by Cobham Microwave Ltd. Carbonaceous solids produced by varying different experimental parameters, such as power levels and pyrolysis duration are reported and analysed. In addition, the main constituents of the oils generated have been identified and comparisons made with traditional thermal pyrolysis oil. Reuse of the solid residue is an important activity which has been researched. This char is often described as carbon black, but given that it contains all the solid, inorganic components present in the tyre, as well as carbon black, it is better described as “char filler”. The suitability of this waste tyre-derived char for reuse in the rubber industry as a filler substitute has been evaluated and is presented. The results show that the char has similar properties to a semi-reinforcing filler with potential for improvement.Open Acces

Carboplatin, vinblastine and mitomycin-C in the treatment of non-small cell bronchogenic carcinoma

Thirty patients with advanced non-small cell lung carcinoma were treated with carboplatin, vinblastine and mitomycin-C. Objective tumor regression was noted in 6 patients. Toxicity of this combination was moderate