Direct dehydration of 1,3-butanediol into butadiene over aluminosilicate catalysts

The catalytic dehydration of 1,3-butanediol into butadiene was investigated over various aluminosilicates with different SiO2/Al2O3 ratios and pore architectures. A correlation between the catalytic performance and the total number of acid sites and acid strength was established, with a better performance for lower acid site densities as inferred from combined NH3-TPD, pyridine adsorption and 27Al-NMR MAS spectroscopy. The presence of native Brønsted acid sites of medium strength was correlated to the formation of butadiene. A maximum butadiene yield of 60% was achieved at 300 °C over H-ZSM-5 with a SiO2/Al2O3 ratio of 260 with the simultaneous formation of propylene at a BD/propylene selectivity ratio of 2.5. This catalyst further exhibited a slight deactivation during a 102 h run with a decrease in the conversion from 100% to 80% due to coke deposition as evidenced by XPS and TGA-MS, resulting in a 36% loss of the specific surface area

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

Breast Cancer in Young Women: Poor Survival Despite Intensive Treatment

The general aim of the thesis was to gain increased insight into the long-term prognosis for young women with breast cancer. In a population-based cohort of 22,017 women with breast cancer, we studied prognosis by age. Women aged <35 (n=471), 35–39 (n=858) and 40–49 (n=4789) were compared with women aged 50–69. The cumulative 5-year relative survival ratio (RSR) and the relative excess risk (RER) of mortality were calculated. Women <35 years of age had a worse survival than middle-aged women, partly explained by a later stage at diagnosis. After correction for stage, tumor characteristics and treatment, young age remained an independent risk factor for death. The excess risk of death in young women was only present in stage I-II disease and was most pronounced in women with small tumors. For in-depth studies on a large subpopulation from the original cohort (all 471 women aged <35 and a random sample of 700 women aged 35–69), we collected detailed data from the medical records, re-evaluated slides and produced TMAs from tumor tissue. Breast cancer- specific survival (BCSS), distant disease-free survival (DDFS) and locoregional recurrence- free survival (LRFS) by age were analysed. In a multivariate analysis, age <35 and age 35– 39 years conferred a risk in LRFS but not in DDFS and BCSS. The age-related differences in prognosis were most pronounced in early stage luminal Her2-negative tumors, where low age was an independent prognostic factor also for DDFS (HR 1.87 (1.03–3.44)). To study the importance of proliferation markers for the long-term prognosis in young women, protein expression of Ki-67, cyclin A2, B1, D1 and E1 was analysed in 504 women aged <40 and in 383 women aged ≥40. The higher expression of proliferation markers in young women did not have a strong impact on the prognosis. Proliferation markers are less important in young women, and Ki-67 was prognostic only in young women with Luminal PR+ tumors. Age <40 years was an independent risk factor of DDFS exclusively in this subgroup (adjusted HR 2.35 (1.22-4.50)). The only cyclin adding prognostic value beyond subtype in young women was cyclin E1. In a cohort of 469 women aged <40 and 360 women aged ≥40 we examined whether Her2 status assessed by silver enhanced in situ hybridization (SISH) for all cases, would reveal a proportion of women undiagnosed by routine Her2 testing and whether this would affect their prognosis. With SISH testing for all women, the Her2-positive rate increased from 20.0% to 24.4% (p<0.001), and similarly for women aged <40 and ≥40 years. Young women had Her2+ breast cancer twice as often as middle-aged women. Her2 amplification was present in 4.6% of cases scored 0 with IHC, while the corresponding proportions for scores 1+, 2+ and 3+ were 36.0%, 83.7% and 96.8%, respectively. All Her2 amplified cases, both true positive and false negative, had a significantly worse BCSS than the true negative cases

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Electrophysiology of the intrinsic sinus node dysfunction

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Electrophysiologic effects of intravenous xamoterol in patients with sinus node dysfunction

The electrophysiologic effects of xamoterol were studied in ten patients with electrophysiologic evidence of sinus node dysfunction. A significant shortening of mean sinus cycle length, maximal corrected sinus-node recovery time, and the mean of the three longest corrected sinus-node recovery times was observed after intravenous administration of 0.1 mg/kg of xamoterol. The atrioventricular (AV) conduction time and the effective and functional refractory periods of the AV node were shortened as the effective refractory period of the atrium. These effects suggest that xamoterol could be tried safely for the treatment of patients with moderate symptoms due to sinus-node disease. © 1990 Kluwer Academic Publishers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

«A highly active and selective Pd/CeO₂ catalyst for direct amination of alcohols»

National audienc