Phase II study of CC-486 (oral azacitidine) in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma

BACKGROUND: Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. PATIENTS AND METHODS: Patients with locally advanced or metastatic NPC and 1-2 prior treatment regimens received CC-486 300 mg daily on days 1-14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. RESULTS: Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status 64 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. CONCLUSION: CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours

Biotic communities of freshwater marshes and mangroves in relation to saltwater incursions: implications for wetland regulation

An ecosystem-level study was conducted in the Guandu wetlands in subtropical coastal Taiwan to examine how salinity influences the abundance, diversity, and structure of biotic communities. We surveyed eight permanent study sites, spanning freshwater marshes, to the gate on the dyke, and mesohaline mangroves representing a gradient of the extent of saltwater incursions. Analyses of abiotic variables showed that salinity was the primary determining factor for discriminating habitat types in the wetlands, but communities differed in their sensitivity to salinity. The composition of plant and insect communities was most affected by the salinity gradient, suggesting the utility of these communities for ecological monitoring of saltwater incursions. However, spatial changes in communities at higher trophic levels, including macrobenthos, mollusks, fish, and birds, could not be explained simply by the salinity gradient. Instead, changes in these communities were more relevant to the composition of other biotic communities. Our results show that species richness and diversity of plant communities were higher in the marshes than in the mangroves. Nevertheless, insect communities censused in the mangroves had higher diversity, despite lower abundance and species richness. Macrobenthos surveyed in the mangroves showed higher biomass and number of taxa. Mollusks and fish were also more abundant at sites near the gate compared to the marsh sites. This suggests that maintaining a tidal flux by means of gate regulation is necessary for conserving the spatial heterogeneity and biodiversity of coastal wetlands

Sparticle masses in deflected mirage mediation

We discuss the sparticle mass patterns that can be realized in deflected mirage mediation scenario of supersymmetry breaking, in which the moduli, anomaly, and gauge mediations all contribute to the MSSM soft parameters. Analytic expression of low energy soft parameters and also the sfermion mass sum rules are derived, which can be used to interpret the experimentally measured sparticle masses within the framework of the most general mixed moduli-gauge-anomaly mediation. Phenomenological aspects of some specific examples are also discussed.Comment: 43 pages, 17 figures, references adde

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Mouse Chromosome 11

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46996/1/335_2004_Article_BF00648429.pd

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Establishment of activity indicator of TiO2 photocatalytic reaction-Hydroxyl radical trapping method

In this study, a new, low cost and easy method, hydroxyl radical trapping method, was employed to investigate the photo-activity of UV/TiO2 photocatalytic reaction. The Taguchi method was utilized to optimize the preparation of titanium dioxide (TiO2) thin-film reactor through the modified chemical vapor deposition (CVD) method. The optimal yield of hydroxyl radicals was then evaluated by calculating the conversion ratio of salicylic acid under the optimal conditions. in the experiments, salicylic acid was used as the free-radical scavenger and the formation of three different intermediates were examined to shed light on the trend and kinetics of reaction of hydroxyl radical with organic substance under different operation conditions. The results indicated that the yield of hydroxyl radicals increased with increasing irradiation intensity and dissolved oxygen level. The optimal experimental conditions obtained in this study were irradiation with intensity of 2.9 mW cm(-2) on salicylic acid at concentration of 250 mg L-1 by both agitation and aeration processes (dissolved oxygen level = 8.2 mg O-2 L-1) at pH 5. Such conditions could achieve the optimal hydroxyl radical yield of 5.1 x 10(-17) M. (C) 2008 Elsevier B.V. All rights reserve

Optimizing preparation of the TiO2 thin film reactor using the Taguchi method

In this study, titanium dioxide thin film was prepared using the modified chemical vapor deposition. The parameters employed to control the preparation of the catalyst include the temperature of water bath, the Ti(OC3H7)(4)/H2O ratio, the flow rate of carrier gas, the oxidation temperature, the oxidation time, the calcination temperature, the rotating speed of furnace, and the speed of geared motor. The orthogonal arrays in the design of experimental method proposed by Taguchi were adopted to conduct the multiplefactor experiment. The conversion rate of salicylic acid in the aqueous or heterogeneous phase photocatalysis experiment was employed to identify the optimal conditions for assembly. The results indicated that a higher conversion ratio of the organic substance could be achieved under catalytic oxidation temperature of 400 degrees C, calcination temperature of 550 degrees C, and spraying speed of 30 rpm and the optimal experimental conditions obtained in this study were irradiation with intensity of 2.9 MW cm(-2) on salicylic acid at concentration of 250 mg L-1 by both agitation and aeration processes (dissolved oxygen level = 8.2 Mg O-2 L-1) at pH 5, which could achieve optimal hydroxyl radical yield of 5.1 X 10(-17) M. (C) 2009 Elsevier Ltd. All rights reserved

Effect of pH on Fenton process using estimation of hydroxyl radical with salicylic acid as trapping reagent

This study estimates the yield of hydroxyl radical using salicylic acid as the trapping reagent and investigates the relationship between hydroxyl radical and pH value. The formation and variation of hydroxyl radical under different pH values were evaluated using reaction products, 2,3-DHBA, 2,5-DHBA, and catechol. The formation rate of hydroxyl radical was dependent on the ratio of ferrous ion to hydrogen peroxide and pH values. The difference between various pH values was explored. The kinetics and mechanisms of hydroxyl radical reactions were established in the Fenton process. Experimental results showed that the best reaction conditions were 8.5mM H(2)O(2), 1.25mM Fe(2+), Fe(2+)/H(2)O(2) = 0.147 at pH 3 and the formation rate constant of hydroxyl radical was 1.12 x 10(11) M(-1)s(-1)

Comparison between two different methods of immobilizing NGF in poly(DL-lactic acid-co-glycolic acid) conduit for peripheral nerve regeneration by EDC/NHS/MES and genipin

For surface modification and nerve regeneration, chitosan, followed by nerve growth factor (NGF), was immobilized onto the interior surface of poly (lactic acit-co-glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP). Four new conduits were, therefore, obtained and named by immobilizing order-EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were evaluated and compared, respectively. The researchers found that the EDCs- and GP-cross-linked chitosan displayed higher hydrophilic than pure poly (DL-lactic acid-co-glycolic acid) (PLGA) in water contact angle experiment, which meant the cell compatibility was improved by the modification. Scanning electron microscopic observations revealed that the GP-cross-linking of chitosan greatly improved cell compatibility while cultured rat PC12 cells were flatter and more spindle-shaped than EDCs-cross-linked chitosan. The results concerning the GP-crosslinked chitosan revealed significant proliferation of the seeded cells relative to pure PLGA films, as determined by counting cells and MTT assay. The NGF was released from the modified conduits in two separate periods-an initial burst in 5 days and then slow release from day 10 to day 40. The GP/EDCs group had the highest NGF value among all groups after the 5th day. Finally, the controlled-release conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks following implantation, morphological analysis revealed the highest numbers of myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group. Therefore, the results confirm that GP/EDCs groups with good cell compatibility and effective release of NGF can considerably improve peripheral nerve regeneration. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 576-585, 2011