Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer

Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m−2 was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m−2 was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3–4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3–4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9–36%). Median response duration was 31 weeks (range 11–83 weeks) and median survival time 31 weeks (range 2–171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity. © 1999 Cancer Research Campaig

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

Linda Flinterman and colleagues report on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event

Validity of claims made in weight management research: a narrative review of dietetic articles

<p>Abstract</p> <p>Background</p> <p>The best available evidence demonstrates that conventional weight management has a high long-term failure rate. The ethical implications of continued reliance on an energy deficit approach to weight management are under-explored.</p> <p>Methods</p> <p>A narrative literature review of journal articles in <it>The Journal of Human Nutrition and Dietetics </it>from 2004 to 2008.</p> <p>Results</p> <p>Although the energy deficit approach to weight management has a high long-term failure rate it continues to dominate research in the field. In the current research agenda, controversies and complexities in the evidence base are inadequately discussed, and claims about the likely success of weight management misrepresent available evidence.</p> <p>Conclusions</p> <p>Dietetic literature on weight management fails to meet the standards of evidence based medicine. Research in the field is characterised by speculative claims that fail to accurately represent the available data. There is a corresponding lack of debate on the ethical implications of continuing to promote ineffective treatment regimes and little research into alternative non-weight centred approaches. An alternative health at every size approach is recommended.</p

Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

Tumour angiogenesis and the levels of plasminogen activator inhibitor type I (PAI-I) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-I has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-I level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley counting technique. The levels of PAI-I and its target proteinase uPA in tumour extracts were analysed by ELISA. The Chalkley count was not correlated with the levels of uPA or PAI-I. High values of uPA, PAI-I, and Chalkley count were all significantly correlated with a shorter recurrence-free survival and overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-I level and the Chalkley count, with a hazard ratio (95% CI) of 1.6 (1.01-2.69) and 1.4 (1.02-1.81), respectively. For overall survival, the Chalkley count, but not PAI-I, was of significant independent prognostic value. The risk of death was 1.7 (1,30-2.15) for Chalkley counts in the upper tertile compared to the lower one. We conclude that the PAI-I level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-I is not only based on its involvement in angiogenesis. (C) 2003 Cancer Research UK

Optical Coherence Tomography in the UK Biobank Study – Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

Purpose: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. Methods: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. Results: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. Conclusions: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging

Intratumoral heterogeneity of microRNA expression in rectal cancer

Introduction: An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods: The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman's correlation. Results: ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion: Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630. Interestingly, we found a poor correlation between the expression estimates obtained by RT-qPCR and ISH, respectively

Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study

We analysed the relation between adult breast cancer risk and adiposity in ages 8–25, and among 90 509 women included in the E3N cohort study, and investigated the potential modification effect of certain factors. Participants completed a questionnaire that included a set of eight silhouettes corresponding to body shape at different ages. During the follow-up (mean=11.4 years), 3491 breast cancer cases were identified. Negative trends in risk of breast cancer with increasing body silhouettes at age 8 and at menarche were observed, irrespective of menopausal status, with relative risks of 0.73 (0.53–0.99) and 0.82 (0.66–1.02) for women who reported a silhouette equal or greater than the fifth silhouette at age 8 and at menarche, respectively. We observed no clear effect modification by age at menarche, delay between age at menarche, regular cycling, regularity of cycles in adult life or body mass index at baseline

Biorefining of wheat straw:accounting for the distribution of mineral elements in pretreated biomass by an extended pretreatment–severity equation

BACKGROUND: Mineral elements present in lignocellulosic biomass feedstocks may accumulate in biorefinery process streams and cause technological problems, or alternatively can be reaped for value addition. A better understanding of the distribution of minerals in biomass in response to pretreatment factors is therefore important in relation to development of new biorefinery processes. The objective of the present study was to examine the levels of mineral elements in pretreated wheat straw in response to systematic variations in the hydrothermal pretreatment parameters (pH, temperature, and treatment time), and to assess whether it is possible to model mineral levels in the pretreated fiber fraction. RESULTS: Principal component analysis of the wheat straw biomass constituents, including mineral elements, showed that the recovered levels of wheat straw constituents after different hydrothermal pretreatments could be divided into two groups: 1) Phosphorus, magnesium, potassium, manganese, zinc, and calcium correlated with xylose and arabinose (that is, hemicellulose), and levels of these constituents present in the fiber fraction after pretreatment varied depending on the pretreatment-severity; and 2) Silicon, iron, copper, aluminum correlated with lignin and cellulose levels, but the levels of these constituents showed no severity-dependent trends. For the first group, an expanded pretreatment-severity equation, containing a specific factor for each constituent, accounting for variability due to pretreatment pH, was developed. Using this equation, the mineral levels could be predicted with R(2) > 0.75; for some with R(2) up to 0.96. CONCLUSION: Pretreatment conditions, especially pH, significantly influenced the levels of phosphorus, magnesium, potassium, manganese, zinc, and calcium in the resulting fiber fractions. A new expanded pretreatment-severity equation is proposed to model and predict mineral composition in pretreated wheat straw biomass