56 research outputs found

    Differences in the microbial profiles of early stage endometrial cancers between Black and White women

    Get PDF
    Objective: Black women suffer a higher mortality from endometrial cancer (EC) than White women. Potential biological causes for this disparity include a higher prevalence of obesity and more lethal histologic/molecular subtypes. We hypothesize that another biological factor driving this racial disparity could be the EC microbiome. Methods: Banked tumor specimens of postmenopausal, Black and White women undergoing hysterectomy for early stage endometrioid EC were identified. The microbiota of the tumors were characterized by bacterial 16S rRNA sequencing. The microbial component of endometrioid ECs in The Cancer Genome Atlas (TCGA) database were assessed for comparison. Results: 95 early stage ECs were evaluated: 23 Black (24%) and 72 White (76%). Microbial diversity was increased (p < 0.001), and Firmicutes, Cyanobacteria and OD1 phyla abundance was higher in tumors from Black versus White women (p < 0.001). Genus level abundance of Dietzia and Geobacillus were found to be lower in tumors of obese Black versus obese White women (p < 0.001). Analysis of early stage ECs in TCGA found that microbial diversity was higher in ECs from Black versus White women (p < 0.05). When comparing ECs from obese Black versus obese White women, 5 bacteria distributions were distinct, with higher abundance of Lactobacillus acidophilus in ECs from Black women being the most striking difference. Similarly in TCGA, Dietzia and Geobacillus were more common in ECs from White women compared to Black. Conclusion: Increased microbial diversity and the distinct microbial profiles between ECs of obese Black versus obese White women suggests that intra-tumoral bacteria may contribute to EC disparities and pathogenesis

    A century of trends in adult human height

    No full text
    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

    Quality of life endovascular and open AAA repair. Results of a randomised trial.

    No full text
    Contains fulltext : 57956.pdf (publisher's version ) (Closed access)AIM: To compare the quality of life (QoL) in the first postoperative year after elective endovascular abdominal aortic aneurysm repair (EVAR) and open repair (OR) in a randomised study. METHODS: In the Dutch Randomised Endovascular Aneurysm Management (DREAM) trial, patients are randomly allocated to EVAR or OR. QoL questionnaires (SF-36 and EuroQoL-5D) were sent to all patients preoperatively (PREOP) and at five time points in the first postoperative year (3W, 6W, 3M, 6M and 12M). Between November 1999 and August 2002, 153 patients (141 male; 12 female) were randomised (78 EVAR and 75 OR; one crossover from OR to EVAR). The EuroQoL-5D scores and the eight domains of the SF-36 for the two groups were compared using the Mann-Whitney test. Changes over time were analysed using the Wilcoxon sign test. RESULTS: There were no statistically significant differences in baseline characteristics (age, gender and SVS risk factors). The preoperative QoL scores of the study group were similar to the QoL scores of the general population of the same age. After 3W the OR group showed a significant decrease on the EuroQol-5D (p=0.022) and in six of the eight SF-36 domains. The EVAR group also showed a significant decrease on the EuroQol-5D (p=0.004) and in 5 of the 8 domains of the SF-36. At 6W the EuroQol-5D had recovered to baseline in the OR group and the decreased domains of the SF-36 had partially recovered. In the EVAR group the EuroQol-5D and three of the five decreased SF-36 domains, had returned to baseline. From 6M on, the OR group reported a significantly higher score on the EuroQoL-5D than the EVAR group (p=0.045 (6M) and p=0.001 (12M)). CONCLUSION: In the early postoperative period there is a small, yet significant QoL advantage for EVAR compared to OR. At 6 months and beyond, patients reported better QoL after OR than after EVAR

    Mapping the regulatory sequences controlling 93 breast cancer-associated miRNA genes leads to the identification of two functional promoters of the Hsa-mir-200b cluster, methylation of which is associated with metastasis or hormone receptor status in adva

    Get PDF
    MicroRNAs (miRNAs) are small non-coding RNAs of similar to 20 nt in length that are capable of modulating gene expression post-transcriptionally. Although miRNAs have been implicated in cancer, including breast cancer, the regulation of miRNA transcription and the role of defects in this process in cancer is not well understood. In this study we have mapped the promoters of 93 breast cancer-associated miRNAs, and then looked for associations between DNA methylation of 15 of these promoters and miRNA expression in breast cancer cells. The miRNA promoters with clearest association between DNA methylation and expression included a previously described and a novel promoter of the Hsa-mir-200b cluster. The novel promoter of the Hsa-mir-200b cluster, denoted P2, is located similar to 2 kb upstream of the 5' stemloop and maps within a CpG island. P2 has comparable promoter activity to the previously reported promoter (P1), and is able to drive the expression of miR-200b in its endogenous genomic context. DNA methylation of both P1 and P2 was inversely associated with miR-200b expression in eight out of nine breast cancer cell lines, and in vitro methylation of both promoters repressed their activity in reporter assays. In clinical samples, P1 and P2 were differentially methylated with methylation inversely associated with miR-200b expression. P1 was hypermethylated in metastatic lymph nodes compared with matched primary breast tumours whereas P2 hypermethylation was associated with loss of either oestrogen receptor or progesterone receptor. Hypomethylation of P2 was associated with gain of HER2 and androgen receptor expression. These data suggest an association between miR-200b regulation and breast cancer subtype and a potential use of DNA methylation of miRNA promoters as a component of a suite of breast cancer biomarkers. Oncogene (2012) 31, 4182-4195; doi:10.1038/onc.2011.584; published online 9 January 201

    Microstructure and solidification sequence of the interdendritic region in a third generation single-crystal nickel-base superalloy

    No full text
    An analysis of the microstructure of the interdendritic regions in an as-cast third generation single-crystal nickel-base superalloy CMSX-10K has been carried out using automated serial sectioning with sequential focused ion beam (FIB) milling and image capture of the secondary electron image in a combined FIB–scanning electron microscope (SEM). Two interdendritic morphologies with vastly different γ/γ′ spacing were identified; these are (1) fine γ/γ′ morphology and (2) coarse cellular γ′ separated by narrow γ channels. The FIB results indicate that following primary solidification (L → γ), solidification of the interdendritic region commences in areas that show the fine γ/γ′ morphology, (1) on the γ dendrite lobe. This is followed by a gradual transition to growth of the coarse cellular γ/γ′ channel structure, (2) which occur up to the termination of the solidification process
    • …
    corecore