Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010

PURPOSE: Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, have been shown in randomized clinical trials to reduce the risk of developing primary invasive breast cancer (IBC) in high-risk women. In 1998, the U.S. Food and Drug Administration (FDA) used these studies as a basis for approving tamoxifen for primary breast chemoprevention in both premenopausal and postmenopausal women at high risk. In 2007, the FDA approved raloxifene for primary breast cancer chemoprevention for postmenopausal women. METHODS: Data from the year 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of tamoxifen and raloxifene use for chemoprevention of primary breast cancers among U.S. women. RESULTS: Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95% CI, 518–114,864) for U.S. women aged 35 to 79 for tamoxifen. Prevalence was 96,890 (95% CI, 41,277–192,391) for U.S. women aged 50 to79 for raloxifene. CONCLUSION: Use of tamoxifen and raloxifene for prevention of primary breast cancers continues to be low. In 2010, women reporting medication use for breast cancer chemoprevention were primarily using the more recently FDA-approved drug raloxifene. Multiple possible explanations for the low use exist, including lack of awareness and/or concern about side effects among primary care physicians and patients

Bland tjänstemän och eldsjälar

Bland tjänstemän och eldsjälar Innehållsförteckning – Inledaren: Lyckan att vara skäribo av Pia Prost – Sjömanshusen av Kasper Westerlund – En kronolänsman i Nagu under ryska tiden av Birgitta Edelman-Holmberg – Stubben av Maria Sjöblom – Prosten Maximilian Lagerbohms bildskatt från Houtskär av Pia Prost – Vem är skärgårdens bästa bundsförvant av Jan Sundberg – En framtida skärgård – hur vill vi bo? av Nina Söderlund – Att krympa smart av Elina Auri & Christell Åström – Bergö vägvisare för nya servicelösningar i skärgården av Pia Prost – "Pelles Elmuseum" på Emsalö vidare inom familjen av Thure Malmberg – Husö biologiska station 60 år Ea Maria Blomqvist – Dagens forskning på Husö biologiska station av Pia Prost – Bron mellan Pargas och Nagu Pia Prost – Stalin på grund av Anders Moliis-Mellberg – Sibboroddare siktar på guld i Sulkava av Thure Malmberg – Skräntärnan speglar en skärgårdsnatur i förändring av Patrik Byholm Bokhörnan: – Ett bokprojekt ser dagens ljus av Håkan Eklund – Utförligt om det flytande kulturarvet av Kasper Westerlund – Skärinytt – Sista bilde

Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013-2014.

BACKGROUND: Sociodemographic inequalities in cancer treatment have been generally described, but there is little evidence regarding patients with advanced cancer. Understanding variation in the management of these patients may provide insights into likely mechanisms leading to inequalities in survival. METHODS: We identified 50,232 patients with stage IV lung, oesophageal, pancreatic and stomach cancer from the English national cancer registry. A generalised linear model with a Poisson error structure was used to explore variation in radiotherapy and chemotherapy within 6 months from diagnosis by age, sex, deprivation, ethnicity, cancer site, comorbidity and, additionally, performance status. RESULTS: There was substantial variation by cancer site, large gradients by age, and non-trivial associations with comorbidity and deprivation. After full adjustment, more deprived patients were consistently least likely to be treated with chemotherapy alone or chemotherapy and radiotherapy combined compared with less deprived patients with equally advanced disease stage (treatment rate ratio: 0.82 95% CI (0.78, 0.87) for CT, 0.78 95% CI (0.71, 0.85) for CTRT p < 0.0001). CONCLUSIONS: There was marked variation in the management of patients with stage IV cancer. Routinely collected data could be used for surveillance across all cancers to help reduce treatment variation and optimise outcomes among patients with advanced cancer

QTL for phytosterol and sinapate ester content in Brassica napus L. collocate with the two erucic acid genes

Improving oil and protein quality for food and feed purposes is an important goal in rapeseed (Brassica napus L.) breeding programs. Rapeseed contains phytosterols, used to enrich food products, and sinapate esters, which are limiting the utilization of rapeseed proteins in the feed industry. Increasing the phytosterol content of oil and lowering sinapate ester content of meal could increase the value of the oilseed rape crop. The objective of the present study was to identify quantitative trait loci (QTL) for phytosterol and sinapate ester content in a winter rapeseed population of 148 doubled haploid lines, previously found to have a large variation for these two traits. This population also segregated for the two erucic acid genes. A close negative correlation was found between erucic acid and phytosterol content (Spearman’s rank correlation, rs = −0.80**). For total phytosterol content, three QTL were detected, explaining 60% of the genetic variance. The two QTL with the strongest additive effects were mapped on linkage groups N8 and N13 within the confidence intervals of the two erucic acid genes. For sinapate ester content four QTL were detected, explaining 53% of the genetic variance. Again, a close negative correlation was found between erucic acid and sinapate ester content (rs = −0.66**) and the QTL with the strongest additive effects mapped on linkage groups N8 and N13 within the confidence intervals of the two erucic acid genes. The results suggests, that there is a pleiotropic effect of the two erucic acid genes on phytosterol and sinapate ester content; the effect of the alleles for low erucic acid content is to increase phytosterol and sinapate ester content. Possible reasons for this are discussed based on known biosynthetic pathways

Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up

Background: Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. Methods: ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. Results: In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (&lt;= 80 mu g/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. Conclusions: S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue

Long-term symptoms in dizzy patients examined in a university clinic

Background: The long-term course of dizziness was investigated combining medical chart and survey data. The survey was undertaken median (interquartile range (IQR)) 4.6 (4.3) years after the initial medical examination. Methods: Chart data comprised sex, age, diagnosis, symptom duration, postural sway and neck pain. Survey data comprised symptom severity assessed by the Vertigo Symptom Scale – Short Form (VSS-SF), and data regarding current state of dizziness, medication, neck pain and other chronic conditions. Results: The sample consisted of 503 patients, the mean (standard deviation (SD)) age was 50.0 (11.6) years, women being slightly overrepresented (60%). Severe problems with dizziness (VSS-SF mean (SD) 13.9, (10.8)) were indicated in the total group and in 5 of 6 diagnostic sub-groups. Vertigo/balance- and autonomic/anxiety-related symptoms were present in all groups. Current dizziness was confirmed by 73% who had significantly more severe problems than the non-dizzy (VSS-SF mean (SD): 17.2 (10.1) versus 5.0 (7.3)). Symptoms were related to vertigo/balance more than to autonomic/anxiety (test of interaction p < 0.001). Based on simple logistic regression analysis, sex, symptom duration, neck pain, sway and diagnoses predicted dizziness. Symptom duration and neck pain remained predictors in the adjusted analysis. Age, symptom duration, neck pain, sway and diagnoses predicted vertigo/balance-related dizziness in both regression analyses. Sex, neck pain and sway predicted development of autonomic/anxiety-related dizziness according to simple regression analysis, while only neck pain remained a significant predictor in the adjusted analysis. With respect to diagnosis, simple regression analysis showed significant reduced likelihood for development of dizziness in all vestibular sub-groups when compared to the non-otogenic dizziness group. With respect to vertigo/balance- and autonomic/anxiety-related symptoms, the implication of diagnostic belonging varied. No effect of diagnoses was seen in adjusted analyses. Conclusion: The majority of patients had persistent and severe problems with dizziness. The wait-and-see attitude before referral to specialist institutions may be questioned. Early, active movements seem necessary, and attention should be paid to the presence of neck pain. Diagnoses had limited prognostic value. Questionnaire-based evaluations could assist in classification and identification of type of dizziness and thereby provide a better basis for specific rehabilitation

Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652

Diabetes in Danish Bank Voles (M. glareolus): Survivorship, Influence on Weight, and Evaluation of Polydipsia as a Screening Tool for Hyperglycaemia

BACKGROUND: Previous studies have concluded that the development of polydipsia (PD, a daily water intake ≥ 21 ml) among captive Danish bank voles, is associated with the development of a type 1 diabetes (T1D), based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin. AIM AND METHODS: We retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent. RESULTS: We found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively. CONCLUSION: The relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods

The Caenorhabditis elegans Elongator Complex Regulates Neuronal α-tubulin Acetylation

Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore, a genetic screen was employed in the nematode Caenorhabditis elegans that identified the Elongator complex as a possible regulator of α-tubulin acetylation. Detailed characterization of mutant animals revealed that the acetyltransferase activity of the Elongator is indeed required for correct acetylation of microtubules and for neuronal development. Moreover, the velocity of vesicles on microtubules was affected by mutations in Elongator. Elongator mutants also displayed defects in neurotransmitter levels. Furthermore, acetylation of α-tubulin was shown to act as a novel signal for the fine-tuning of microtubules dynamics by modulating α-tubulin turnover, which in turn affected neuronal shape. Given that mutations in the acetyltransferase subunit of the Elongator (Elp3) and in a scaffold subunit (Elp1) have previously been linked to human neurodegenerative diseases, namely Amyotrophic Lateral Sclerosis and Familial Dysautonomia respectively highlights the importance of this work and offers new insights to understand their etiology