Endocrine therapy in epithelial ovarian cancer

INTRODUCTION: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer

Single nucleotide polymorphisms unravel hierarchical divergence and signatures of selection among Alaskan sockeye salmon (Oncorhynchus nerka) populations

<p>Abstract</p> <p>Background</p> <p>Disentangling the roles of geography and ecology driving population divergence and distinguishing adaptive from neutral evolution at the molecular level have been common goals among evolutionary and conservation biologists. Using single nucleotide polymorphism (SNP) multilocus genotypes for 31 sockeye salmon (<it>Oncorhynchus nerka</it>) populations from the Kvichak River, Alaska, we assessed the relative roles of geography (discrete boundaries or continuous distance) and ecology (spawning habitat and timing) driving genetic divergence in this species at varying spatial scales within the drainage. We also evaluated two outlier detection methods to characterize candidate SNPs responding to environmental selection, emphasizing which mechanism(s) may maintain the genetic variation of outlier loci.</p> <p>Results</p> <p>For the entire drainage, Mantel tests suggested a greater role of geographic distance on population divergence than differences in spawn timing when each variable was correlated with pairwise genetic distances. Clustering and hierarchical analyses of molecular variance indicated that the largest genetic differentiation occurred between populations from distinct lakes or subdrainages. Within one population-rich lake, however, Mantel tests suggested a greater role of spawn timing than geographic distance on population divergence when each variable was correlated with pairwise genetic distances. Variable spawn timing among populations was linked to specific spawning habitats as revealed by principal coordinate analyses. We additionally identified two outlier SNPs located in the major histocompatibility complex (MHC) class II that appeared robust to violations of demographic assumptions from an initial pool of eight candidates for selection.</p> <p>Conclusions</p> <p>First, our results suggest that geography and ecology have influenced genetic divergence between Alaskan sockeye salmon populations in a hierarchical manner depending on the spatial scale. Second, we found consistent evidence for diversifying selection in two loci located in the MHC class II by means of outlier detection methods; yet, alternative scenarios for the evolution of these loci were also evaluated. Both conclusions argue that historical contingency and contemporary adaptation have likely driven differentiation between Kvichak River sockeye salmon populations, as revealed by a suite of SNPs. Our findings highlight the need for conservation of complex population structure, because it provides resilience in the face of environmental change, both natural and anthropogenic.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Clinical Practice Guideline

Purpose: To provide resource-stratified, evidence-based recommendations on the secondary prevention of cervical cancer globally. Methods: ASCO convened a multidisciplinary, multinational panel of oncology, primary care, epidemiology, health economic, cancer control, public health, and patient advocacy experts to produce recommendations reflecting four resource-tiered settings. A review of existing guidelines, a formal consensus-based process, and a modified ADAPTE process to adapt existing guidelines were conducted. Other experts participated in formal consensus. Results: Seven existing guidelines were identified and reviewed, and adapted recommendations form the evidence base. Four systematic reviews plus cost-effectiveness analyses provided indirect evidence to inform consensus, which resulted in ≥ 75% agreement. Recommendations: Human papillomavirus (HPV) DNA testing is recommended in all resource settings; visual inspection with acetic acid may be used in basic settings. Recommended age ranges and frequencies by setting are as follows: maximal: ages 25 to 65, every 5 years; enhanced: ages 30 to 65, if two consecutive negative tests at 5-year intervals, then every 10 years; limited: ages 30 to 49, every 10 years; and basic: ages 30 to 49, one to three times per lifetime. For basic settings, visual assessment is recommended as triage; in other settings, genotyping and/or cytology are recommended. For basic settings, treatment is recommended if abnormal triage results are present; in other settings, colposcopy is recommended for abnormal triage results. For basic settings, treatment options are cryotherapy or loop electrosurgical excision procedure; for other settings, loop electrosurgical excision procedure (or ablation) is recommended. Twelve-month post-treatment follow-up is recommended in all settings. Women who are HIV positive should be screened with HPV testing after diagnosis and screened twice as many times per lifetime as the general population. Screening is recommended at 6 weeks postpartum in basic settings; in other settings, screening is recommended at 6 months. In basic settings without mass screening, infrastructure for HPV testing, diagnosis, and treatment should be developed.Additional information can be found at www.asco.org/rs-cervical-cancer-secondary-prev-guideline and www.asco.org/guidelineswiki.It is the view of of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement, but not replace, local guidelines

ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

<p>Abstract</p> <p>Background</p> <p>One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer susceptibility gene 1). To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity.</p> <p>Methods</p> <p>Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC), gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay.</p> <p>Results</p> <p>ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001). In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002) while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032). A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45).</p> <p>Conclusion</p> <p>Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with <it>in vitro </it>chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered.</p

Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

ACKNOWLEDGMENTS This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003).Peer reviewedPublisher PD

Wired for Her Face? Male Attentional Bias for Female Faces

Under conditions of inattention or deficits in orienting attention, special classes of stimuli (e.g. faces, bodies) are more likely to be perceived than other stimuli. This suggests that biologically salient visual stimuli automatically recruit attention, even when they are task-irrelevant or ignored. Here we report results from a behavioral experiment with female and male subjects and two magnetoencephalography (MEG) experiments with male subjects only, in which we investigated attentional capture with face and hand stimuli. In both the behavioral and MEG experiments, subjects were required to count the number of gender-specific targets from either face or hand categories within a block of stimuli. In the behavioral experiment, we found that male subjects were significantly more accurate in response to female than male face target blocks. There was no corresponding effect found in response to hand target blocks. Female subjects did not show a gender-based difference in response to face or hand target blocks. MEG results indicated that the male subjects’ responses to face stimuli in primary visual cortex (V1) and the face-selective part of the fusiform gyrus (FG) were reduced when male face stimuli were not relevant to the task, whereas female faces maintained a strong response in these areas in both task-relevant and task-irrelevant conditions. These results suggest that within the male brain, female face stimuli are more resilient to suppression than male faces, once attention is drawn to the part of the visual field where the face appears

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let