Tissue invasion and metastasis: Molecular, biological and clinical perspectives

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays

Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of prime importance in probing new physics. Here 7421 +/- 105 signal events from the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A time-dependent fit to the data yields a value of phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201

First observation of the decay Bˉs0→D0K∗0\bar{B}^0_s \to D^0 K^{*0} and a measurement of the ratio of branching fractions B(Bˉs0→D0K∗0)B(Bˉ0→D0ρ0)\frac{{\cal B}(\bar{B}^0_s \to D^0 K^{*0})}{{\cal B}(\bar{B}^0 \to D^0 \rho^0)}

The first observation of the decay $\bar{B}^0_s \to D^0 K^{*0}$ using $pp$ data collected by the LHCb detector at a centre-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 36 pb$^{-1}$, is reported. A signal of $34.4 \pm 6.8$ events is obtained and the absence of signal is rejected with a statistical significance of more than nine standard deviations. The $\bar{B}^0_s \to D^0 K^{*0}$ branching fraction is measured relative to that of $\bar{B}^0 \to D^0 \rho^0$: $\frac{{\cal B}(\bar{B}^0_s \to D^0 K^{*0})}{{\cal B}(\bar{B}^0 \to D^0 \rho^0)} = 1.48 \pm 0.34 \pm 0.15 \pm 0.12$, where the first uncertainty is statistical, the second systematic and the third is due to the uncertainty on the ratio of the $B^0$ and $B^0_s$ hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269

Observation of CP violation in B+ to DK+ decays

An analysis of B+ to DK+ and B+ to Dpi+ decays is presented where the D meson is reconstructed in the two-body final states: K+pi-, K+K-, pi+pi- and pi+K-. Using 1.0 fb-1 of LHCb data, measurements of several observables are made including the first observation of the suppressed mode B+ to DK+, D to pi+K-. CP violation in B+ to DK+ decays is observed with 5.8 sigma significance

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Measurement of the Ds+ - Ds- production asymmetry in 7 TeV pp collisions

Heavy quark production in 7 TeV centre-of-mass energy pp collisions at the LHC is not necessarily flavour symmetric. The production asymmetry, A_P, between Ds+ and Ds- mesons is studied using the \phi\pi(+/-) decay mode in a data sample of 1.0/fb collected with the LHCb detector. The difference between \pi+ and \pi- detection efficiencies is determined using the ratios of fully reconstructed to partially reconstructed D*(+/-) decays. The overall production asymmetry in the Ds rapidity region 2.0 to 4.5 with transverse momentum larger than 2 GeV is measured to be A_P=(-0.33 +/- 0.22 +/- 0.10)%. This result can constrain models of heavy flavour production.Comment: 13 pages, 10 figures, updated to published versio

Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Gaseous Reduction of Copper

Confidentia