A paradigm for the treatment of prostate cancer bone metastases based on an understanding of tumor cell–microenvironment interactions

The pliability of cancer cells to mutate into several different phenotypes in an attempt to find one that will survive and colonize at the metastatic site is a tremendous “hurdle” to overcome in designing novel cancer therapeutics. New targets of therapy are essential if we are to effectively overcome the evasiveness of cancer. The interaction between the tumor cell and the surrounding microenvironment creates a vicious cycle that perpetuates disease survival and progression. The future of cancer therapy resides in the ability to focus on the recruited and exploited relationships of the cancer cell with the host environment. These therapies target cancer cell growth early and interrupt the vicious cycle that is created by the tumor cells interacting with bone components by inhibiting osteoclasts, osteoblasts, stromal cells, and endothelial cells. They alter the bone microenvironment, creating a hostile “soil” that prevents the “seed” from developing into bone metastases and represent a potential new platform for the development of prostate cancer therapeutics. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48763/1/20522_ftp.pd

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Growth of Long Range Forward-Backward Multiplicity Correlations with Centrality in Au+Au Collisions at sNN\sqrt{s_{NN}} = 200 GeV

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au+Au and $\textit{p+p}$ collisions at $\sqrt{s_{NN}}$ = 200 GeV. Strong short and long range correlations (LRC) are seen in central Au+Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short range correlations are observed in peripheral Au+Au collisions. Both the Dual Parton Model (DPM) and the Color Glass Condensate (CGC) predict the existence of the long range correlations. In the DPM the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC longitudinal color flux tubes generate the LRC. The data is in qualitative agreement with the predictions from the DPM and indicates the presence of multiple parton interactions.Comment: 6 pages, 3 figures The abstract has been slightly modifie

K/pi Fluctuations at Relativistic Energies

We report results for $K/\pi$ fluctuations from Au+Au collisions at $\sqrt{s_{NN}}$ = 19.6, 62.4, 130, and 200 GeV using the STAR detector at the Relativistic Heavy Ion Collider. Our results for $K/\pi$ fluctuations in central collisions show little dependence on the incident energies studied and are on the same order as results observed by NA49 at the Super Proton Synchrotron in central Pb+Pb collisions at $\sqrt{s_{NN}}$ = 12.3 and 17.3 GeV. We also report results for the collision centrality dependence of $K/\pi$ fluctuations as well as results for $K^{+}/\pi^{+}$, $K^{-}/\pi^{-}$, $K^{+}/\pi^{-}$, and $K^{-}/\pi^{+}$ fluctuations. We observe that the $K/\pi$ fluctuations scale with the multiplicity density, $dN/d\eta$, rather than the number of participating nucleons.Comment: 6 pages, 4 figure

Forward Neutral Pion Transverse Single Spin Asymmetries in p+p Collisions at \sqrt{s}=200 GeV

We report precision measurements of the Feynman-x dependence, and first measurements of the transverse momentum dependence, of transverse single spin asymmetries for the production of \pi^0 mesons from polarized proton collisions at \sqrt{s}=200 GeV. The x_F dependence of the results is in fair agreement with perturbative QCD model calculations that identify orbital motion of quarks and gluons within the proton as the origin of the spin effects. Results for the p_T dependence at fixed x_F are not consistent with pQCD-based calculations.Comment: 6 pages, 4 figure

Fatigue in low-grade glioma

Contains fulltext : 80675.pdf (publisher's version ) (Closed access)The aim of this study was to determine the prevalence and severity of fatigue in long-term survivors with a low-grade glioma (LGG), and to analyze the relationship between fatigue and demographic variables, disease duration, tumor characteristics, former tumor treatment modalities, antiepileptic drug (AED) use, self-reported concentration, motivation, and activity. Fifty-four patients with stable disease (age range, 25-73 years) who were diagnosed and treated more than 8 years ago were included in this study. Fatigue was analyzed with the Checklist Individual Strength (CIS). Thirty-nine percent of the LGG patients were severely fatigued, with older patients being most affected. Severe fatigue was associated with AED use, and with reduced self-reported concentration, motivation, and activity. No relation was found between fatigue and gender, histology, tumor laterality, disease duration, type of neurosurgical intervention and radiation treatment. Fatigue is a severe problem in a large proportion of long-term surviving LGG patients

Leaf litter decomposition in temperate deciduous forest stands with a decreasing fraction of beech (Fagus sylvatica)

We hypothesised that the decomposition rates of leaf litter will increase along a gradient of decreasing fraction of the European beech (Fagus sylvatica) and increasing tree species diversity in the generally beech-dominated Central European temperate deciduous forests due to an increase in litter quality. We studied the decomposition of leaf litter including its lignin fraction in monospecific (pure beech) stands and in stands with up to five tree genera (Acer spp., Carpinus betulus, Fagus sylvatica, Fraxinus excelsior, Tilia spp.) using a litterbag approach. Litter and lignin decomposition was more rapid in stand-representative litter from multispecific stands than in litter from pure beech stands. Except for beech litter, the decomposition rates of species-specific tree litter did not differ significantly among the stand types, but were most rapid in Fraxinus excelsior and slowest in beech in an interspecific comparison. Pairwise comparisons of the decomposition of beech litter with litter of the other tree species (except for Acerplatanoides) revealed a “home field advantage” of up to 20% (more rapid litter decomposition in stands with a high fraction of its own species than in stands with a different tree species composition). Decomposition of stand-representative litter mixtures displayed additive characteristics, not significantly more rapid than predicted by the decomposition of litter from the individual tree species. Leaf litter decomposition rates were positively correlated with the initial N and Ca concentrations of the litter, and negatively with the initial C:N, C:P and lignin:N ratios. The results support our hypothesis that the overall decomposition rates are mainly influenced by the chemical composition of the individual litter species. Thus, the fraction of individual tree species in the species composition seems to be more important for the litter decomposition rates than tree species diversity itself

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p <1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.Peer reviewe