264 research outputs found
Conflicting Views on Chemical Carcinogenesis Arising from the Design and Evaluation of Rodent Carcinogenicity Studies
Conflicting views have been expressed frequently on assessments of human cancer risk of environmental agents based on animal carcinogenicity data; this is primarily because of uncertainties associated with extrapolations of toxicologic findings from studies in experimental animals to human circumstances. Underlying these uncertainties are issues related to how experiments are designed, how rigorously hypotheses are tested, and to what extent assertions extend beyond actual findings. National and international health agencies regard carcinogenicity findings in well-conducted experimental animal studies as evidence of potential carcinogenic risk to humans. Controversies arise when both positive and negative carcinogenicity data exist for a specific agent or when incomplete mechanistic data suggest a possible species difference in response. Issues of experimental design and evaluation that might contribute to disparate results are addressed in this article. To serve as reliable sources of data for the evaluation of the carcinogenic potential of environmental agents, experimental studies must include a) animal models that are sensitive to the end points under investigation; b) detailed characterization of the agent and the administered doses; c) challenging doses and durations of exposure (at least 2 years for rats and mice); d) sufficient numbers of animals per dose group to be capable of detecting a true effect; e) multiple dose groups to allow characterization of dose–response relationships, f) complete and peer-reviewed histopathologic evaluations; and g) pairwise comparisons and analyses of trends based on survival-adjusted tumor incidence. Pharmacokinetic models and mechanistic hypotheses may provide insights into the biological behavior of the agent; however, they must be adequately tested before being used to evaluate human cancer risk
Mutational analysis of Polycomb genes in solid tumours identifies <i>PHC3</i> amplification as a possible cancer-driving genetic alteration.
Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours.
Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs.
Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration.
Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours
Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser
Gisbert Winnewisser's astronomical career was practically coextensive with
the whole development of molecular radio astronomy. Here I would like to pick
out a few of his many contributions, which I, personally, find particularly
interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter
Astronomy Group. To appear in the Proceedings of the 4th
Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies"
eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer:
Berlin
Molecular classification improves risk assessment in adult BCR-ABL1–negative B-ALL
Genomic classification has improved risk assignment of pediatric but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (NCT00002514) trial accrued 1229 BCR-ABL1-negative adolescent/adult B-ALL patients (aged 14-65 years). While 93% of patients achieved remission, 41% relapsed at a median of 13 months (range 28 days to 12 years). Five-year overall survival (5yr-OS) was 42% (95% CI, 39, 44). Transcriptome sequencing (n=238), gene expression profiling (n=210), cytogenetics (n=197) and fusion PCR (n=274) enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients in the outcome analysis, 29.5% of cases had favorable outcomes with 5yr-OS of 65-80% and were deemed standard-risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5yr-OS of 0-27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); and 20.3% had intermediate-risk genotypes with 5yr-OS of 33-45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like and TP53 mutations occurred in low-hypodiploid (54%) and BCL2/MYC-rearranged patients (33%), but were not independently associated with outcome. Of patients considered high-risk for relapse based on presenting age and WBC count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non-risk-adapted approach on a single trial show the prognostic importance of genomic analyses which may translate into future therapeutic benefits
Azimuthal anisotropy and correlations at large transverse momenta in and Au+Au collisions at = 200 GeV
Results on high transverse momentum charged particle emission with respect to
the reaction plane are presented for Au+Au collisions at =
200 GeV. Two- and four-particle correlations results are presented as well as a
comparison of azimuthal correlations in Au+Au collisions to those in at
the same energy. Elliptic anisotropy, , is found to reach its maximum at
GeV/c, then decrease slowly and remain significant up to
-- 10 GeV/c. Stronger suppression is found in the back-to-back
high- particle correlations for particles emitted out-of-plane compared to
those emitted in-plane. The centrality dependence of at intermediate
is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004
Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV
The results from the STAR Collaboration on directed flow (v_1), elliptic flow
(v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution
of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and
compared with results from other experiments and theoretical models. Results
for identified particles are presented and fit with a Blast Wave model.
Different anisotropic flow analysis methods are compared and nonflow effects
are extracted from the data. For v_2, scaling with the number of constituent
quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and
quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures
modified, but data the same. However, in Fig. 35 the hydro calculations are
corrected in this version. The data tables are available at
http://www.star.bnl.gov/central/publications/ by searching for "flow" and
then this pape
Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV
We report on the rapidity and centrality dependence of proton and anti-proton
transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as
measured by the STAR experiment at RHIC. Our results are from the rapidity and
transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons
and anti-protons, transverse mass distributions become more convex from
peripheral to central collisions demonstrating characteristics of collective
expansion. The measured rapidity distributions and the mean transverse momenta
versus rapidity are flat within |y|<0.5. Comparisons of our data with results
from model calculations indicate that in order to obtain a consistent picture
of the proton(anti-proton) yields and transverse mass distributions the
possibility of pre-hadronic collective expansion may have to be taken into
account.Comment: 4 pages, 3 figures, 1 table, submitted to PR
- …