45 research outputs found
Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study
Prognostic factors for disease-free survival in patients treated before 2005 September: multivariate analysis. (DOCX 15Â kb
Participants' uptake of clinical trial results: a randomised experiment
BJC OPENInternational audienceBACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results
A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers
HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism
Genome profiling of ERBB2-amplified breast cancers
<p>Abstract</p> <p>Background</p> <p>Around 20% of breast cancers (BC) show <it>ERBB2 </it>gene amplification and overexpression of the ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs, genomically and biologically heterogeneous, may help understand their behavior and design new therapeutic strategies.</p> <p>Methods</p> <p>We defined the high resolution genome and gene expression profiles of 54 <it>ERBB2</it>-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. Expression of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was assessed by immunohistochemistry to evaluate the functional ERBB2 status and identify co-expressions.</p> <p>Results</p> <p>First, we identified the <it>ERBB2</it>-<it>C17orf37</it>-<it>GRB7 </it>genomic segment as the minimal common 17q12-q21 amplicon, and <it>CRKRS </it>and <it>IKZF3 </it>as the most frequent centromeric and telomeric amplicon borders, respectively. Second, GISTIC analysis identified 17 other genome regions affected by copy number aberration (CNA) (amplifications, gains, losses). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in <it>ERBB2</it>-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) <it>ERBB2</it>-amplified BCs were different. The WNT/β-catenin signaling pathway was involved in ER- <it>ERBB2</it>-amplified BCs, and <it>PVT1 </it>and <it>TRPS1 </it>were candidate oncogenes associated with ER+ <it>ERBB2</it>-amplified BCs. The size of the <it>ERBB2 </it>amplicon was different in inflammatory (IBC) and non-inflammatory BCs. <it>ERBB2</it>-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. IHC results showed (i) a linear relationship between <it>ERBB2 </it>gene amplification and its gene and protein expressions with a good correlation between ERBB2 expression and phosphorylation status; (ii) a potential signaling cross-talk between EGFR or IGF1R and ERBB2, which could influence response of <it>ERBB2</it>-positive BCs to inhibitors. FOXA1 was frequently coexpressed with ERBB2 but its expression did not impact on the outcome of patients with <it>ERBB2</it>-amplified tumors.</p> <p>Conclusion</p> <p>We have shown that ER+ and ER- <it>ERBB2</it>-amplified BCs are different, distinguished <it>ERBB2 </it>amplicons in IBC and non-IBC, and identified genomic features that may be useful in the design of alternative therapeutical strategies.</p
The nonperturbative functional renormalization group and its applications
The renormalization group plays an essential role in many areas of physics,
both conceptually and as a practical tool to determine the long-distance
low-energy properties of many systems on the one hand and on the other hand
search for viable ultraviolet completions in fundamental physics. It provides
us with a natural framework to study theoretical models where degrees of
freedom are correlated over long distances and that may exhibit very distinct
behavior on different energy scales. The nonperturbative functional
renormalization-group (FRG) approach is a modern implementation of Wilson's RG,
which allows one to set up nonperturbative approximation schemes that go beyond
the standard perturbative RG approaches. The FRG is based on an exact
functional flow equation of a coarse-grained effective action (or Gibbs free
energy in the language of statistical mechanics). We review the main
approximation schemes that are commonly used to solve this flow equation and
discuss applications in equilibrium and out-of-equilibrium statistical physics,
quantum many-particle systems, high-energy physics and quantum gravity.Comment: v2) Review article, 93 pages + bibliography, 35 figure
Nonperturbative renormalization group for the diffusive epidemic process
We consider the Diffusive Epidemic Process (DEP), a two-species
reaction-diffusion process originally proposed to model disease spread within a
population. This model exhibits a phase transition from an active epidemic to
an absorbing state without sick individuals. Field-theoretic analyses suggest
that this transition belongs to the universality class of Directed Percolation
with a Conserved quantity (DP-C). However, some exact predictions derived from
the symmetries of DP-C seem to be in contradiction with lattice simulations.
Here we revisit the field theory of both DP-C and DEP. We discuss in detail the
symmetries present in the various formulations of both models, some of which
had not been identified previously. We then investigate the DP-C model using
the derivative expansion of the non-perturbative renormalization group
formalism. We recover previous results for DP-C near its upper critical
dimension , but show how the corresponding fixed point seems to no
longer exist below . Consequences for the DEP universality class
are considered.Comment: 12 pages, 2 figures, some correction
Effects of termite sheetings on soil properties under two contrasting soil management practices
Soil organic matter (SOM) dynamics and termite activity have now been widely accepted as key players for improving soil properties in tropical agro-ecosystems. Numerous studies have described environmental impacts of aboveground termite mounds, while few data are available on temporary structures built for food foraging, called termite sheetings. The effects of termite activity on soil properties resulting from organic matter (OM) amendment under two contrasting management practices were studied in similar pedological and climatic conditions in Southern India (Auroville). Our results showed an increase in bio-available nutrients (K, Mg and P), organic carbon (OC) content, cationic exchange capacity (CEC), exchangeable base cations and water pH in the termite sheetings compared to the underlying and reference soils, in the organic tilled field. On the other hand, only bio-available K increased in the permanent raised beds. Aggregation processes were improved in termite sheetings for the organic tilled field, as the amounts of macroaggregates (250 mu m-2 mm) and protected microaggregates increased, whereas the amount of free microaggregates (50-250 mu m) decreased. Moreover, termite activity favoured SOM storage in termite sheetings by increasing OC content in each aggregate fraction, while no differences were observed in the permanent raised beds. Our study demonstrates that termite activity can improve nutrient availability, carbon storage and pH conditions in agro-ecosystems but that the magnitude of the effect likely depends on the agronomic practices in use