1,490 research outputs found
Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial
Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients
Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial
Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients
Role of domain walls in the abnormal photovoltaic effect in BiFeO3
Recently, the anomalous photovoltaic (PV) effect in BiFeO3 (BFO) thin
films, which resulted in open circuit voltages (V-oc) considerably
larger than the band gap of the material, has generated a revival of the
entire field of photoferroelectrics. Here, via temperature-dependent PV
studies, we prove that the bulk photovoltaic (BPV) effect, which has
been studied in the past for many non-centrosymmetric materials, is at
the origin of the anomalous PV effect in BFO films. Moreover, we show
that irrespective of the measurement geometry, V-oc as high as 50V can
be achieved by controlling the conductivity of domain walls (DW). We
also show that photoconductivity of the DW is markedly higher than in
the bulk of BFO
Recognition and Accommodation at the Androgen Receptor Coactivator Binding Interface
Prostate cancer is a leading killer of men in the industrialized world. Underlying this disease is the aberrant action of the androgen receptor (AR). AR is distinguished from other nuclear receptors in that after hormone binding, it preferentially responds to a specialized set of coactivators bearing aromatic-rich motifs, while responding poorly to coactivators bearing the leucine-rich “NR box” motifs favored by other nuclear receptors. Under normal conditions, interactions with these AR-specific coactivators through aromatic-rich motifs underlie targeted gene transcription. However, during prostate cancer, abnormal association with such coactivators, as well as with coactivators containing canonical leucine-rich motifs, promotes disease progression. To understand the paradox of this unusual selectivity, we have derived a complete set of peptide motifs that interact with AR using phage display. Binding affinities were measured for a selected set of these peptides and their interactions with AR determined by X-ray crystallography. Structures of AR in complex with FxxLF, LxxLL, FxxLW, WxxLF, WxxVW, FxxFF, and FxxYF motifs reveal a changing surface of the AR coactivator binding interface that permits accommodation of both AR-specific aromatic-rich motifs and canonical leucine-rich motifs. Induced fit provides perfect mating of the motifs representing the known family of AR coactivators and suggests a framework for the design of AR coactivator antagonists
Reprocessing the Hipparcos data for evolved stars III Revised Hipparcos period-luminosity relationship for galactic long-period variable stars
We analyze the K band luminosities of a sample of galactic long-period
variables using parallaxes measured by the Hipparcos mission. The parallaxes
are in most cases re-computed from the Hipparcos Intermediate Astrometric Data
using improved astrometric fits and chromaticity corrections. The K band
magnitudes are taken from the literature and from measurements by COBE, and are
corrected for interstellar and circumstellar extinction. The sample contains
stars of several spectral types: M, S and C, and of several variability
classes: Mira, semiregular SRa, and SRb. We find that the distribution of stars
in the period-luminosity plane is independent of circumstellar chemistry, but
that the different variability types have different P-L distributions. Both the
Mira variables and the SRb variables have reasonably well-defined
period-luminosity relationships, but with very different slopes. The SRa
variables are distributed between the two classes, suggesting that they are a
mixture of Miras and SRb, rather than a separate class of stars. New
period-luminosity relationships are derived based on our revised Hipparcos
parallaxes. The Miras show a similar period-luminosity relationship to that
found for Large Magellanic Cloud Miras by Feast et al. (1989). The maximum
absolute K magnitude of the sample is about -8.2 for both Miras and
semi-regular stars, only a little fainter than the expected AGB limit. We show
that the stars with the longest periods (P>400d) have high mass loss rates and
are almost all Mira variables.Comment: Comments welcome. Submitted to A&A 11 pages, 7 figs, 3 table
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