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3.
Pharmacogenomics J ; 10(3): 191-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20038957

ABSTRACT

The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide.


Subject(s)
PPAR delta/genetics , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Sulfotransferases/genetics , Taxoids/therapeutic use , Thalidomide/therapeutic use , Adult , Aged , Docetaxel , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis/methods , Orchiectomy , Pharmacogenetics , Polymorphism, Single Nucleotide , Taxoids/adverse effects , Taxoids/pharmacokinetics , Thalidomide/adverse effects , Thalidomide/pharmacokinetics , Carbohydrate Sulfotransferases
5.
Phys Rev Lett ; 97(15): 152301, 2006 Oct 13.
Article in English | MEDLINE | ID: mdl-17155321

ABSTRACT

Transverse momentum spectra of pi+/-, p, and p up to 12 GeV/c at midrapidity in centrality selected Au + Au collisions at square root sNN=200 GeV are presented. In central Au + Au collisions, both pi +/- and p(p) show significant suppression with respect to binary scaling at pT approximately >4 GeV/c. Protons and antiprotons are less suppressed than pi+/-, in the range 1.5 approximately < pT approximately < 6 GeV/c. The pi-/pi+ and p/p ratios show at most a weak pT dependence and no significant centrality dependence. The p/pi ratios in central Au + Au collisions approach the values in p + p and d + Au collisions at pT approximately >5 GeV/c. The results at high pT indicate that the partonic sources of pi+/-, p, and p have similar energy loss when traversing the nuclear medium.

6.
Calcif Tissue Int ; 77(1): 23-9, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16007484

ABSTRACT

The amelogenin proteins regulate enamel mineral formation in the developing tooth. The human AMELX gene, which encodes the amelogenin proteins, is located within an intron of the Arhgap 6 gene. ARHGAP 6 encodes a Rho GAP, which regulates activity of Rho A, a small G protein involved in intracellular signal transduction. Mice were generated in which the entire ARHGAP 6 gene was deleted by Cre-mediated recombination, which also removed the nested Amel X gene. Enamel from these mice appeared chalky white, and the molars showed excessive wear. The enamel layer was hypoplastic and non-prismatic, whereas other dental tissues had normal morphology. This phenotype is similar to that reported for Amel X null mice, which have a short deletion that removed the region surrounding the translation initiation site, and resembles some forms of X-linked amelogenesis imperfecta in humans. Analysis of the enamel from the Arhgap 6/Amel X-deleted mice verifies that the Amel X gene is nested within the murine Arhgap 6 gene and shows that removal of the entire Amel X gene leads to a phenotype similar to the earlier Amel X null mouse results, in which no amelogenin protein was detected. However, an unusual layer of aprismatic enamel covers the enamel surface, which may be related to the 1.1-Mb deletion, which included Arhgap 6 in these mice.


Subject(s)
Dental Enamel Proteins/genetics , Dental Enamel/pathology , GTPase-Activating Proteins/genetics , Gene Deletion , Mice, Transgenic/genetics , Amelogenesis Imperfecta/genetics , Amelogenin , Animals , Disease Models, Animal , Female , Humans , Male , Mice , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Tooth/metabolism , Tooth/ultrastructure
7.
Phys Rev Lett ; 94(6): 062301, 2005 Feb 18.
Article in English | MEDLINE | ID: mdl-15783724

ABSTRACT

Midrapidity open charm spectra from direct reconstruction of D0(D0)-->K-/+pi+/- in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at squareroot[sNN]=200 GeV are reported. The D0(D0) spectrum covers a transverse momentum (pT) range of 0.1

8.
Phys Rev Lett ; 95(15): 152301, 2005 Oct 07.
Article in English | MEDLINE | ID: mdl-16241721

ABSTRACT

Charged hadrons in [EQUATION: SEE TEXT] associated with particles of [EQUATION: SEE TEXT] are reconstructed in pp and Au+Au collisions at sqrt[sNN]=200 GeV. The associated multiplicity and p magnitude sum are found to increase from pp to central Au+Au collisions. The associated p distributions, while similar in shape on the nearside, are significantly softened on the awayside in central Au+Au relative to pp and not much harder than that of inclusive hadrons. The results, consistent with jet quenching, suggest that the awayside fragments approach equilibration with the medium traversed.

9.
Genomics ; 51(2): 251-61, 1998 Jul 15.
Article in English | MEDLINE | ID: mdl-9722948

ABSTRACT

Microphthalmia with linear skin defects (MLS) is an X-linked dominant male-lethal syndrome caused by different deletions of chromosome Xp22. Through the screening of cDNA libraries with the cross-species conserved marker 61B3-R (DXS1141), we identified a new gene at the telomeric breakpoint of the MLS critical region, which encodes a transcript containing a RING finger domain. This novel gene was independently cloned by another group and found to be mutated in Opitz syndrome. In this study we characterized the expression pattern of this gene, identified various splice variants, delineated its exon-intron boundaries, and determined that it is not mutated in either Aicardi or Goltz syndrome, two X-linked dominant conditions with phenotypes that overlap with that of MLS syndrome. This novel RING finger gene is expressed throughout mouse embryonic development, with the highest levels of expression in E7-E11. FISH and hybridization to mouse YACs confirmed human and mouse synteny in the order of this gene and other genes in the MLS critical region; however, this gene spans the boundary of the pseudoautosomal region in mouse but not in humans.


Subject(s)
Gene Expression Regulation, Developmental/physiology , Microphthalmos/genetics , Microtubule Proteins , Nuclear Proteins , Transcription Factors/genetics , X Chromosome/genetics , Zinc Fingers , Abnormalities, Multiple/genetics , Adult , Alternative Splicing , Animals , Cloning, Molecular , Exons/genetics , Female , Focal Dermal Hypoplasia/genetics , Genes, Regulator/genetics , Humans , Mice , Molecular Sequence Data , Organ Specificity , Physical Chromosome Mapping/methods , Sequence Analysis, DNA , Skin Abnormalities/genetics , Species Specificity , Syndrome , Ubiquitin-Protein Ligases
11.
Phys Rev Lett ; 92(11): 112301, 2004 Mar 19.
Article in English | MEDLINE | ID: mdl-15089125

ABSTRACT

Transverse mass and rapidity distributions for charged pions, charged kaons, protons, and antiprotons are reported for square root of [sNN]=200 GeV pp and Au+Au collisions at Relativistic Heary Ion Collider (RHIC). Chemical and kinetic equilibrium model fits to our data reveal strong radial flow and long duration from chemical to kinetic freeze-out in central Au+Au collisions. The chemical freeze-out temperature appears to be independent of initial conditions at RHIC energies.

12.
Phys Rev Lett ; 92(9): 092301, 2004 Mar 05.
Article in English | MEDLINE | ID: mdl-15089460

ABSTRACT

We report results on rho(770)(0)-->pi(+)pi(-) production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[s(NN)]=200 GeV. This is the first direct measurement of rho(770)(0)-->pi(+)pi(-) in heavy-ion collisions. The measured rho(0) peak in the invariant mass distribution is shifted by approximately 40 MeV/c(2) in minimum bias p+p interactions and approximately 70 MeV/c(2) in peripheral Au+Au collisions. The rho(0) mass shift is dependent on transverse momentum and multiplicity. The modification of the rho(0) meson mass, width, and shape due to phase space and dynamical effects are discussed.

13.
Phys Rev Lett ; 92(17): 171801, 2004 Apr 30.
Article in English | MEDLINE | ID: mdl-15169138

ABSTRACT

Measurements of the production of forward high-energy pi(0) mesons from transversely polarized proton collisions at sqrt[s]=200 GeV are reported. The cross section is generally consistent with next-to-leading order perturbative QCD calculations. The analyzing power is small at x(F) below about 0.3, and becomes positive and large at higher x(F), similar to the trend in data at sqrt[s]< or =20 GeV. The analyzing power is in qualitative agreement with perturbative QCD model expectations. This is the first significant spin result seen for particles produced with p(T)>1 GeV/c at a polarized proton collider.

14.
Phys Rev Lett ; 92(18): 182301, 2004 May 07.
Article in English | MEDLINE | ID: mdl-15169485

ABSTRACT

The transverse mass spectra and midrapidity yields for Xis and Omegas are presented. For the 10% most central collisions, the (-)Xi(+)/h(-) ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi(-)/h(-) stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi, K, p, and Lambdas.

15.
Phys Rev Lett ; 92(6): 062301, 2004 Feb 13.
Article in English | MEDLINE | ID: mdl-14995231

ABSTRACT

We report the first observations of the first harmonic (directed flow, v(1)) and the fourth harmonic (v(4)), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v(2)) generated at RHIC. From the correlation of v(2) with v(1) it is determined that v(2) is positive, or in-plane. The integrated v(4) is about a factor of 10 smaller than v(2). For the sixth (v(6)) and eighth (v(8)) harmonics upper limits on the magnitudes are reported.

16.
Phys Rev Lett ; 92(5): 052302, 2004 Feb 06.
Article in English | MEDLINE | ID: mdl-14995300

ABSTRACT

We present STAR measurements of the azimuthal anisotropy parameter v(2) and the binary-collision scaled centrality ratio R(CP) for kaons and lambdas (Lambda+Lambda) at midrapidity in Au+Au collisions at square root of s(NN)=200 GeV. In combination, the v(2) and R(CP) particle-type dependencies contradict expectations from partonic energy loss followed by standard fragmentation in vacuum. We establish p(T) approximately 5 GeV/c as the value where the centrality dependent baryon enhancement ends. The K(0)(S) and Lambda+Lambda v(2) values are consistent with expectations of constituent-quark-number scaling from models of hadron formation by parton coalescence or recombination.

17.
Phys Rev Lett ; 91(7): 072304, 2003 Aug 15.
Article in English | MEDLINE | ID: mdl-12935009

ABSTRACT

We report measurements of single-particle inclusive spectra and two-particle azimuthal distributions of charged hadrons at high transverse momentum (high p(T)) in minimum bias and central d+Au collisions at sqrt[s(NN)]=200 GeV. The inclusive yield is enhanced in d+Au collisions relative to binary-scaled p+p collisions, while the two-particle azimuthal distributions are very similar to those observed in p+p collisions. These results demonstrate that the strong suppression of the inclusive yield and back-to-back correlations at high p(T) previously observed in central Au+Au collisions are due to final-state interactions with the dense medium generated in such collisions.

18.
Phys Rev Lett ; 87(11): 112303, 2001 Sep 10.
Article in English | MEDLINE | ID: mdl-11531517

ABSTRACT

The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h(-)) in Au+Au interactions at square root of ([s(NN)]) = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dN(h(-))/d(eta)/(eta = 0) = 280+/-1(stat)+/-20(syst), an increase per participant of 38% relative to pp collisions at the same energy. The mean transverse momentum is 0.508+/-0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h(-) yield per participant is a strong function of p( perpendicular). The pseudorapidity distribution is almost constant within /eta/<1.

19.
Phys Rev Lett ; 87(8): 082301, 2001 Aug 20.
Article in English | MEDLINE | ID: mdl-11497937

ABSTRACT

Two-pion correlation functions in Au+Au collisions at square root of [s(NN)] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in square root of [s(NN)].

20.
Phys Rev Lett ; 87(26): 262302, 2001 Dec 24.
Article in English | MEDLINE | ID: mdl-11800830

ABSTRACT

We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at square root of s(NN) = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25

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