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3.
Pharmacogenomics J ; 10(3): 191-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20038957

RESUMO

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.


Assuntos
PPAR delta/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Sulfotransferases/genética , Taxoides/uso terapêutico , Talidomida/uso terapêutico , Adulto , Idoso , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Orquiectomia , Farmacogenética , Polimorfismo de Nucleotídeo Único , Taxoides/efeitos adversos , Taxoides/farmacocinética , Talidomida/efeitos adversos , Talidomida/farmacocinética , Carboidrato Sulfotransferases
5.
Phys Rev Lett ; 97(15): 152301, 2006 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-17155321

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-16007484

RESUMO

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.


Assuntos
Proteínas do Esmalte Dentário/genética , Esmalte Dentário/patologia , Proteínas Ativadoras de GTPase/genética , Deleção de Genes , Camundongos Transgênicos/genética , Amelogênese Imperfeita/genética , Amelogenina , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Dente/metabolismo , Dente/ultraestrutura
7.
Phys Rev Lett ; 94(6): 062301, 2005 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-15783724

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-16241721

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-9722948

RESUMO

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.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Microftalmia/genética , Proteínas dos Microtúbulos , Proteínas Nucleares , Fatores de Transcrição/genética , Cromossomo X/genética , Dedos de Zinco , Anormalidades Múltiplas/genética , Adulto , Processamento Alternativo , Animais , Clonagem Molecular , Éxons/genética , Feminino , Hipoplasia Dérmica Focal/genética , Genes Reguladores/genética , Humanos , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos , Mapeamento Físico do Cromossomo/métodos , Análise de Sequência de DNA , Anormalidades da Pele/genética , Especificidade da Espécie , Síndrome , Ubiquitina-Proteína Ligases
10.
Phys Rev Lett ; 91(26 Pt 1): 262301, 2003 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-14754043

RESUMO

Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[s(NN)]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.

11.
Phys Rev Lett ; 91(26 Pt 1): 262302, 2003 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-14754044

RESUMO

Pion-kaon correlation functions are constructed from central Au+Au STAR data taken at sqrt[s(NN)]=130 GeV by the STAR detector at the Relativistic Heavy Ion Collider (RHIC). The results suggest that pions and kaons are not emitted at the same average space-time point. Space-momentum correlations, i.e., transverse flow, lead to a space-time emission asymmetry of pions and kaons that is consistent with the data. This result provides new independent evidence that the system created at RHIC undergoes a collective transverse expansion.

13.
Phys Rev Lett ; 89(13): 132301, 2002 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-12225018

RESUMO

We report STAR results on the azimuthal anisotropy parameter v(2) for strange particles K(0)(S), Lambda, and Lambda at midrapidity in Au+Au collisions at sqrt[s(NN)]=130 GeV at the Relativistic Heavy Ion Collider. The value of v(2) as a function of transverse momentum, p(t), of the produced particle and collision centrality is presented for both particles up to p(t) approximately 3.0 GeV/c. A strong p(t) dependence in v(2) is observed up to 2.0 GeV/c. The v(2) measurement is compared with hydrodynamic model calculations. The physics implications of the p(t) integrated v(2) magnitude as a function of particle mass are also discussed.

14.
Phys Rev Lett ; 89(9): 092301, 2002 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-12190390

RESUMO

We report the first measurement of strange (Lambda) and antistrange (Lambda macro) baryon production from square root of [s(NN)]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda; hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda; hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.

15.
Phys Rev Lett ; 92(6): 062301, 2004 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-14995231

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-14995300

RESUMO

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 ; 92(9): 092301, 2004 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-15089460

RESUMO

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.

18.
Phys Rev Lett ; 90(3): 032301, 2003 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-12570484

RESUMO

Azimuthal anisotropy (v(2)) and two-particle angular correlations of high p(T) charged hadrons have been measured in Au+Au collisions at sqrt[s(NN)]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high p(T) partons. The monotonic rise of v(2)(p(T)) for p(T)<2 GeV/c is consistent with collective hydrodynamical flow calculations. At p(T)>3 GeV/c, a saturation of v(2) is observed which persists up to p(T)=6 GeV/c.

19.
Phys Rev Lett ; 91(7): 072304, 2003 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-12935009

RESUMO

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.

20.
Phys Rev Lett ; 93(25): 252301, 2004 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-15697893

RESUMO

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au + Au collisions at square root s(NN)=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 p + p at the same energy. The elliptic anisotropy v(2) is found to reach its maximum at p(t) approximately 3 GeV/c, then decrease slowly and remain significant up to p(t) approximately 7-10 GeV/c. Stronger suppression is found in the back-to-back high-p(t) particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v(2) at intermediate p(t) is compared to simple models based on jet quenching.

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