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1.
Nat Commun ; 14(1): 6143, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903790

RESUMO

Both solar wind and ionospheric sources contribute to the magnetotail plasma sheet, but how their contribution changes during a geomagnetic storm is an open question. The source is critical because the plasma sheet properties control the enhancement and decay rate of the ring current, the main cause of the geomagnetic field perturbations that define a geomagnetic storm. Here we use the solar wind composition to track the source and show that the plasma sheet source changes from predominantly solar wind to predominantly ionospheric as a storm develops. Additionally, we find that the ionospheric plasma during the storm main phase is initially dominated by singly ionized hydrogen (H+), likely from the polar wind, a low energy outflow from the polar cap, and then transitions to the accelerated outflow from the dayside and nightside auroral regions, identified by singly ionized oxygen (O+). These results reveal how the access to the magnetotail of the different sources can change quickly, impacting the storm development.

2.
Nat Commun ; 13(1): 6259, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307443

RESUMO

Electromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA's Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations.

3.
Geophys Res Lett ; 49(15): e2022GL099655, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36247517

RESUMO

Microbursts are impulsive (<1 s) injections of electrons into the atmosphere, thought to be caused by nonlinear scattering by chorus waves. Although attempts have been made to quantify their contribution to outer belt electron loss, the uncertainty in the overall size and duration of the microburst region is typically large, so that their contribution to outer belt loss is uncertain. We combine datasets that measure chorus waves (Van Allen Probes [RBSP], Arase, ground-based VLF stations) and microburst (>30 keV) precipitation (FIREBIRD II and AC6 CubeSats, POES) to determine the size of the microburst-producing chorus source region beginning on 5 December 2017. We estimate that the long-lasting (∼30 hr) microburst-producing chorus region extends from 4 to 8 Δ MLT and 2-5 Δ L. We conclude that microbursts likely represent a major loss source of outer radiation belt electrons for this event.

4.
Space Sci Rev ; 218(5): 38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757012

RESUMO

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts.

5.
Sci Rep ; 11(1): 13724, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257336

RESUMO

Pulsating aurorae (PsA) are caused by the intermittent precipitations of magnetospheric electrons (energies of a few keV to a few tens of keV) through wave-particle interactions, thereby depositing most of their energy at altitudes ~ 100 km. However, the maximum energy of precipitated electrons and its impacts on the atmosphere are unknown. Herein, we report unique observations by the European Incoherent Scatter (EISCAT) radar showing electron precipitations ranging from a few hundred keV to a few MeV during a PsA associated with a weak geomagnetic storm. Simultaneously, the Arase spacecraft has observed intense whistler-mode chorus waves at the conjugate location along magnetic field lines. A computer simulation based on the EISCAT observations shows immediate catalytic ozone depletion at the mesospheric altitudes. Since PsA occurs frequently, often in daily basis, and extends its impact over large MLT areas, we anticipate that the PsA possesses a significant forcing to the mesospheric ozone chemistry in high latitudes through high energy electron precipitations. Therefore, the generation of PsA results in the depletion of mesospheric ozone through high-energy electron precipitations caused by whistler-mode chorus waves, which are similar to the well-known effect due to solar energetic protons triggered by solar flares.

6.
Earth Planets Space ; 72(1): 111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831576

RESUMO

We investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass (M) up to 3-4 amu at L = 3.3-3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M. This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O+ density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H+ band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H+, 3.4% He+, and 16.0% O+. According to the linearized dispersion relation for EMIC waves, both He+ and O+ ions inhibit EMIC wave growth and the stabilizing effect is stronger for He+ than O+. Therefore, when the H+ fraction or M is constant, the denser O+ ions are naturally accompanied by the more tenuous He+ ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere.

7.
Sci Rep ; 10(1): 3380, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098993

RESUMO

The brightness of aurorae in Earth's polar region often beats with periods ranging from sub-second to a few tens of a second. Past observations showed that the beat of the aurora is composed of a superposition of two independent periodicities that co-exist hierarchically. However, the origin of such multiple time-scale beats in aurora remains poorly understood due to a lack of measurements with sufficiently high temporal resolution. By coordinating experiments using ultrafast auroral imagers deployed in the Arctic with the newly-launched magnetospheric satellite Arase, we succeeded in identifying an excellent agreement between the beats in aurorae and intensity modulations of natural electromagnetic waves in space called "chorus". In particular, sub-second scintillations of aurorae are precisely controlled by fine-scale chirping rhythms in chorus. The observation of this striking correlation demonstrates that resonant interaction between energetic electrons and chorus waves in magnetospheres orchestrates the complex behavior of aurora on Earth and other magnetized planets.

8.
Space Sci Rev ; 215(1): 9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880847

RESUMO

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

10.
Science ; 361(6406): 1000-1003, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30190400

RESUMO

Particle acceleration by plasma waves and spontaneous wave generation are fundamental energy and momentum exchange processes in collisionless plasmas. Such wave-particle interactions occur ubiquitously in space. We present ultrafast measurements in Earth's magnetosphere by the Magnetospheric Multiscale spacecraft that enabled quantitative evaluation of energy transfer in interactions associated with electromagnetic ion cyclotron waves. The observed ion distributions are not symmetric around the magnetic field direction but are in phase with the plasma wave fields. The wave-ion phase relations demonstrate that a cyclotron resonance transferred energy from hot protons to waves, which in turn nonresonantly accelerated cold He+ to energies up to ~2 kilo-electron volts. These observations provide direct quantitative evidence for collisionless energy transfer in plasmas between distinct particle populations via wave-particle interactions.

11.
Nature ; 554(7692): 337-340, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29446380

RESUMO

Auroral substorms, dynamic phenomena that occur in the upper atmosphere at night, are caused by global reconfiguration of the magnetosphere, which releases stored solar wind energy. These storms are characterized by auroral brightening from dusk to midnight, followed by violent motions of distinct auroral arcs that suddenly break up, and the subsequent emergence of diffuse, pulsating auroral patches at dawn. Pulsating aurorae, which are quasiperiodic, blinking patches of light tens to hundreds of kilometres across, appear at altitudes of about 100 kilometres in the high-latitude regions of both hemispheres, and multiple patches often cover the entire sky. This auroral pulsation, with periods of several to tens of seconds, is generated by the intermittent precipitation of energetic electrons (several to tens of kiloelectronvolts) arriving from the magnetosphere and colliding with the atoms and molecules of the upper atmosphere. A possible cause of this precipitation is the interaction between magnetospheric electrons and electromagnetic waves called whistler-mode chorus waves. However, no direct observational evidence of this interaction has been obtained so far. Here we report that energetic electrons are scattered by chorus waves, resulting in their precipitation. Our observations were made in March 2017 with a magnetospheric spacecraft equipped with a high-angular-resolution electron sensor and electromagnetic field instruments. The measured quasiperiodic precipitating electron flux was sufficiently intense to generate a pulsating aurora, which was indeed simultaneously observed by a ground auroral imager.

12.
JDR Clin Trans Res ; 3(2): 195-202, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-30931768

RESUMO

The purpose of the current study was to investigate the association between maximum occlusal force, which is an objective predictor of masticatory performance, and incident functional disability in an elderly Japanese population. A prospective cohort study was conducted targeting 815 (51.7% female) community-dwelling older adults aged ≥70 y residing in the Tsurugaya district, Sendai, Japan. The outcome measurement was incident functional disability, defined as a first certification of long-term care insurance in Japan, which is determined on the basis of a strictly established, uniform, nationwide standard. During a median follow-up of 7.9 y (interquartile range, 4.8-7.9 y), information on long-term care insurance was obtained from the Sendai Municipal Authority. Bilateral maximum occlusal forces of the participants were measured using a horseshoe-shaped pressure-indicating film, and the participants were categorized into quartiles based on occlusal force. Adjusted hazard ratios for functional disability were estimated with Cox proportional hazard models, adjusted for age, sex, body mass index, medical history, smoking status, alcohol consumption, duration of education, depressive symptoms, cognitive impairment, physical functioning, marital status, history of falls, and number of remaining teeth. The multiple-adjusted hazard ratios and 95% confidence intervals (CIs) for incident functional disability compared to the greatest occlusal force quartile were 1.53 (95% CI, 1.02-2.33), 1.64 (95% CI, 1.06-2.55), and 1.64 (95% CI, 1.01-2.68) for the third, second, and first quartiles, respectively ( P for trend = 0.011). A lower maximum occlusal force was significantly associated with an increased risk of functional disability independently of possible confounders, including the number of remaining teeth. Occlusal force may be a useful indicator of the relationship between oral function and geriatric health. Knowledge Transfer Statement:This prospective cohort study demonstrated that lower maximum occlusal force was associated with an increased risk of functional disability in older adults, even after adjustment for possible confounding factors, including the number of remaining teeth. This strengthens the rationale regarding the association between oral function and geriatric health. Particularly in older adults, occlusal force is reduced by several factors other than tooth loss, such as the absence of a dental prostheses, sarcopenia in the masticatory muscle, poor periodontal condition, and orofacial pain. Our findings suggest that maximum occlusal force may be a useful biomarker associated with diverse parameters aside from the number of remaining teeth.


Assuntos
Força de Mordida , Perda de Dente , Idoso , Feminino , Humanos , Vida Independente , Japão , Masculino , Estudos Prospectivos
13.
Andrology ; 5(2): 262-267, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27813361

RESUMO

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4 cm3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7 pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10 ng/mL.


Assuntos
Adenocarcinoma/diagnóstico , Di-Hidrotestosterona/sangue , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Espectrometria de Massas em Tandem , Testosterona/sangue
14.
Andrology ; 1(3): 505-11, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23444052

RESUMO

Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients' prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0 ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p < 0.01) and low concentration of tissue 5α-dihydrotestosterone (DHT) (p < 0.01), resulting in a higher tissue T/DHT ratio (p < 0.001). A multivariate Cox proportional hazard model revealed the pre-ADT tissue T/DHT ratio and Gleason score as independent predictors for CRPC development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/metabolismo , Orquiectomia , Próstata/metabolismo , Neoplasias da Próstata/etiologia , Idoso , Humanos , Masculino
15.
Public Health ; 124(9): 530-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20728909

RESUMO

OBJECTIVES: To investigate the effect of weight perception and lifestyle on body mass index (BMI) over a 2-year period. STUDY DESIGN: Longitudinal study to compare the change in BMI (kg/m(2)) according to weight perception and lifestyle at baseline. METHODS: Study subjects were 6029 men and 18,567 women aged 20-69 years who worked at a large financial firm in Japan. Subjects' weight and height were measured in 2004 and 2006. The data in 2004 were used as baseline data. Weight perception and lifestyle factors, including eating, physical exercise, hours of sleep, smoking and alcohol consumption, were determined by a self-administered questionnaire in 2004. RESULTS: The age-adjusted mean change in BMI over the 2-year period was -0.0593 among men and 0.0890 among women. In men, subjects who perceived themselves to be overweight had a reduced BMI 2 years later compared with subjects who perceived themselves to be 'just right' or underweight. Multiple regression analysis of lifestyle factors, adjusted for age and BMI at baseline, indicated that less time spent commuting, not having a hobby, not having a fixed lunch time, consumption of sweets, smoking and colleagues' smoking were associated with increased BMI among men. Fewer hours of sleep, no fixed lunch time and frequent soft drink consumption were associated with increased BMI among women. CONCLUSIONS: A perception of being overweight was associated with a decrease in BMI for Japanese male workers. Positive lifestyle factors associated with a decrease in BMI in both men and women include having a fixed lunch time and being older. These factors should therefore be highlighted in future health promotion activities in workplaces.


Assuntos
Imagem Corporal , Índice de Massa Corporal , Peso Corporal , Estilo de Vida , Adulto , Idoso , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
16.
Phys Rev Lett ; 102(22): 227201, 2009 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-19658897

RESUMO

The scaling exponent of 1.6 between anomalous Hall and longitudinal conductivity, characteristic of the universal Hall mechanism in dirty-metal ferromagnets, emerges from a series of CrO2 films as we systematically increase structural disorder. Magnetic disorder in CrO2 increases with temperature and this drives a separate topological Hall mechanism. We find that these terms are controlled discretely by structural and magnetic defect populations, and their coexistence leads to apparent divergence from exponent 1.6, suggesting that the universal term is more prevalent than previously realized.

17.
Rev Sci Instrum ; 79(7): 074901, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18681727

RESUMO

A new method of utilizing a commercial silicon nitride membrane calorimeter to measure the latent heat at a first order phase transition is presented. The method is a direct measurement of the thermoelectric voltage jump induced by the latent heat, in a thermally isolated system ideally suited for single crystal and small microgram samples. We show that when combined with the ac calorimetry technique previously developed, the resultant thermal measurement capabilities are extremely powerful. We demonstrate the applicability of the combined method with measurements on a 100 microm size fragment of CoMnSi exhibiting a sizable magnetocaloric effect near room temperature, and obtain good agreement with previously reported values on bulk samples.

18.
Clin Genet ; 73(6): 535-44, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18435794

RESUMO

Mandibuloacral dysplasia (MAD) is a rare autosomal recessive progeroid syndrome, characterized by mandibular hypoplasia, acroosteolysis affecting distal phalanges and clavicles, delayed closure of the cranial sutures, atrophic skin, and lipodystrophy. Recently, mutations in lamin A/C (LMNA) and zinc metalloprotease (ZMPSTE24), involved in post-translational processing of prelamin A to mature lamin A, have been identified in MAD kindreds. We now report novel compound heterozygous mutations in exon 1 (c.121C>T; p.Q41X) and exon 6 (c.743C>T; p.P248L) in ZMPSTE24 in two Japanese sisters, 7- and 3-year old, with severe MAD and characteristic facies and atrophic skin. The older sister had lipodystrophy affecting the chest and thighs but sparing abdomen. Their parents and a brother, who were healthy, had heterozygous mutations. The missense mutation, P248L, was not found in 100 normal subjects of Japanese origin. The mutant Q41X was inactive in a yeast halo assay; however, the mutant P248L retained near normal ZMPSTE24 activity. Immunoblots demonstrated accumulation of prelamin A in the patients' cell lysates from lymphoblasts. The lymphoblasts from the patients also revealed less intense staining for lamin A/C on immunofluorescence. We conclude that ZMPSTE24 deficiency results in accumulation of farnesylated prelamin A, which may be responsible for cellular toxicity and the MAD phenotype.


Assuntos
Anormalidades Múltiplas/genética , Mandíbula/anormalidades , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Mutação de Sentido Incorreto , Povo Asiático , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Lamina Tipo A , Lipodistrofia/genética , Proteínas de Membrana/deficiência , Metaloendopeptidases/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fenótipo , Prenilação , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Irmãos
19.
Eur J Surg Oncol ; 34(7): 734-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17764884

RESUMO

AIMS: It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes. MATERIAL AND METHODS: Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay. RESULTS: The mean tumor reduction rate for all patients (n=62) was significantly (p<0.001) higher in GSTP1 negative (0.73+/-0.04; mean+/-standard error) than GSTP1 positive (0.31+/-0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p=0.005) higher in GSTP1 negative (0.59+/-0.06) than GSTP1 positive (0.11+/-0.13) tumors in the docetaxel group as well as in the paclitaxel group (p=0.006; GSTP1 negative tumors: 0.84+/-0.05; GSTP1 positive tumors: 0.56+/-0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate. CONCLUSION: Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Glutationa S-Transferase pi/metabolismo , Paclitaxel/farmacologia , Taxoides/farmacologia , Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Metilação de DNA , Docetaxel , Feminino , Marcadores Genéticos , Glutationa S-Transferase pi/genética , Humanos , Imuno-Histoquímica , Paclitaxel/farmacocinética , Taxoides/farmacocinética
20.
Ann Oncol ; 19(1): 68-72, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17956886

RESUMO

BACKGROUND: We recently established a novel assay for specific activity (SA) of cyclin-dependent kinases (CDKs) using small tumor samples (>/=8 mm(3)). The aim of this study was to investigate the prognostic significance of CDK1SA and CDK2SA in human breast cancer. METHODS: CDK1SA and CDK2SA were determined in 284 breast cancer patients and their prognostic significance was investigated. RESULTS: Tumors with high CDK1SA and high CDK2SA showed significantly poorer 5-year relapse-free survival than those with low CDK1SA and low CDK2SA, respectively (66.9% vs 84.2% for CDK1SA; 43.6% vs 83.6% for CDK2SA). Moreover, combined analysis of CDK1SA and CDK2SA enabled the classification of breast tumors into high-risk and low-risk groups, where tumors in the high-risk group were strongly associated with unfavorable prognosis (5-year relapse-free survival 69.4% for the high-risk group and 91.5% for the low-risk group). Multivariate analysis showed that the risk determined by combined analysis of CDK1SA and CDK2SA is a significant (hazard ratio 3.09, P < 0.001) prognostic indicator for relapse, especially in node-negative patients (hazard ratio 6.73, P < 0.001). CONCLUSION: Determination of CDK1SA and CDK2SA may be useful in the prediction of outcomes in breast cancer patients and has potential for use as a routine laboratory test.


Assuntos
Neoplasias da Mama/enzimologia , Proteína Quinase CDC2/análise , Carcinoma Ductal de Mama/enzimologia , Quinase 2 Dependente de Ciclina/análise , Proteínas de Neoplasias/análise , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Estrogênios , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/enzimologia , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Risco
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