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Isotope imaging is commonly used to investigate the localization of trace elements and their isotopes. In situ noble gas analysis of meteorites revealed the distribution of primordial noble gases that were trapped in the building blocks of asteroids and planets during the early stage of the solar system evolution. Solar wind noble gases are among the primordial gases present in meteorites and were trapped through exposure to solar wind. Micrometer-resolution in situ noble gas analysis has not been achieved due to the lack of sensitivity and spatial resolution. The microscale imaging technique is crucial for identifying the carrier phase of the solar wind noble gases. We have developed 4He isotope imaging utilizing secondary neutral mass spectrometry with strong field postionization. This technique achieved a lateral resolution of 2 µm and a 4He detection limit of 2 × 1017 cm-3. This development allows for the study of a solar wind gas-rich meteorite, Northwest Africa 801 carbonaceous chondrite, with micrometer resolution. The solar wind 4He carriers are fine-grained particles and are sparsely scattered in the matrix region.
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Cation tracer diffusion in polycrystalline cubic BaZrO3 perovskites was studied using the stable isotopes 134Ba and 96Zr in air at 1015-1200 and 1300-1500 °C, respectively. Thin films of 134BaO and 96ZrO2 were deposited on polished BaZrO3 pellets by drop casting of aqueous precursor solutions containing the tracers. Isotope distribution profiles were recorded using secondary ion mass spectrometry. All the depth profiles exhibited two distinct regions, which enabled the assessment of both lattice and grain boundary diffusion using Fick's second law and Whipple-Le Clair's equation. The grain boundary diffusion of both cations was several orders of magnitude higher than the lattice diffusion. The lattice diffusion of Ba2+ was found to be significantly faster than the lattice diffusion of Zr4+, while the activation energies were comparable, respectively 395 ± 44 and 435 ± 67 kJ mol-1. Activation energies for the diffusion of Ba2+ and Zr4+ through a Ba2+ vacancy were calculated by density functional theory using the nudged elastic band method. The calculated and experimental activation energies were in excellent agreement. The cation diffusion data in BaZrO3 are compared to previous data on A and B-site diffusivity in perovskites. Finally, the diffusivity of Zr4+ in compounds with perovskite and fluorite crystal structures is discussed in relation to the chemical stability of BaZrO3-based materials.
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Cancer stem cells (CSCs) drive tumor initiation and metastasis in several types of human cancer. However, the contribution of ovarian CSCs to peritoneal metastasis remains unresolved. The cell adhesion molecule CD44 has been identified as a major marker for CSCs in solid tumors, including epithelial ovarian cancer. CD44 exists as a standard form (CD44s) and also as numerous variant isoforms (CD44v) generated by alternative mRNA splicing. Here we show that disseminated ovarian tumors in the pelvic peritoneum contain highly enriched CD44v6-positive cancer cells, which drive tumor metastasis and are responsible for tumor resistance to chemotherapy. Clinically, an increased number of CD44v6-positive cancer cells in primary tumors was associated with a shortened overall survival in stage III-IV ovarian cancer patients. Furthermore, a subpopulation of CD44v6-positive cancer cells manifested the ability to initiate tumor metastasis in the pelvic peritoneum in an in vivo mouse model, suggesting that CD44v6-positive cells show the potential to serve as metastasis-initiating cells. Thus, the peritoneal disseminated metastasis of epithelial ovarian cancer is initiated by the CD44v6-positive subpopulation, and CD44v6 expression is a biomarker for the clinical outcome of advanced ovarian cancer patients. Given that a distinct subpopulation of CD44v6-positive cancer cells plays a critical role in peritoneal metastasis, definitive treatment should target this subpopulation of CD44v6-positive cells in epithelial ovarian cancer.
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Receptores de Hialuranos/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Células Madre Neoplásicas/patología , Neoplasias Ováricas/patología , Neoplasias Peritoneales/secundario , Peritoneo/patología , Animales , Biomarcadores de Tumor/metabolismo , Cadherinas/biosíntesis , Carcinoma Epitelial de Ovario , Adhesión Celular/fisiología , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal/fisiología , Femenino , Fibronectinas/biosíntesis , Humanos , Receptores de Hialuranos/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/mortalidad , Ovario/patología , Resultado del Tratamiento , Vimentina/biosíntesisRESUMEN
Spontaneous rupture of an ovarian artery aneurysm most commonly presents with abdominal pain in a multiparous woman in the early post-partum period. Aneurysms of the ovarian artery have been reported in the published work very infrequently. In our case, a 31-year-old multiparous woman experienced sudden left lower quadrant abdominal pain on the second post-partum day. Angiography showed rupture of a left ovarian artery aneurysm, which was successfully embolized using gelatin sponge particles. The patient resumed menstruation 3 months after the embolization and concurrently conceived, ultimately giving birth at term without complications. Interventional radiology appears to be a highly safe and effective technique for diagnosis and management of a ruptured ovarian artery aneurysm with minimal risk of impairing subsequent fertility.
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Dolor Abdominal/terapia , Aneurisma Roto/terapia , Embolización Terapéutica/métodos , Ovario/irrigación sanguínea , Periodo Posparto , Dolor Abdominal/etiología , Adulto , Aneurisma Roto/complicaciones , Femenino , Humanos , Resultado del TratamientoRESUMEN
A two-tier system in which ovarian epithelial carcinomas are subdivided into type I and type II tumors has been proposed on the basis of recent molecular pathogenesis findings. Type I tumors, unrelated to tumor protein p53 (TP53) mutations, show favorable prognosis in a slow step-wise process, whereas type II tumors, related to TP53 mutations, contribute to poor prognosis. Ovarian serous carcinomas with excessive psammoma bodies behave like type I tumors. However, their etiology and prognostic significance remain obscure. The objective of the present study was to evaluate the characteristic features and potential relevance of psammoma bodies to the clinical outcome of 44 patients with serous carcinomas with long-term follow-up. The 5- and 10-year survival rates were significantly different between the serous carcinomas with less than 5% area of psammoma bodies and those at least 5% area (P < 0.01). All tumors with at least 5% area were both diploid and immunohistochemically negative for TP53 mutations. All patients with these tumors, including eight with International Federation of Gynecology and Obstetrics (FIGO) stages III or IV disease, survived more than 5 years and their 10-year survival rate was 76%. In multivariate analysis using clinical parameters, the apparent existence of psammoma bodies was an indication to view serous carcinomas as type I tumors with long-term survival. Our results suggested that the formation of psammoma bodies is associated with increased apoptotic tumor cell death related to normal TP53 function. The pathological findings of psammoma bodies might contribute to the consideration of pathogenesis and to the development of prognostic prediction rules for serous carcinomas.
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Cistadenocarcinoma Seroso/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Seroso/etiología , Cistadenocarcinoma Seroso/mortalidad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/etiología , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/etiología , Neoplasias Ováricas/mortalidad , Pronóstico , Tasa de SupervivenciaRESUMEN
Solvothermal deposition of ZnO layers on the c(±)-surfaces of ZnO single crystal substrates in a water-ethylene glycol solvent was investigated. Homoepitaxial growth of nanoparticulate layers was observed on the c(+)-surface. The manner of nanoparticle deposition on the c(+)-surface was similar to that of spherical particles precipitated in the solution, in that both grew through the oriented attachment of small particles during the early growth stage. The growth of the nanoparticulate film on the c(-)-surface was much slower than that on the c(+)-surface. After aging, the top surface of the film on the c(+)-surface transformed into a layer of pyramid-like particles so that the base of the pyramids was directed toward the surface. In contrast, randomly oriented pyramidal particles covered the c(-)-surface. Ostwald ripening through dissolution-recrystallization transformed the nanoparticles into pyramid-shaped particles in the latter stage when they were in contact with the solution. The faster growth on the c(+)-surface than on the c(-)-surface and the pyramidal shape of the particles with c(+)-basal plane deposited on the c(±)-surfaces after aging confirmed that the growth of the c(+)-plane was promoted, whereas the growth of {101Ì 0} and c(-)-planes was inhibited in this solution.
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Metal oxide semiconductor gas sensors have been widely studied for the selective detection of various gases with trace concentrations. The identification of the reaction scheme governing the gas sensing response is crucial for further development; however, the mechanism of ethanol (EtOH) gas sensing by ZnO is still controversial despite being one of the most intensively studied target gas and sensing material combinations. In this work, for the first time, the detailed mechanism of EtOH sensing by ZnO is studied by using a bulk single-crystalline substrate, which has a well-defined stoichiometry and atomic arrangement, as the sensing material. The sensing response is substantial on the ZnO substrate even with a millimeter-size thickness, and it becomes larger with resistance of the substrate. The large sensing response is described in terms of the adsorption/desorption of the oxygen species on the substrate surface, namely, oxygen ionosorption. The valence state of the ionosorbed oxygen involved in EtOH sensing is identified to be O2- regardless of the temperature. The increase in the sensing response with the temperature is attributed to the enhanced oxidation rate of the EtOH molecule on the surface as analyzed by pulsed-jet temperature-programmed desorption mass spectrometry, which has been newly developed for analyzing surface reactions in simulated working conditions.
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Scandium nitride (ScN) films were grown on α-Al2O3( 1 1 ¯ 02 ) substrates using the molecular beam epitaxy method, and the heteroepitaxial growth of ScN on α-Al2O3( 1 1 ¯ 02 ) and their electric properties were studied. Epitaxial ScN films with an orientation relationship (100)ScN || ( 1 1 ¯ 02 )α-Al2O3 and [001]ScN || [ 11 2 ¯ 0 ]α-Al2O3 were grown on α-Al2O3( 1 1 ¯ 02 ) substrates. Their crystalline orientation anisotropy was found to be small. In addition, [100] of the ScN films were tilted along [ 1 ¯ 101 ] of α-Al2O3( 1 1 ¯ 02 ) in the initial stage of growth. The tilt angle between the film growth direction and [100] of ScN was 1.4â»2.0° and increased with growth temperature. The crystallinity of the ScN films also improved with the increasing growth temperature. The film with the highest Hall mobility was obtained at the boundary growth conditions determined by the relationship between the crystallinity and the nonstoichiometric composition because the film with the highest crystallinity was obtained under the Sc-rich growth condition. The decreased Hall mobility with a simultaneous improvement in film crystallinity was caused by the increased carrier scattering by the ionized donors originating from the nonstoichiometric composition.
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The relationship between the diffusion behavior of hydrogen and the electrical properties of (Ba, Sr)TiO3 (BST) thin-film capacitors was investigated using thermal desorption spectroscopy and secondary ion mass spectroscopy analyses. It has been clearly shown that the frequency dependence of the complex impedance profile of the BST thin-film capacitors could be successfully represented by two parallel resistor-capacitor (RC) electrical equivalent networks in series correlated with the distribution of the hydrogen, namely, the Pt/BST interface region with the influence of hydrogen and the BST bulk region without the influence of hydrogen. However, the I-V properties of the BST thin-film capacitors could be determined almost from the hydrogen atoms existing at the Pt/BST interface.
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We developed a highly hydrogen-sensitive thermal desorption spectroscopy (HHS-TDS) system to detect and quantitatively analyze low hydrogen concentrations in thin films. The system was connected to an in situ sample-transfer chamber system, manipulators, and an rf magnetron sputtering thin-film deposition chamber under an ultra-high-vacuum (UHV) atmosphere of â¼10-8 Pa. The following key requirements were proposed in developing the HHS-TDS: (i) a low hydrogen residual partial pressure, (ii) a low hydrogen exhaust velocity, and (iii) minimization of hydrogen thermal desorption except from the bulk region of the thin films. To satisfy these requirements, appropriate materials and components were selected, and the system was constructed to extract the maximum performance from each component. Consequently, â¼2000 times higher sensitivity to hydrogen than that of a commercially available UHV-TDS system was achieved using H+-implanted Si samples. Quantitative analysis of an amorphous oxide semiconductor InGaZnO4 thin film (1 cm × 1 cm × 1 µm thickness, hydrogen concentration of 4.5 × 1017 atoms/cm3) was demonstrated using the HHS-TDS system. This concentration level cannot be detected using UHV-TDS or secondary ion mass spectroscopy (SIMS) systems. The hydrogen detection limit of the HHS-TDS system was estimated to be â¼1 × 1016 atoms/cm3, which implies â¼2 orders of magnitude higher sensitivity than that of SIMS and resonance nuclear reaction systems (â¼1018 atoms/cm3).
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Epithelial ovarian cancer is a highly lethal malignancy; moreover, overcoming chemoresistance is the major challenging in treating ovarian cancer patients. The cancer stem cell (CSC) hypothesis considers CSCs to be the main culprits in driving tumor initiation, metastasis, and resistance to conventional therapy. Although growing evidence suggest that CSCs are responsible for chemoresistance, the contribution of CSC marker EpCAM to resistance to chemotherapy remains unresolved.Here we have demonstrated that ovarian cancers containing high levels of EpCAM have a significantly much lower probability of achieving overall responsive rates after first-line chemotherapy. In addition, multivariate analysis revealed that EpCAM expression is an independent risk factor for chemoresistance, indicating that EpCAM expression is a predictive biomarker of chemotherapeutic response. Consistent with these clinical observations, in vitro assays, we found that the subpopulation of EpCAM-positive ovarian cancer cells shows a significantly higher viability compared with EpCAM-negative cells in response to cisplatin treatment by preventing chemotherapy-induced apoptosis, which is regulated by EpCAM-Bcl-2 axis. Furthermore, in an in vivo mouse model, platinum agents preferentially eliminated EpCAM-negative cells in comparison with EpCAM-positive cells, suggesting that the remaining subpopulation of EpCAM-positive cells contributes to tumor recurrence after chemotherapy. Finally, we also found that an increased expression of EpCAM is associated with poor prognosis in ovarian cancer patients.Our findings highlight the clinical significance of EpCAM in the resistance to chemotherapy and provide a rationale for EpCAM-targeted therapy to improve chemoresistance. Targeting EpCAM should be a promising approach to effectively extirpate the CSCs as the putative root of ovarian cancer.
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Molécula de Adhesión Celular Epitelial/genética , Expresión Génica , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/genética , Biomarcadores de Tumor , Carcinoma Epitelial de Ovario , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/patología , Oportunidad Relativa , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Pronóstico , Retratamiento , Factores de Riesgo , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto JovenRESUMEN
OBJECTIVE: The Japan Society of Gynecologic Oncology (JSGO) published the first practice guideline for endometrial cancer in 2006. The JSGO guideline evaluation committee assessed the effect of this guideline introduction on clinical practice and patient outcome using data provided by the Japan Society of Obstetrics and Gynecology (JSOG) cancer registration system. METHODS: Data of patients with endometrial cancer registered between 2000 and 2012 were analyzed, and epidemiological and clinical trends were assessed. The influence of guideline introduction on survival was determined by analyzing data of patients registered between 2004 and 2009 using competing risk model. RESULTS: In total, 65,241 cases of endometrial cancer were registered. Total number of patients registered each year increased about 3 times in the analyzed period, and the proportion of older patients with type II endometrial cancer rapidly increased. The frequency of lymphadenectomy had decreased not only among the low-recurrence risk group but also among the intermediate- or high-recurrence risk group. Adjuvant therapy was integrated into chemotherapy (p<0.001). Overall survival did not significantly differ before and after the guideline introduction (hazard ratio [HR]=0.891; p=0.160). Additional analyses revealed patients receiving adjuvant chemotherapy showed better prognosis than those receiving adjuvant radiation therapy when limited to stage I or II (HR= 0.598; p=0.003). CONCLUSION: It was suggested that guideline introduction influenced the management of endometrial cancer at several aspects. Better organized information and continuous evaluation are necessary to understand the causal relationship between the guideline and patient outcome.
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Adenocarcinoma de Células Claras/terapia , Carcinoma Endometrioide/terapia , Neoplasias Endometriales/terapia , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Sistema de Registros , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Quimioterapia Adyuvante/estadística & datos numéricos , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía , Japón , Escisión del Ganglio Linfático/estadística & datos numéricos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Quísticas, Mucinosas y Serosas/patología , Evaluación de Resultado en la Atención de Salud , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante/estadística & datos numéricos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
A gas analytical technique with compact size, low cost, sufficient sensitivity, and excellent reproducibility is required in many fields including exhaled breath analysis for medical monitoring. In the present study, we examined selective acetone concentration by quench condensation at cryogenic temperature followed by temperature programmed desorption (cryogenic temperature programmed desorption (cryo-TPD)) for possible applications to breath analysis for medical monitoring. The essence of cryo-TPD is rough mass selection by thermal desorption followed by quantification of certain species using mass spectrometry. The performance of cryo-TPD was investigated in the acetone concentration range below 1 × 10(-6) volume fraction (1 ppmv). It was found that acetone is selectively quench-condensed on a tungsten substrate at 50 K without the major components of air, such as N2 and O2. The concentrated acetone gas was obtained by the following thermal desorption at around 151 K. Under conditions of condensation for 1 min and pressure of 1 × 10(-2) Pa, the lowest limit of detection reached well below 10 × 10(-9) volume fraction (10 ppbv). The relationship between the cetone intensity of cryo-TPD and the acetone concentration in the gas was almost linear in the ppbv range. The separation of acetone and propanal using the fragmentation pattern, which have almost the identical molecular mass, was also demonstrated in the present study.
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Selective concentration of ultra-trace components in air-like gases has an important application in analyzing volatile organic compounds in the gas. In the present study, we examined quench-condensation of the sample gas on a ZnO substrate below 50 K followed by temperature programmed desorption (TPD) (low temperature TPD) as a selective gas concentration technique. We studied two specific gases in the normal air; krypton as an inert gas and acetone as a reactive gas. We evaluated the relationship between the operating condition of low temperature TPD and the lowest detection limit. In the case of krypton, we observed the selective concentration by exposing at 6 K followed by thermal desorption at about 60 K. On the other hand, no selectivity appeared for acetone although trace acetone was successfully concentrated. This is likely due to the solvent effect by a major component in the air, which is suggested to be water. We suggest that pre-condensation to remove the water component may improve the selectivity in the trace acetone analysis by low temperature TPD.
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OBJECTIVE: To investigate the role of cancer stem cell marker CD44 variant 6 in the development of distant metastasis in patients with epithelial ovarian cancer. METHODS: A retrospective cohort study was performed in 186 patients who underwent surgery for ovarian cancer from 2005 to 2013 at the Kumamoto University Hospital. The association between the expression of CD44 variant 6 and distant metastasis was evaluated based on a large-scale immunohistochemical analysis. Primary ovarian tumors that contained at least 10% CD44 variant 6-positive cancer cells were categorized as CD44v6-high (n=53), and the tumors that contained less than 10% CD44 variant 6-positive cells were categorized as CD44v6-low (n=133). Distant metastasis-free survival was compared between the CD44v6-high and -low groups. Multivariate analysis was performed to estimate the influence of various clinicopathologic factors on the development of distant metastasis. RESULTS: At the time of ovarian cancer diagnosis, distant metastasis occurred in 13 of 53 patients (24.5%) in the CD44v6-high group and 17 of 133 patients (12.8%) in the CD44v6-low group (P=.049). The median metastasis-free survival after stage I-III ovarian cancer diagnosis was 19.5 months (range 11-55 months) in the CD44v6-high group (n=40) and 39.5 months (range 22-57 months) in the CD44v6-low group (n=116) (P=.071). Multivariate analysis demonstrated that CD44 variant 6 expression was an independent risk factor for distant metastatic recurrence (hazard ratio 4.09, 95% confidence interval 1.29-12.98; P=.017). CONCLUSION: CD44 variant 6 represents an important predictor of distant metastasis and CD44 variant 6-positive ovarian cancer cells play a crucial role in the formation of distant metastases in patients with ovarian cancer.
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Biomarcadores de Tumor/metabolismo , Receptores de Hialuranos/metabolismo , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Japón/epidemiología , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.