RESUMEN
In this study, we performed a year-long in situ incubation experiment on a common ferrous sulfide (Fe-S) mineral, pyrite, at the oxidative deep seafloor in the hydrothermal vent field in the Izu-Bonin arc, Japan, and characterized its microbiological and biogeochemical properties to understand the microbial alteration processes of the pyrite, focusing on Fe(II) oxidation. The microbial community analysis of the incubated pyrite showed that the domain Bacteria heavily dominated over Archaea compared with that of the ambient seawater, and Alphaproteobacteria and Gammaproteobacteria distinctively codominated at the class level. The mineralogical characterization by surface-sensitive Fe X-ray absorption near-edge structure (XANES) analysis revealed that specific Fe(III) hydroxides (schwertmannite and ferrihydrite) were locally formed at the pyrite surface as the pyrite alteration products. Based on the Fe(III) hydroxide species and proportion, we thermodynamically calculated the pH value at the pyrite surface to be pH 4.9 to 5.7, indicating that the acidic condition derived from pyrite alteration was locally formed at the surface against neutral ambient seawater. This acidic microenvironment at the pyrite surface might explain the distinct microbial communities found in our pyrite samples. Also, the acidity at the pyrite surface indicates that the abiotic Fe(II) oxidation rate was much limited at the pyrite surface kinetically, 3.9 × 103- to 1.6 × 105-fold lower than that in the ambient seawater. Moreover, nanoscale characterization of microbial biomolecules using carbon near-edge X-ray absorption fine-structure (NEXAFS) analysis showed that the sessile cells attached to pyrite excreted the acidic polysaccharide-rich extracellular polymeric substances at the pyrite surface, which can lead to the promotion of biogenic Fe(II) oxidation and pyrite alteration. IMPORTANCE Pyrite is one of the most common Fe-S minerals found in submarine hydrothermal environments. Previous studies demonstrated that the Fe-S mineral can be a suitable host for Fe(II)-oxidizing microbes in hydrothermal environments; however, the details of microbial Fe(II) oxidation processes with Fe-S mineral alteration are not well known. The spectroscopic and thermodynamic examination in the present study suggests that a moderately acidic pH condition was locally formed at the pyrite surface during pyrite alteration at the seafloor due to proton releases with Fe(II) and sulfidic S oxidations. Following previous studies, the abiotic Fe(II) oxidation rate significantly decreases with a decrease in pH, but the biotic (microbial) Fe(II) oxidation rate is not sensitive to the pH decrease. Thus, our findings clearly suggest that the pyrite surface is a unique microenvironment where abiotic Fe(II) oxidation is limited and biotic Fe(II) oxidation is more prominent than that in neutral ambient seawater.
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Compuestos Férricos , Compuestos Ferrosos , Hierro/química , Agua de Mar/microbiología , Sulfuros/química , Compuestos Férricos/química , Compuestos Ferrosos/química , Japón , MineralesRESUMEN
Soft X-ray spectromicroscopy was applied to study the quantitative distribution of DNA and protein in a mammalian chromosome at the spatial resolution of 100â¯nm. The quantities of DNA and protein were evaluated using 1s-π* transition in the NEXAFS spectra at the nitrogen K absorption edge. DNA was not uniformly distributed in the chromosome and DNA/protein ratio was less than 0.497. The present analysis revealed the clues to identify other molecules that contribute to the absorption spectrum of the sample. The results suggested that accumulation of the absorption spectra of relevant molecules would support the refinement of the analysis.
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Cromosomas de los Mamíferos/química , Animales , Células CHO , Línea Celular , Cricetulus , ADN/química , Estudios de Evaluación como Asunto , Microscopía Electrónica de Transmisión de Rastreo/métodos , Nitrógeno/química , Proteínas/química , Rayos XRESUMEN
Various synchrotron radiation-based spectroscopic and microscopic techniques are used to elucidate the room-temperature ferromagnetism of carbon-doped ZnO-nanowires (ZnO-C:NW) via a mild C+ ion implantation method. The photoluminescence and magnetic hysteresis loops reveal that the implantation of C reduces the number of intrinsic surface defects and increases the saturated magnetization of ZnO-NW. The interstitial implanted C ions constitute the majority of defects in ZnO-C:NW as confirmed by the X-ray absorption spectroscopic studies. The X-ray magnetic circular dichroism spectra of O and C K-edge respectively indicate there is a reduction in the number of unpaired/dangling O 2p bonds in the surface region of ZnO-C:NW and the C 2p-derived states of the implanted C ions strongly affect the net spin polarization in the surface and bulk regions of ZnO-C:NW. Furthermore, these findings corroborate well with the first-principles calculations of C-implanted ZnO in surface and bulk regions, which highlight the stability of implanted C for the suppression and enhancement of the ferromagnetism of the ZnO-C:NW in the surface region and bulk phase, respectively.
RESUMEN
Label-free detection of core-multishell (CMS) nanocarriers and the anti-inflammatory drug dexamethasone is reported. Selective excitation by tunable soft X-rays in the O 1s-regime is used for probing either the CMS nanocarrier or the drug. Furthermore, the drug loading efficiency into CMS nanocarriers is determined by X-ray spectroscopy. The drug-loaded nanocarriers were topically applied to human skin explants providing insights into the penetration and drug release processes. It is shown that the core-multishell nanocarriers remain in the stratum corneum when applied for 100min to 1000min. Dexamethasone, if applied topically to human ex vivo skin explants using different formulations, shows a vehicle-dependent penetration behavior. Highest local drug concentrations are found in the stratum corneum as well as in the viable epidermis. If the drug is loaded to core-multishell nanocarriers, the concentration of the free drug is low in the stratum corneum and is enhanced in the viable epidermis as compared to other drug formulations. The present results provide insights into the penetration of drug nanocarriers as well as the mechanisms of controlled drug release from CMS nanocarriers in human skin. They are also compared to related work using dye-labeled nanocarriers and dyes that were used as model drugs.
Asunto(s)
Dexametasona/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Nanopartículas , Administración Cutánea , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Transporte Biológico , Química Farmacéutica/métodos , Preparaciones de Acción Retardada , Dexametasona/farmacocinética , Liberación de Fármacos , Humanos , Microscopía de Fuerza Atómica/métodos , Piel/metabolismo , Absorción Cutánea , Factores de Tiempo , Espectroscopía de Absorción de Rayos X/métodosRESUMEN
This investigation studies the various magnetic behaviors of graphene oxide (GO) and reduced graphene oxides (rGOs) and elucidates the relationship between the chemical states that involve defects therein and their magnetic behaviors in GO sheets. Magnetic hysteresis loop reveals that the GO is ferromagnetic whereas photo-thermal moderately reduced graphene oxide (M-rGO) and heavily reduced graphene oxide (H-rGO) gradually become paramagnetic behavior at room temperature. Scanning transmission X-ray microscopy and corresponding X-ray absorption near-edge structure spectroscopy were utilized to investigate thoroughly the variation of the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups, as well as the C 2p(σ*)-derived states in flat and wrinkle regions to clarify the relationship between the spatially-resolved chemical states and the magnetism of GO, M-rGO and H-rGO. The results of X-ray magnetic circular dichroism further support the finding that C 2p(σ*)-derived states are the main origin of the magnetism of GO. Based on experimental results and first-principles calculations, the variation in magnetic behavior from GO to M-rGO and to H-rGO is interpreted, and the origin of ferromagnetism is identified as the C 2p(σ*)-derived states that involve defects/vacancies rather than the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups on GO sheets.
Asunto(s)
Grafito/química , Microscopía , Óxidos/química , Espectroscopía de Absorción de Rayos X , Microscopía/métodos , Modelos Teóricos , Espectroscopía de Absorción de Rayos X/métodosRESUMEN
Selective probing of dexamethasone in excised human skin using soft X-ray spectromicroscopy provides quantitative concentration profiles as well as two-dimensional drug distribution maps. Element- and site-selective excitation of dexamethasone at the oxygen K-edge with the lateral step width adjusted to 1 µm provides detailed information on the location of the drug in the different skin layers. The key of this work is to probe dexamethasone selectively at the carbonyl site (C3) by the O 1s â π* transition, providing also a most efficient way to quantify the drug concentration as a function of penetration depth in correlation with structural properties of the skin containing carboxyl and amide oxygen sites occurring at higher transition energy than dexamethasone. Following drug exposure for 4 h, the glucocorticoide is located in about equal amounts in the stratum corneum, the outermost horny layer of skin, and in the viable epidermis, whereas in the dermis no dexamethasone is detected. In the stratum corneum, most of the lipophilic drug is found in regions between corneocytes, where epidermal lipids are dominating.
Asunto(s)
Dexametasona/farmacocinética , Piel/química , Dexametasona/química , Voluntarios Sanos , Humanos , Conformación Molecular , Análisis Espectral , Rayos XRESUMEN
BACKGROUND: The cross-talk between Wnt signaling and the Akt pathway in prostate cancer (Pca) is still unclear. In the present study, we found that WIF-1 downregulates the Akt pathway and also enhances chemosensitivity in PTEN-null Pca cells. METHODS: Wnt inhibitory factor-1 (WIF-1), an inhibitor of Wnt proteins, was transfected into PC-3 and DU145 Pca cells. RESULTS: Akt was phosphorylated in PTEN-null PC-3 cells but underphosphorylated in PTEN-expressed DU145 cells. The levels of phosphorylated Akt in WIF-1 overexpressing PC-3 cells were lower than those in native or control vector-transfected PC-3 cells. However, WIF-1 showed no additional inhibition of already reduced Akt activity in DU145 cells. Overexpression of WIF-1 resulted in sensitizing PC-3 cells for paclitaxel to induce apoptosis. DU145 cells were more sensitive to paclitaxel but were not affected by WIF-1 transfection. The PI3K inhibitor LY294002 seemed to restore the chemosensitivity of native PC-3 cells like WIF-1 did. CONCLUSIONS: Our results show that Wnt signaling is involved in Akt activation in Pca cells. Our data also indicate the possibility that Wnt and its signaling pathway can be therapeutic targets for PTEN-mutated advanced Pca.
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Proteínas Portadoras/metabolismo , Resistencia a Antineoplásicos/fisiología , Neoplasias de la Próstata/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Represoras/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis , Proteínas Portadoras/genética , Línea Celular Tumoral , Proteínas del Citoesqueleto/metabolismo , Regulación hacia Abajo , Expresión Génica/fisiología , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Masculino , Mutación , Fosfohidrolasa PTEN , Paclitaxel/uso terapéutico , Monoéster Fosfórico Hidrolasas/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-akt , Proteínas Represoras/genética , Transducción de Señal/fisiología , Transactivadores/metabolismo , Transfección , Proteínas Supresoras de Tumor/genética , beta CateninaRESUMEN
BACKGROUND: Hypercalcemia is the most common of all paraneoplastic syndromes and has been reported to appear in up to 20% of patients with renal cell carcinoma (RCC). Humoral hypercalcemia of malignancy is believed to be induced when parathyroid hormone-related protein (PTHrP) is excessively produced in cancer cells and impairs the homeostasis of serum calcium concentrations. METHODS: Cancer cells were isolated from a surgical specimen and successfully cultured in a monolayer. The present study describes the establishment and characterization of new cell lines of RCC. RESULTS: Two different cell lines, designated SMRC-1 and SMRC-3, were established from human RCC, each of which had been continuously secreting PTHrP in vitro. The patient from whom the SMRC-3 cells were obtained was shown to have elevated levels of PTHrP and resultant hypercalcemia. Cultured SMRC-1 was spindle-shaped in morphology. SMRC-3 had pleomorphic polygonal shapes and formed typical epithelial monolayers. Both cell types secreted intact, C-terminal PTHrP and interleukin-6 in the culture medium. Cellular messenger RNA of PTHrP was analyzed by reverse transcriptase-polymerase chain reaction. The SMRC-1 cells showed chromosome numbers ranging from 42 to 47 with consistent structural abnormalities of add(4)(q23~25) and add(6)(q13). The chromosomal analysis of SMRC-3 revealed a modal number of 95 with consistent structural abnormalities of add(1)(p36) and der(1;3)(q10;p10). CONCLUSIONS: These cell lines could be good models for investigating the mechanism of PTHrP production and the relationship between this hormone and hypercalcemia.
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Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Biosíntesis de Proteínas , Células Tumorales Cultivadas/metabolismo , Adulto , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , División Celular , Aberraciones Cromosómicas , Cromosomas Humanos Par 1 , Humanos , Hipercalcemia/metabolismo , Interleucina-6/metabolismo , Cariotipificación , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Proteína Relacionada con la Hormona Paratiroidea , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas/citologíaRESUMEN
OBJECTIVE: To characterize a newly established human testicular carcinoma cell line that continuously produces alpha-fetoprotein (AFP), and to investigate the effects of retinoic acid on AFP production. MATERIALS AND METHODS: A 24-year-old man underwent a radical orchidectomy for a right testicular tumour and was found to have two separate metastatic lesions in the lungs, both of which were removed surgically. The cancer cells were isolated from one of the tumours, which was composed of undifferentiated germ cells and produced AFP; the cells were cultured in a monolayer. This cell line was designated as KU-MT. RESULTS: The cell line was successfully maintained both in athymic nude mice and in culture. Histological examination showed that the xenografted tumours were composed of cells in the reticular, solid and glandular patterns of a yolk sac tumour, and of embryonal carcinoma cells. These cells immunostained positively for AFP. On electron microscopy, the extracellular deposition of a basement lamina-like substance, a typical feature of yolk sac tumour, was detected. The AFP production in mice correlated well with the tumour weight of the xenograft. The cultured KU-MT cells were oval to polygonal in morphology and grew exponentially, with a population doubling time of approximately 2 days. Chromosomal analysis showed a modal number of 57 with consistent structural abnormalities of +add(1)(p13), del(1)(q32), del(2)(q31), add(6) (q21), +add(9)(p22), add(11)(p15), and add(14)(p11). Reverse-transcription polymerase chain reaction analysis showed that the retinoic acid receptors (RAR)-alpha, RAR-gamma, and retinoid X receptor-alpha were present in the cells. The expression of AFP mRNA was up-regulated in response to all-trans-retinoic acid; treatment with this agent caused morphological changes and induced apoptosis in the cells. CONCLUSIONS: This newly established cell line provides a reproducible model system that should offer a good insight into the differentiation of testicular carcinoma.
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Neoplasias Testiculares/metabolismo , Células Tumorales Cultivadas/metabolismo , alfa-Fetoproteínas/metabolismo , Adulto , Animales , Antineoplásicos/uso terapéutico , Northern Blotting , Humanos , Cariotipificación , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Desnudos , Infecciones por Mycoplasma/complicaciones , Trasplante de Neoplasias , Neoplasias Testiculares/patología , Tretinoina/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacos , alfa-Fetoproteínas/efectos de los fármacosRESUMEN
PURPOSE: Surgical removal remains the only potentially curative therapy for renal cell carcinoma. In this study we evaluated the inhibitory effect of the replication competent engineered herpes simplex virus type 1, G207, for renal cell carcinoma in vitro and in vivo. MATERIALS AND METHODS: The nature of G207 enables it to replicate within cancer cells, thus, causing cytolysis, but replication is restricted within normal cells. The susceptibility of the human renal cancer cell lines ACHN and A498 to G207 at a multiplicity of infection of 0.1 was examined. In addition, the growth characteristics of G207 was assessed. In vivo athymic mice bearing subcutaneous tumors were inoculated with 1 x 10(7) plaque forming units of G207 intra-neoplastically. For pathological analysis subcutaneous tumors were stained with X-gal. RESULTS: Two cell lines were efficiently destroyed by G207 within 1 week. The viral yields of G207 increased in a time dependent manner. In vivo the intra-neoplastic inoculation of G207 caused significantly decreased tumor growth in athymic mice harboring subcutaneous human renal cancer cells. On day 14 the mean growth ratio of ACHN and A498 lesions was significantly inhibited in G207 treated compared to control tumors (p <0.005 and <0.0001, respectively). CONCLUSIONS: These results suggest that G207 should be considered another potential therapeutic agent for renal cell carcinoma.
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Carcinoma de Células Renales/terapia , Terapia Genética/métodos , Vectores Genéticos , Herpesvirus Humano 1/genética , Neoplasias Renales/terapia , Animales , Ratones , Ratones Endogámicos BALB C , Células Tumorales Cultivadas , Replicación ViralRESUMEN
We report a case of aneurysmal-type renal arteriovenous fistula, which was successfully treated with transcatheter arterial embolization (TAE). A 73-year-old woman was referred to our hospital because of an incidental abnormal renal mass detected by computed tomography (CT). CT scan showed a round mass (4 x 3 x 3 cm) in the right kidney. Magnetic resonance (MR)-angiography and angiography revealed an aneurysmal type renal arteriovenous fistula (AVF). The patient was treated with TAE using detachable coils. CT, MR-angiography and angiography are useful means for the diagnosis of renal arteriovenous fistula. TAE is a powerful treatment for renal arteriovenous fistula.
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Aneurisma/diagnóstico por imagen , Fístula Arteriovenosa/terapia , Embolización Terapéutica , Arteria Renal , Venas Renales , Anciano , Fístula Arteriovenosa/diagnóstico por imagen , Embolización Terapéutica/métodos , Femenino , Humanos , RadiografíaRESUMEN
Over the last few years, a conditionally replicating herpes simplex virus 1 (HSV-1) vector, G207 has been used for the treatment of several malignant tumors. In this article we evaluate the anti-tumoral effect of G207 against prostate cancer in vitro and in vivo. The susceptibility of the human prostate cancer cell lines, DU145 and PC3 to G207 at a multiplicity of infection (MOI) of 0.1 was examined. In addition, the growth characteristics of G207 were assessed. Athymic mice with s.c. tumors were inoculated in vivo intraneoplastically with 1 x 10(7) plaque-forming units (PFU) of G207. For the pathological analyses, s.c. tumors were stained with X-gal. DU145 and PC3 were efficiently destroyed by G207 within 7 days. The viral yields of G207 increased time-dependently. In vivo, the intraneoplastic inoculation of G207 induced a significant inhibition of the tumor growth. The mean tumor growth ratio was significantly inhibited in the G207-treated tumors (DU145, P < 0.0001; PC3, P < 0.001 versus controls). In a pathological study, many lacZ-positive cells were diffusely present in the G207-treated tumors. G207 showed a significant antitumoral effect against human prostate cancer cell lines, and thus may be considered a useful agent for the treatment of prostate cancer.
Asunto(s)
Terapia Genética/métodos , Vectores Genéticos , Herpesvirus Humano 1/fisiología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Animales , División Celular , Herpesvirus Humano 1/genética , Humanos , Masculino , Ratones , Ratones Desnudos , Transfección , Células Tumorales Cultivadas , Replicación ViralRESUMEN
OBJECTIVES: To assess the prognostic significance of alkaline phosphatase (ALP) flare in 114 patients with metastatic prostate cancer treated with endocrine therapy. METHODS: ALP flare was defined as a transient increase of the serum ALP level to 120% or more of the pretreatment value after the initiation of endocrine therapy, followed by a subsequent decrease. RESULTS: Univariate analysis demonstrated that patients with poorly differentiated adenocarcinoma, an extent of disease of 2 or greater, a serum ALP level above twice the upper limit of normal, a serum prostate-specific antigen level greater than 100 ng/mL, an ALP flare, and a hemoglobin level of 12 g/dL or less had a significantly lower survival rate than their respective counterparts. Multivariate Cox's proportional hazards model analysis demonstrated that tumor histologic features and ALP flare were significant prognostic indicators for survival. CONCLUSIONS: The results of the present study suggest that the tumor histologic features and the ALP flare are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with endocrine therapy.
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Adenocarcinoma/enzimología , Adenocarcinoma/secundario , Fosfatasa Alcalina/sangre , Neoplasias de la Próstata/enzimología , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Castración , Estrógenos/uso terapéutico , Hormona Liberadora de Gonadotropina/uso terapéutico , Hemoglobinas/análisis , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
G207, a conditionally replicating herpes vector, efficiently kills human bladder cancer cells in vitro. To evaluate the therapeutic potential of G207, we have established three in vivo models similar to the clinical situation. In vivo, G207 was intraneoplastically, intravesically, or intravenously inoculated in nude mice. Intraneoplastic inoculation into subcutaneous tumor caused significant tumor growth inhibition. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited subcutaneous tumor growth. These results suggest that intravesical therapy with G207 is effective for localized bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy with G207 is promising for invasive or metastasized bladder tumor.
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Carcinoma in Situ/terapia , Técnicas de Transferencia de Gen , Terapia Genética , Simplexvirus/genética , Neoplasias de la Vejiga Urinaria/terapia , Animales , Carcinoma in Situ/patología , Carcinoma in Situ/secundario , Muerte Celular , Chlorocebus aethiops , Femenino , Vectores Genéticos , Humanos , Inyecciones Intralesiones , Inyecciones Intravenosas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/patología , Células VeroRESUMEN
BACKGROUND: Several methods for the identification of patients with prostate carcinoma have been proposed to enhance the clinical usefulness of prostate specific antigen (PSA). However, it remains unclear which method is superior in practical use. The authors attempted prospectively to identify the most powerful method with which to detect prostate carcinoma, especially among patients with intermediate PSA levels. METHODS: Between October 1997 and August 1999, systematic sextant biopsies were performed on 281 patients, including 147 with PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA density of the transition zone (PSATZD) for the detection of prostate carcinoma were compared by using receiver operating characteristic (ROC) curves and logistic regression analyses. RESULTS: According to ROC curve analysis, PSATZD had the greatest area under the curve in the overall patient population and in patients with intermediate PSA levels. In patients with intermediate PSA levels, at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68 of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25 patients, respectively. Stepwise logistic regression analysis showed that PSATZD and findings on digital rectal examination were significant independent predictors. CONCLUSIONS: PSATZD had the most useful validity in the differentiation between prostate carcinoma and benign prostatic enlargement in the overall patient population and in patients with intermediate PSA levels.
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Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata/metabolismo , Curva ROC , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.
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Biomarcadores de Tumor/sangre , Interleucina-6/sangre , Neoplasias de la Próstata/sangre , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Análisis de Varianza , Supervivencia sin Enfermedad , Hemoglobinas/análisis , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Tasa de SupervivenciaRESUMEN
Determination of the urinary steroid profile has been proposed as a sensitive tool for diagnosing adrenocortical tumors. The urinary steroid profiles were determined for patients with adrenocortical tumors. Urinary steroids were extracted, derivatized to form methyloxime-trimethylsilyl ether and analyzed by gas chromatography/mass spectrometry. Patients with adrenal adenomas from primary hyperaldosteronism had increased metabolites of 18-hydroxycorticosterone and aldosterone, and those with Cushing's syndrome had elevated excretion of 11 -deoxycortisol, cortisol, 18-hydroxycortisol, and cortisone metabolites. In patients with adrenocortical carcinomas, increased levels of metabolites of 11-deoxycortisol or 33-hydroxy-5-ene steroids were observed. The urinary steroid profiles of adrenal adenomas and adrenocortical carcinomas were quite different, suggesting the diagnostic validity for discriminating malignant from benign diseases.
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Adenoma/orina , Neoplasias de la Corteza Suprarrenal/orina , Carcinoma/orina , Esteroides/orina , Adenoma/complicaciones , Neoplasias de la Corteza Suprarrenal/complicaciones , Carcinoma/complicaciones , Síndrome de Cushing/orina , Diagnóstico Diferencial , Humanos , Hiperaldosteronismo/etiología , Hiperaldosteronismo/orinaRESUMEN
A case of bladder cancer with simultaneous production of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) is reported. An 81-year-old male patient was admitted to the Saitama Medical School for treatment of gross hematuria, leukocytosis and hypercalcemia and diagnosed as having advanced bladder cancer. Immediately after a cystectomy was carried out, his white cell count and serum calcium levels returned to normal. However, the tumors recurred locally and the recurrence was accompanied by an increase in the serum G-CSF and PTHrP levels with a recurrent elevation of white cell count and the serum calcium level. The production of G-CSF and PTHrP in the tumor cells was confirmed by immunohistochemistry.
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Factor Estimulante de Colonias de Granulocitos/biosíntesis , Proteínas de Neoplasias/biosíntesis , Biosíntesis de Proteínas , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Proteína Relacionada con la Hormona ParatiroideaRESUMEN
The signal transduction pathway showing how androgen withdrawal induces apoptosis in androgen-dependent cells has not been clearly understood. In these studies, we focused on the behavior of tyrosine kinases in androgen-dependent cells and investigated its correlation with apoptosis and bcl-2 expression. We used SC2G, an androgen-dependent mouse mammary carcinoma cell line, which had been cloned from Shionogi Carcinoma 115 (SC115). When SC2G cells were cultured with herbimycin A (HMA), a potent tyrosine kinase inhibitor, the number of viable cells decreased significantly after 24 h. Terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling and flow cytometric analysis of annexin V staining showed that HMA induced apoptosis of SC2G cells. The level of bcl-2 mRNA in SC2G cells was suppressed by HMA in a dose-dependent manner on RT-PCR. Preincubation with caspase inhibitors protected HMA-induced apoptosis of SC2G cells. When a human bcl-2 gene was transfected in SC2G cells and overexpressed, SC2G cells seemed to acquire tolerance for HMA. These data indicate that HMA-sensitive tyrosine kinase(s) can regulate apoptosis and inhibit bcl-2 expression in SC2G mouse androgen-dependent cells. Tyrosine kinase(s) seemed to be a member of signal transduction between androgen receptor activation and bcl-2 expression.
Asunto(s)
Apoptosis/fisiología , Hormonas Esteroides Gonadales/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Testosterona/farmacología , Animales , Apoptosis/efectos de los fármacos , Benzoquinonas , Caspasas/metabolismo , Separación Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Inhibidores de Cisteína Proteinasa/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Etiquetado Corte-Fin in Situ , Lactamas Macrocíclicas , Neoplasias Mamarias Experimentales , Ratones , Oligopéptidos/farmacología , Proteínas Tirosina Quinasas/metabolismo , Quinonas/farmacología , ARN Mensajero/análisis , Rifabutina/análogos & derivados , Transfección , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/enzimologíaRESUMEN
Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.