Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 94
Filtrar
1.
Angiology ; 74(9): 832-839, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36056535

RESUMEN

Kawasaki disease (KD) is an acute systemic vascular disease complicated by coronary artery injury. Although polymorphisms in prostaglandin-endoperoxide synthase 1 (PTGS1) are being increasingly explored in cardiovascular diseases, little is known regarding the connection between PTGS1 polymorphisms and KD risk. We evaluated 834 KD patients and 1474 healthy controls to explore the relationship between PTGS1 polymorphisms (rs1330344 and rs5788) and KD risk. Our results showed that the rs1330344 CC genotype was significantly associated with KD risk and coronary artery injury in children with KD. In combined analysis, individuals with 1-2 unfavorable genotypes had an increased risk of KD, compared with those with no risk genotype. Stratified analysis indicated that the rs1330344 CC genotype is strongly associated with increased risk of KD in children aged ≤60 months and females. Moreover, carrying 1-2 of these SNP genotypes had a higher risk of KD than those who harbored none of them in children ≤60 months of age and females; the risk of coronary artery dilatations/small aneurysms and medium/giant aneurysms was also significantly increased in KD patients. In summary, the PTGS1 rs1330344 CC genotype is associated with increased susceptibility to KD, which may contribute to KD pathogenesis and serve as a genetic biomarker.


Asunto(s)
Aneurisma Coronario , Ciclooxigenasa 1 , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Aneurisma Coronario/complicaciones , Vasos Coronarios/patología , Ciclooxigenasa 1/genética , Pueblos del Este de Asia , Predisposición Genética a la Enfermedad , Genotipo , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/complicaciones , Polimorfismo de Nucleótido Simple
2.
J Clin Invest ; 130(9): 4679-4693, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32497024

RESUMEN

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.


Asunto(s)
Biomarcadores de Tumor/inmunología , Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica/inmunología , Neoplasias Hepáticas , Células Mieloides , Sorafenib/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Células Mieloides/inmunología , Células Mieloides/patología , Tasa de Supervivencia
3.
J Biol Chem ; 294(37): 13740-13754, 2019 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-31346035

RESUMEN

Seminal amyloid fibrils are made up of naturally occurring peptide fragments and are key targets for the development of combination microbicides or antiviral drugs. Previously, we reported that the polysulfonic compound ADS-J1 is a potential candidate microbicide that not only inhibits HIV-1 entry, but also seminal fibrils. However, the carcinogenic azo moieties in ADS-J1 preclude its clinical application. Here, we screened several ADS-J1-like analogs and found that the antiparasitic drug suramin most potently inhibited seminal amyloid fibrils. Using various biochemical methods, including Congo red staining, CD analysis, transmission EM, viral infection assays, surface plasmon resonance imaging, and molecular dynamics simulations, we investigated suramin's inhibitory effects and its putative mechanism of action. We found that by forming a multivalent interaction, suramin binds to proteolytic peptides and mature fibrils, thereby inhibiting seminal fibril formation and blocking fibril-mediated enhancement of viral infection. Of note, suramin exhibited potent anti-HIV activities, and combining suramin with several antiretroviral drugs produced synergistic effects against HIV-1 in semen. Suramin also displayed a good safety profile for vaginal application. Moreover, suramin inhibited the semen-derived enhancer of viral infection (SEVI)/semen-mediated enhancement of HIV-1 transcytosis through genital epithelial cells and the subsequent infection of target cells. Collectively, suramin has great potential for further development as a combination microbicide to reduce the spread of the AIDS pandemic by targeting both viral and host factors involved in HIV-1 sexual transmission.


Asunto(s)
Amiloide/efectos de los fármacos , Semen/efectos de los fármacos , Suramina/farmacología , Adulto , Animales , Fármacos Anti-VIH/farmacología , Antirretrovirales/farmacología , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Voluntarios Sanos , Humanos , Masculino , Fragmentos de Péptidos/metabolismo , Péptidos/metabolismo , Conejos , Semen/metabolismo , Suramina/metabolismo
4.
Gastroenterol Rep (Oxf) ; 7(1): 57-66, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30792867

RESUMEN

BACKGROUND AND OBJECTIVE: Biomarkers are important tools for prompt diagnosis of cancer. This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node (LN) metastasis. METHODS: Between 1 December 2014 and 31 December 2015, we prospectively collected samples of gastric-cancer tissues, corresponding matched-pair normal gastric mucosa, and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction. Relative quantity (RQ) was used to calculate the mRNA expression levels of our target genes. Statistics were calculated using one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Analytical graphs were plotted using GraphPad Prism. RESULTS: Of nine assessed genes, the mRNA levels of inhibin beta A (INHBA) and secreted phosphoprotein 1 (SPP1) were most consistently highly expressed in tumor tissues by 15.4- and 15.6-fold, respectively, as compared with normal tissues (P < 0.001), with 91.3% sensitivity and 95.7% specificity (receiver operating characteristic [ROC] curve area = 0.974) for the former and 82.6% sensitivity and 87.0% specificity (ROC curve area = 0.924) for the latter. Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs (P = 0.470). In contrast, the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs (P < 0.001), with 80.0% sensitivity and 81.5% specificity (ROC curve area = 0.857), and was also able to successfully differentiate between more severe disease conditions, T3 and T4 (P = 0.003), M0 and M1 (P = 0.043) and different histological variants (intestinal type vs diffuse type, P = 0.019). CONCLUSIONS: Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.

5.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(7): 907-913, 2017 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-28736366

RESUMEN

OBJECTIVE: To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation. METHODS: PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The ß sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining. RESULTS: Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of ß-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion. CONCLUSION: Lactic acid inhibits SEVI fibril formation in vitro.

7.
J Transl Med ; 15(1): 37, 2017 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-28202073

RESUMEN

BACKGROUND: Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). METHODS: Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan-Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients. RESULTS: The results showed that the density of Mφs decreased in the intra-tumor region (IT) of HCC, but remarkably increased in the IT of GC, as compared with their non-tumor regions (NT). In HCC, most CD68+ Mφs were CD204+ and CD169+ cells in the NT region; however, there was a significant decrease in the percentage of CD169+ Mφ in the IT region. In contrast, CD68+ Mφs comprised a smaller percentage of CD204+ than the CD169+ subpopulation in the NT region, while more CD204+ but fewer CD169+ cells were present in the IT region of GC. The density of CD204+ Mφs correlated with poor prognosis in HCC, and CD169+ Mφs were associated with good survival in both HCC and GC. Moreover, the combination of low numbers of CD204+ and high numbers of CD169+ Mφs was associated with improved OS in both GC and HCC. CONCLUSIONS: Mφs display tissue-specific distributions and distinct composition patterns in HCC and GC tissues. Our results suggested that different types of tumors might use diverse strategies to reconstitute Mφ patterns to promote tumor progression.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Macrófagos/patología , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Anciano , Antígenos CD/metabolismo , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Neoplasias Gástricas/patología , Análisis de Supervivencia , Adulto Joven
8.
Oncoimmunology ; 5(7): e1177690, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27622027

RESUMEN

PURPOSE: CD169 was first identified on macrophages (Mϕ) and linked to antigen presentation. Here, we showed CD169 expression on some CD8(+) T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169(+)CD8(+) T cells in tumor-draining LNs of colorectal cancer (CRC) patients. EXPERIMENTAL DESIGN: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169(+)CD8(+) T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiple-color immunofluorescence for CD169(+)CD8(+) T cell distribution and clinical values. The prognostic significance of CD169(+)CD8(+) T cells was evaluated by Kaplan-Meier analysis. RESULTS: A fraction of CD8(+) T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169(+)CD8(+) T cells to subcapsular sinus and interfollicular regions, closely associated with CD169(+) Mϕ. CD169(+)CD8(+) T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169(+)CD8(+) T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-α, and IFNγ levels, and promoted tumor-killing efficiency ex vitro. Moreover, CD169(+)CD8(+) T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival. CONCLUSIONS: We identified novel activated/cytolytic CD169(+)CD8(+) T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.

9.
J Pathol ; 239(2): 231-41, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27174787

RESUMEN

Macrophages are a major component of most solid tumours and can exert both anti- and pro-tumourigenic functions. Although the immunosuppressive/pro-tumour roles of macrophages have been widely examined, significantly less is known about macrophage subpopulations that have potential anti-tumour properties in humans. In the present study, a population of CD169(+) macrophages with relatively high expression levels of HLA-DR and CD86 was identified in human hepatocellular carcinoma tissues. The frequency of CD169-expressing macrophages within cancer nests was significantly lower than that found in paired non-tumour areas. In vitro experiments revealed that in the presence of anti-CD3 stimulation, CD169(+) macrophages could significantly enhance the proliferation, cytotoxicity, and cytokine production capacity of CD8(+) T cells in a CD169 molecule-dependent manner. Autocrine TGF-ß produced by tumour-stimulated macrophages was involved in the down-regulation of CD169 expression on these cells. Moreover, the accumulation of CD169(+) macrophages in tumour tissues was negatively associated with disease progression and predicted favourable survival in hepatocellular carcinoma patients, which was in contrast to the trend observed for total CD68(+) macrophages. Therefore, CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/inmunología , Macrófagos/inmunología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-2/inmunología , Antígeno B7-2/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Carcinoma Hepatocelular/patología , Regulación hacia Abajo , Femenino , Antígenos HLA-DR/inmunología , Antígenos HLA-DR/metabolismo , Humanos , Neoplasias Hepáticas/patología , Activación de Linfocitos , Macrófagos/patología , Masculino , Persona de Mediana Edad , Lectina 1 Similar a Ig de Unión al Ácido Siálico/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Microambiente Tumoral , Adulto Joven
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(3): 626-30, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26117868

RESUMEN

Refined TiCl4 is the key procedure in producing titanium sponge. Besides, the content of carbon and oxygen (C and O) impurities in titanium sponge and that of C and O impurities in refined TiCl4 presents the 4-times enrichment relationship. Therefore, the content control of the C and O impurities in refined TiCl4 becomes the key part for the quality control of titanium material. In order to control the oxygen and carbon, there is the need to analyze the source of C and O impurities so that strict control can be conducted over the impurities of refined TiCl4. Determination of CO2 in refined TiCl4 was significant for analysis of its impurities. CO2 could be determined by infrared spectroscopy due to its infrared characteristic spectrum line. However, normal infrared absorption cell was not fit for the sample analysis, because TiCl4 easily reacted with moisture in the air and immediately was hydrolyzed to form highly corrosive hydrochloric acid smoke. According to Lambert-Beer Law, which means the concentration (c(ξ)) and absorbance(A) - length (L) curve's slope have direct ratio. The infrared absorption cell with the window film of ZnSe (φ10 mm x 1 mm, wavenumers: 7 800 -440 cm(-1)) and the glass cell (optical path: 42, 22, 12, 7 and 4 mm) was assembled and utilized in determination of the CO2 in refined TiCl4 by standard addition method. The detection limit of CO2 was 0.92 mg x kg(-1), the regression equation was Y = 0.031 1X, R = 0.997 2; With standard addition method, the regression equation of CO2 was Y = 0.131 7X, R = 0.998 6, it's good in linearity relation, the CO2 content in refined TiCl4 is determined to be 1.53 mg x kg(-1) and SD up to 0.04 x mg x kg(-1). RSD of the method precision is between 0.53%-1.27%, while recovery rate is between 89.2%-96.8%. This infrared absorption device was safe, simple and convenient, easily removable and washable, and re-useable. The method could conduct the quantitative analysis over the CO2 content in refined TiCl4 through adding standard sample for one time, it could meet the requirement of determination of CO2 in refined TiCl4.

11.
J Pathol ; 237(3): 319-29, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26108200

RESUMEN

Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma (HCC). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumours strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumour-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor (HGF), c-Met increased the motility and matrix metalloproteinase (MMP) 9-producing capacity of tumour-associated monocytes. The intensity of c-Met expression on tumour-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/enzimología , Neoplasias Hepáticas/enzimología , Macrófagos/enzimología , Metaloproteinasa 9 de la Matriz/metabolismo , Monocitos/enzimología , Proteínas Proto-Oncogénicas c-met/metabolismo , Células del Estroma/enzimología , Animales , Comunicación Autocrina , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Movimiento Celular , Técnicas de Cocultivo , Femenino , Antígenos HLA-DR/metabolismo , Células Hep G2 , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Activación de Macrófagos , Macrófagos/patología , Masculino , Ratones Desnudos , Persona de Mediana Edad , Monocitos/patología , FN-kappa B/metabolismo , Pronóstico , Transducción de Señal , Células del Estroma/patología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(12): 3427-30, 2015 Dec.
Artículo en Chino | MEDLINE | ID: mdl-26964223

RESUMEN

The content control of the impurities in refined TiCl4 becomes the key part for the quality control of titanium material. Refined TiCl4 is the key procedure in producing titanium sponge. Besides, the content of the impurities in titanium sponge and that of the impurities in refined TiCl4 presents the 4-times enrichment relationship. Therefore, control the content of the oxygen, there is the need to analyze the source of oxygen impurities so that strict control can be conducted over the impurities of refined TiCl4. Determination of TiOCl2 in refined TiCl4 was significant for analysis of its impurities. TiOCl2 could be determined by infrared spectroscopy due to its infrared characteristic spectrum line. However, normal infrared absorption cell was not fit for the sample analysis, because TiCl4 easily reacted with moisture in the air and immediately was hydrolyzed to form highly corrosive hydrochloric acid smoke. According to Lambert-Beer Law, which means the concentration (c(x)) and absorbance (A)-length (L) curve's slope have direct ratio. The infrared absorption cell with the window film of ZnSe (Φ10 x 1 mm, wavenumers: 7800-440 cm⁻¹) and the glass cell (optical path: 22, 12, 7 and 4 mm) was assembled and utilized in determination of the TiOCl2 in refined TiCl4 by standard addition method. The detection limit of TiOCl2 was 17.8 mg · kg⁻¹, the regression equation was Y = 1.011 8X, R = 0.9963; With standard addition method, the regression equation of TiOCl2 was Y = 1.940 0X, R = 0.997 0, it' s good in linearity relation, the TiOCl2 content in refined TiCl4 is determined to be 833.8 mg · kg⁻¹ and SD up to 40.0 mg · kg⁻¹. RSD of the method precision is between 0.95%-1.94%, while recovery rate is between 88.5%-93.1%. This infrared absorption device was safe, simple and convenient, easily removable and washable, and re-useable. The method could conduct the quantitative analysis over the TiOCl2 content in refined TiCl4 through adding standard sample for one time, it could meet the requirement of determination of TiOCl2 in refined TiCl4.

13.
PLoS One ; 8(1): e50175, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23365634

RESUMEN

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Camptotecina/análogos & derivados , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genisteína/farmacología , Transducción de Señal/efectos de los fármacos , Inhibidores de Topoisomerasa I/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada , Camptotecina/farmacología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Ratones , Ratones Desnudos , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
PLoS One ; 7(11): e48062, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23144845

RESUMEN

It has been shown that vitamin D deficiency increases an individual's susceptibility to tuberculosis (TB). However, very little is known about the effect of vitamin D on the immune response to Mycobacterium tuberculosis (M. tb) in dendritic cells (DCs). Because DCs play an important role in TB infection, we investigated the phenotypic characteristics and functional capabilities of mouse bone marrow-derived dendritic cells (BMDCs) after stimulation with Bacillus Calmette-Guérin (BCG) in the presence or absence of 25(OH)D(3)(100 nM). Bone marrow cells from mice were cultured with GM-CSF (20 ng/ml) and were then treated with 25(OH)D(3) for 7 days. On day 6, 5 µg/ml of BCG (≥1.0×10(6) CFU/mg) was added to the cells for 24 hours, and on day 7, the non-adherent cells were harvested for phenotypic and functional analyses. After incubation with 25(OH)D(3), the expression levels of MHC-II and CD86 on the surface of the dendritic cells (DCs) and the ability of the DCs to stimulate proliferation of allogeneic mixed lymphocytes were lower than control cells (p<0.05). Furthermore, the level of Interleukin (IL) -4 secreted by the BMDCs in the 25(OH)D(3) culture was lower than that in the control culture (p<0.01). However, the BMDCs cultured with 25(OH)D(3) produced significantly higher levels of IL-2, IL-6, IL-10 and interferon gamma(IFN-γ) than those in the control culture (p<0.05). These findings suggest that 25(OH)D(3) modulates the immune response during mycobacterial infection by affecting the maturation and function of DCs.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Calcifediol/farmacología , Células Dendríticas/efectos de los fármacos , Mycobacterium bovis/fisiología , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Animales , Antígenos CD/metabolismo , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/microbiología , Células de la Médula Ósea/fisiología , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Citocinas/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/microbiología , Células Dendríticas/fisiología , Expresión Génica , Antígenos de Histocompatibilidad Clase II/metabolismo , Interacciones Huésped-Patógeno , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Linfocitos T/inmunología , Linfocitos T/fisiología
15.
J Shoulder Elbow Surg ; 21(9): 1207-12, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22047784

RESUMEN

BACKGROUND: Although the incidence of osteoarticular tuberculosis is increasing, glenohumeral joint tuberculosis is rare and often misdiagnosed in its early stages. Our objective was to study the incidence of the initial misdiagnosis as frozen shoulder and the duration of the prediagnostic period among patients with glenohumeral joint tuberculosis. METHODS: The clinical records of 21 patients with tuberculosis of the shoulder joint were retrospectively analyzed. RESULTS: Among the 16 patients with glenohumeral joint tuberculosis, 14 (87.5%) were initially diagnosed as having frozen shoulder instead of glenohumeral joint tuberculosis at their primary care clinics. Two patients actually showed both shoulder pain and limited range of motion, although they did not have a record of initial diagnosis with frozen shoulder. Consequently, 14 (87.5%) of the patients in our study with glenohumeral joint tuberculosis were likely misdiagnosed as having frozen shoulder. On the other hand, this group accounted for 3.6% (n = 16) of 450 patients who, during the same period, had been initially diagnosed with frozen shoulder at our institution. The mean prediagnostic period to attain the final, correct diagnosis of glenohumeral joint tuberculosis for this group was 14.5 months. CONCLUSION: It appears that misdiagnosis is common and early diagnosis of tubercular infection in the glenohumeral joint has become increasingly difficult. Glenohumeral joint tuberculosis should be suspected in cases of longstanding pain in the shoulder. It is necessary to re-examine these frozen shoulder patients with repeated plain radiographs followed by further imaging studies, especially magnetic resonance imaging, if conservative therapy fails.


Asunto(s)
Bursitis/diagnóstico , Articulación del Hombro , Tuberculosis Osteoarticular/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
16.
PLoS One ; 6(12): e28704, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22163326

RESUMEN

BACKGROUND: Recent studies have demonstrated that the coracohumeral ligament (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in CHL visualization between patients with frozen shoulder and normal volunteers using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the patients with a frozen shoulder. METHODS AND FINDINGS: There were 72 shoulder joints in 72 patients (50 femles and 22 males with a mean age of 53.5 years) with clinical evidence and MR imaging evidence of frozen shoulder. These were prospectively analyzed to identify and measure the maximum thickness of the CHL. The control group, which included 120 shoulder joints in 60 normal volunteer individuals (30 females and 30 males with a mean age of 50.5 years) was also referred for MR imaging. A chi-square test was used to analyze the data of the rate of CHL visualization between the patients with frozen shoulder and the control group. A two-way ANOVA was used to analyze the mean maximal thickness of CHL. The CHL was visualized in 110 out of 120 shoulders in the control group (91.7%), and in 57 out of 72 shoulders for the frozen shoulder group (79.2%), there was significant difference, using a chi-square test (P<0.05). The CHL was not visualized in 10 out of 120 shoulders in the control group (8.3%), and 15 out of 72 shoulders in the frozen shoulder group (20.8%), there was a significant difference (P<0.05). The CHL thickness (3.99±1.68 mm) in the patients with frozen shoulder was significantly greater than that thickness (3.08±1.32 mm) in the control group, using a two-way ANOVA (P<0.001). The CHL thickness (3.52±1.52 mm, n = 97) in the female shoulders was no significantly greater than that thickness (3.22±1.49 mm, n = 70) in the male shoulders, using a two-way ANOVA (P>0.05). CONCLUSIONS: MR Imaging is a satisfactory method for CHL depiction, and a thickened CHL is highly suggestive of frozen shoulder.


Asunto(s)
Bursitis/diagnóstico , Ligamentos Articulares/fisiopatología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Ligamentos Articulares/patología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Ortopedia/métodos , Hombro/patología , Articulación del Hombro/patología
17.
Hepatogastroenterology ; 58(110-111): 1687-93, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21940335

RESUMEN

BACKGROUND/AIMS: A high prevalence of serum IL-6 has been associated with the pathogenesis of hepatocellular carcinoma (HCC) in both animals and humans. However, it is not clear how the levels of serum IL-6 influence the prognosis of HCC patients. This study was carried out in order to attempt to answer this question. METHODOLOGY: A total of 156 adults were selected and categorized into four groups: healthy subjects (n=18), those with tumor recurrence (n=26), those initially diagnosed with HCC (n=32), and those with HCC (n=80) who received curative resection between 2002 and 2004 with five years of follow-up. Serum IL-6 levels were determined in all subjects by the same ELISA method. RESULTS: IL-6 was found in high levels in the serum of patients initially diagnosed with HCC (8.47±5.92, p<0.0001) and in patients with HCC and tumor recurrence (12±31.90, p=0.001) compared with healthy subjects (0.89±1.51). This includes all patients who received therapy between 2007 and 2008. The levels of serum IL-6 were positively correlated with tumor size (p=0.002) in the HCC patients who received curative resection between 2002 and 2004 with five years of follow-up. CONCLUSIONS: High levels of serum IL-6 correlated positively with tumor size and with poor prognosis in HCC patients.


Asunto(s)
Carcinoma Hepatocelular/sangre , Interleucina-6/sangre , Neoplasias Hepáticas/sangre , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/cirugía , Distribución de Chi-Cuadrado , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Pronóstico , Modelos de Riesgos Proporcionales
18.
J Vasc Interv Radiol ; 22(5): 702-9, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21514523

RESUMEN

PURPOSE: To evaluate whether the neutrophil-to-lymphocyte ratio (NLR) predicts survival in patients with unresectable hepatocellular carcinoma (HCC) before and after transarterial chemoembolization treatment. MATERIALS AND METHODS: Clinical and laboratory data for 145 consecutive patients undergoing transarterial chemoembolization for unresectable HCC during 2001-2004 were analyzed retrospectively. The NLR was recorded before and 3 days after treatment. RESULTS: The pretreatment mean NLR was 3.3; 59 (40.7%) patients had an elevated NLR (≥ 3.3). The median survival of patients with a high NLR was 8 months (range 1-28 months) compared with 12 months (range 2-41 months) for patients with a normal NLR; a significant difference was found in overall survival (log-rank test, P = .001). The NLR was increased in 127 (87.6%) patients after transarterial chemoembolization and was decreased in 18 patients; the increase indicated better outcomes (log-rank test, P = .006). Age (≥ 49 y), high NLR, decreased NLR after treatment, large tumor (≥ 5 cm), vascular invasion, and elevated serum α-fetoprotein (AFP) level all were predictors of poor survival. Multivariate analysis showed that a high NLR (P = .041) and vascular invasion (P = .040) were independent factors for predicting worse survival. CONCLUSIONS: A high NLR independently predicts poor survival in patients with unresectable HCC undergoing transarterial chemoembolization treatment, and an increased NLR indicates a better outcome than a decreased NLR for patients after transarterial chemoembolization.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Linfocitos/inmunología , Neutrófilos/inmunología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/mortalidad , Distribución de Chi-Cuadrado , China , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(1): 43-6, 2011 Jan.
Artículo en Chino | MEDLINE | ID: mdl-21428052

RESUMEN

Sr2 SiO4 : Eu2+ , Nd3+ was synthesized by solid state synthesis method, and the sensitization of Nd3+ near-infrared luminescence by Eu2+ was investigated. The characteristic near-infrared luminescence of Nd2+ in Sr2 SiO4 matrix was greatly enhanced by co-doping of Eu2+. The mechanism of energy transfer from Eu2+ to Nd3+ was analyzed through investigation of fluorescence excitation and emission spectra, and fluorescence lifetime. Excited Eu2+ (II) transfers energy effectively to Nd3+ through non-radiative energy transfer process in Sr2SiO4, resulting in greatly enhanced near-infrared luminescence of Nd3+, while sensitization of Nd3+ by Eu2+ (I) was achieved by the way of Eu2+ (II).

20.
Radiology ; 259(1): 286-95, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21330557

RESUMEN

PURPOSE: To compare the survival outcomes between hepatic resection and transarterial lipiodol chemoembolization (TACE) used as the initial treatment in patients with large (≥5 cm), multiple, and resectable hepatocellular carcinomas. MATERIALS AND METHODS: This study had local ethical committee approval; all patients gave written informed consent. Between January 2004 and December 2006, 168 consecutive patients were prospectively studied. As an initial treatment, 85 patients underwent hepatic resection and 83 underwent TACE. Of the 29 of 83 patients in whom there was a good response to TACE, 13 underwent subsequent hepatic resection. The remaining 16 patients, who refused hepatic resection, underwent TACE and local ablation. Repeated TACE was performed in patients with stable disease or progressive disease after initial TACE. The differences in survival between groups and subgroups were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were performed to clarify the prognostic factors for survival. RESULTS: The 1-, 3-, and 5-year overall survival rates for the initial hepatic resection group and the initial TACE group were 70.6%, 35.3%, 23.9% and 67.2%, 26.0%, 18.9%, respectively (P = .26). Complication rates were significantly higher in the initial hepatic resection group than in the initial TACE group (P < .01). The 1-, 3-, and 5-year overall survival rates in patients who underwent initial TACE and subsequent hepatic resection were 92.3%, 67.3%, and 50.5%, respectively, which were significantly higher than rates in patients treated with initial hepatic resection (P = .04) but were not significantly higher than in patients who responded well to TACE but refused hepatic resection (P = .07). Tumor size was the independent risk factor for survival. CONCLUSION: TACE might be a better initial treatment in patients with large, multiple, and resectable hepatocellular carcinomas; hepatic resection should be recommended to patients who respond well to TACE.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/estadística & datos numéricos , Aceite Etiodizado/administración & dosificación , Hepatectomía/estadística & datos numéricos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico , China/epidemiología , Femenino , Hemostáticos/administración & dosificación , Humanos , Inyecciones Intraarteriales , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA