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.
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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/metabolismoRESUMEN
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.
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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 JovenRESUMEN
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.
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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 JovenRESUMEN
Macrophages (MÏ) 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 MÏ 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/MÏ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.
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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/metabolismoRESUMEN
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.
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⻹) 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⻹, 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⻹ and SD up to 40.0 mg · kg⻹. 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.
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.
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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 SimpleRESUMEN
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.
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Bursitis/diagnóstico , Articulación del Hombro , Tuberculosis Osteoarticular/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
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.
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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 TratamientoRESUMEN
Radiofrequency ablation (RFA) has become an important treatment for hepatocellular carcinoma (HCC). The good candidates for RFA are patients with HCC at an early stage (solitary tumor ≤ 5 cm in diameter or ≤ 3 nodules ≤ 3 cm in diameter). Several clinical trials have shown that RFA is effective in resection for the treatment of small HCC. Until now, RFA has been widely used as a radical treatment for small HCC. RFA also plays an important role in the multidisciplinary treatment of HCC and is usually combined with other therapies such as resection, vascular intervention, intratumor ethanol injection, radiotherapy, chemotherapy, targeted drug therapy, and biological immune therapy. In this study, we will introduce our experience of RFA in the treatment of HCC in a cancer center in China.
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Carcinoma Hepatocelular/terapia , Ablación por Catéter/métodos , Neoplasias Hepáticas/terapia , China , Humanos , Recurrencia Local de Neoplasia , Tasa de SupervivenciaRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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 ProporcionalesRESUMEN
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).
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BACKGROUND AND OBJECTIVE: Single mode of radiofrequency ablation (RFA) often leads to limited ablation in the zone of necrosis. This study clarifies the efficacy of combining temperature- and power-controlled RFA for malignant liver tumors. METHODS: Between April 2008 and August 2008, 58 patients with malignant liver tumors received RFA at Sun Yat-sen University Cancer Center. The patients were divided into 2 groups using a random number table: one group received combined temperature- and power-controlled RFA (the combination group), and the other group received power-controlled RFA alone (the control group). RESULTS: Three patients were lost to follow-up and 55 patients were included for evaluation. Twenty-five patients with 29 tumors were treated by the combination RFA, and 27 tumors (93.1%) achieved either complete response (CR) or partial response (PR). One patient had a seriously decreased heart rate. In the control group, 30 patients with 32 tumors received power-controlled RFA, and 29 tumors (90.6%) achieved CR or PR. There were no serious complications. There was no difference between the combination and control groups in treatment time ((13.3 +/- 1.3) min vs. (10.2 +/- 2.3) min, P = 0.459). The number of sessions of RFA for the combination group was less than that of control group (1.3 sessions vs. 2.4 sessions), but the difference was not significant (P = 0.579). CONCLUSION: RFA controlling both temperature and power is effective and safe for patients with malignant liver tumors, and the number of sessions of RFA for the combination group was less than that of the control group.
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Ablación por Catéter/métodos , Neoplasias Hepáticas/terapia , Temperatura , Adulto , Anciano , Neoplasias del Colon/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Inducción de Remisión , alfa-Fetoproteínas/metabolismoRESUMEN
OBJECTIVE: To explore the efficacy and determine the risk factors of survival for recurrent hepatocellular carcinoma(HCC) treated by percutaneous radiofrequency ablation (PRFA). METHODS: From January 1999 to December 2008, 82 patients with recurrent HCC, with the diameter less than 7 cm for solitary tumor, or the largest tumor less than 5 cm for multiple tumors(the number of tumors less than 3), were treated by PRFA. The significance of 12 clinical or pathological variables in the risk factors of overall survival were assessed. RESULTS: The overall survival 1-, 3-, and 5-year survival rates were 75.8%, 43.9% and 34.5% (from the date of PRFA), and 95.1%, 63.2% and 46.6% (from initial hepatectomy), respectively. Univariate analysis indicated that tumor size before initial hepatectomy, recurrence interval from initial hepatectomy, number of recurrent tumors, diameter of largest recurrent tumor, serum glutamyl transpeptidase (GGT) and serum albumin (ALB) level were significant prognostic factors (P < 0.05, Kaplan-Meier Log-rank test). Multivariate analysis showed recurrence interval from initial hepatectomy, diameter of largest recurrence tumor, serum GGT and ALB level were significant prognostic (P < 0.05). CONCLUSION: PRFA is effective for recurrent HCC. Recurrence interval from initial hepatectomy, diameter of largest recurrent tumor, serum GGT and ALB level are significant prognostic factors.
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Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Neoplasias Hepáticas/cirugía , Adulto , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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.
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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 SupervivenciaRESUMEN
OBJECTIVE: To verify the accuracy of measurement of humeral head retroversion angle with multislice spiral computerized tomography (MSCT) volume rendering technique. METHODS: Twenty cadaveric humeri, 9 left and 11 right, free from traumatic or degenerative disfigurement, were harvested from embalmed cadavers. Before all soft tissues were removed by sharp dissection these humeri were scanned with 16 slice spiral CT scanner (CT1 group); then underwent anatomical measurement (anatomical measuring group); and at last, these humeri with marked anatomic neck were scanned with 16 slice spiral CT scanner again (CT2 group). The measurement was done by 2 orthopedists independently so as to diminish the measuring error. The differences in the humeral head retroversion angle between the CT1 group and anatomical measuring group, and the CT2 group and anatomical measuring group were analyzed with paired-samples T test. RESULTS: It showed that the results have no significant difference among them. The difference in the average value of humeral head retroversion angle between the CT1 group and anatomical measuring group was 1.64 degrees, and that between the CT2 group and anatomical measuring group was 0.65 degrees. CONCLUSION: Simple, fast, and precise, and suitable for clinical application, MSCT volume rendering technique can be used preoperatively, thus helping to realize the idea of individualization of shoulder arthroplasty and shoulder prosthesis. Although this technique is easy to be influence by the subjective factors of the observers, increase of experience and rational measurement may minimize the measurement error.
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Húmero/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Humanos , Húmero/anatomía & histología , Torsión MecánicaRESUMEN
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.
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BACKGROUND: Whether percutaneous radiofrequency ablation (PRFA) is as effective as repeat hepatectomy for recurrent small hepatocellular carcinoma (HCC) in the long-term remains unknown. METHODS: We included 110 patients into this study. Each patient had fewer than three recurrent HCCs, with the largest tumor less than 5 cm in diameter. Sixty-six patients with 88 tumors were treated by PRFA and 44 patients with 55 tumors were treated by repeat hepatectomy. RESULTS: The 1-, 2-, 3-, 4-, and 5-year overall survival rates after repeat hepatectomy and PRFA were 78.6%, 56.8%, 44.5%, 30.7%, and 27.6%, and 76.6%, 48.6%, 48.6%, 39.9%, and 39.9%, respectively (P = 0.79). The 1-, 2-, 3-, 4-, and 5-year overall survival rates after the initial hepatectomy for the two groups were 95.4%, 79.1%, 65.0%, 50.4%, and 42.9%, and 98.5%, 85.0%, 70.8%, 58.7%, and 55.6%, respectively, (P = 0.18). Subgroup analyses showed that there was no significant difference between the overall survivals of the two groups of patients when the interval of tumor recurrence from the initial hepatectomy was
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Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Hepatectomía , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Ultrasonografía Intervencional , Adulto JovenRESUMEN
AIMS: This study aimed to determine the risk factors of survival in patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (PRFA). PATIENTS AND METHODS: Between August 1999 and May 2005, 281 patients (250 males and 31 females) who were 33-80 years old (mean 65.3 years) received PRFA only or PRFA in combination with percutaneous ethanol injection (PEI) in our center. Patients were treated with PRFA or PEI by a percutaneous approach with ultrasound (US) guidance and were evaluated at regular intervals to determine disease recurrence and survival. The survival curves were constructed by the Kaplan-Meier method and compared by the log-rank test. The relative significance of the variables in the risk factors of overall survival was assessed by multivariate Cox proportional hazards regression analysis. RESULTS: At the end of the study, 189 patients were alive, and 92 were dead. Median survival was 48.7 months. The overall 1-, 3-, and 5-year survival rates were 89%, 54%, and 43%, respectively. The overall 1-, 3-, and 5-year survival rates for small tumor (size < or = 3cm) were 97.8%, 65.7%, 58.6%, respectively, for medium tumor (size 3.1-5cm) 94.1%, 57.1%, 37.1%, respectively, and for large tumor (size >5cm) 62.8%, 40.3%, 0%, respectively. Survival of patients treated with PRFA was dependent on tumor size (p<0.001; risk ratio [RR] 9.6, 95% CI 5.2-17.8), number of tumors (p=0.003; RR 1.6, 95% CI 1.2-2.0), combination with PEI (p=0.01; RR 0.6, 95% CI 0.4-0.9), Child-Pugh class (p=0.002; RR 2.0, 95% CI 1.3-3.0) and safety margin (p=0.0026; RR 0.6, 95% CI 0.4-0.9). CONCLUSIONS: PRFA is an effective treatment for HCC. This study showed after PRFA, tumor size, number of tumors, combination with PEI, safety margin, and Child-Pugh class were independent risk factors of survival.