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BACKGROUND: Many studies have sought associations between the total peripheral blood lymphocyte count and prostate cancer (PCa) prognosis, but not peripheral lymphocyte subsets. We explored the associations between the absolute counts of peripheral lymphocyte subsets and PCa patient survival. METHODS: 135 PCa patients were included in this study. The log-rank test and Kaplan-Meier method were employed to compare overall survival (OS) and progression-free survival (PFS) rates. Univariate and multivariate Cox's regression analyses were employed to identify prognostic factors. Flow cytometry analysis was used to determine the numbers of peripheral lymphocyte subsets. RESULTS: PCa patients with lower absolute counts of certain lymphocyte subsets showed poorer PFS and OS than those with higher absolute counts of these cells. The numbers of CD4+ T cells, CD3+ T cells, and natural killer (NK) cells were significantly higher in PCa patients of tumor node metastasis (TNM) â -â ¡ stages than those of TNM â III-IV stages. Univariate and multivariate Cox's regression analyses of OS and PFS indicated that neutrophil numbers > 4.81*109/L, CD4+ T cells ≤ 254 /µL, and NK cells ≤ 136 /µL were unfavorably prognostic for patients with PCa. CONCLUSIONS: Lower absolute counts of certain peripheral lymphocyte subsets (NK cells ≤ 136/µL and CD4+ T cells ≤ 254/µL) are prognostically unfavorable for PCa patients.
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Neoplasias de la Próstata , Subgrupos de Linfocitos T , Masculino , Humanos , Subgrupos Linfocitarios , Recuento de Linfocitos , PronósticoRESUMEN
Cytotoxic T cell antigen-4 (CTLA-4) is reportedly involved in the development of bladder cancer (BC). This research was designed to address the potential link between the +49A/G polymorphism in CTLA-4 gene and BC susceptibility. In total, 355 BC cases and 435 match controls from Chinese Han individuals were included eventually. The PCR-RFLR method was utilized to screen for this polymorphism. The +49A/G polymorphism was shown to increase the risk of BC. Subgroup analyses showed that this polymorphism was linked to an increased susceptibility to BC among individuals aged < 60 years, smokers and drinkers. Additionally, this polymorphism significantly correlated with tumor node metastasis and tumor size (≥3 cm). To sum up, this study reveals that the CTLA-4 +49A/G polymorphism could increase the risk of BC in Chinese Han people. Further large cohort studies with enough sample sizes are urgently warranted to verify the findings of this present study.
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Pueblo Asiatico/genética , Antígeno CTLA-4/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/genética , Factores de Edad , Anciano , Estudios de Casos y Controles , China/etnología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
BACKGROUND: Mounting evidence has demonstrated that circular RNAs (circRNAs) play indispensable roles in the progression of bladder cancer. Public database mining showed that hsa_circRNA_100146 (circRNA_100146) was highly expressed in bladder cancer. This study aimed to characterize the biological role of circRNA_100146 and clarify the underlying mechanism in bladder cancer. METHODS: We evaluated the relationship between circRNA_100146 expression and clinicopathological features. Furthermore, gain- and loss-of-function studies were conducted in bladder cancer cells via transfection with gene-carrying plasmids (over-expression) or specific short hairpin RNAs (knockdown). Moreover, computational algorithms and dual-luciferase reporter assays were performed to explore the possible mechanisms of action. Additionally, in vivo xenograft experiments were performed to further analyze the effect of circRNA_100146 on tumor growth. RESULTS: Our data showed that circRNA_100146 expression was increased in bladder cancer tissues and cell lines, and that high expression of circRNA_100146 was correlated with poor patient prognosis. Upregulation of circRNA_100146 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, whereas knockdown of circRNA_100146 displayed opposite effects on bladder cancer cells. Notably, circRNA_100146 could combine with miR-149-5p and promote ring finger protein 2 (RNF2) expression, thereby facilitating the progression of bladder cancer. Furthermore, overexpression of RNF2 reversed the effects of circRNA_100146 knockdown on the biological behaviors of bladder cancer cells. The in vivo experiments revealed that downregulation of circRNA_100146 dramatically delayed tumor growth. CONCLUSION: Our findings indicate that circRNA_100146 functions as a sponge of miR-149-5p in promoting bladder cancer progression by regulating RNF2 expression and that circRNA_100146 may serve as a novel biomarker in human bladder cancer.
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In this study, we aim at investigating the expression and regulation role of long non-coding RNA (lncRNA) DLX6-AS1 in bladder cancer (BC). DLX6-AS1 was highly expressed in BC tissues and significant negative correlation with the 5-year survival in the BC patients. The results showed that the proliferation, migration and invasion activities of BC cells were promoted by DLX6-AS1 overexpression, while cell apoptosis was repressed. However, knockdown DLX6-AS1 presented an pposite regulatory effect, and DLX6-AS1 knockdown delayed tumor in vivo. The potential target of DLX6-AS1 in BC was predicted and verified by RIP, RNA pull-down, and dual-luciferase reporter assays as miR-195-5p. The results showed that miR-195-5p was down-regulated in BC tissues, the expression of which was significantly negative correlated with DLX6-AS1 expression. In addition, the results also showed that miR-195-5p targeted and down-regulated the VEGFA. Knockdown of DLX6-AS1 up-regulated miR-195-5p expression and down-regulated VEGFA expression. Moreover, down-regulation of VEGFA expression caused by DLX6-AS1 inhibited phosphorylation of Raf-1, MEK1/2, and ERK1/2, while miR-195-5p inhibitors abolished the effect of silencing DLX6-AS1 expression. Our study demonstrated that DLX6-AS1 played an oncogenic role in BC through miR-195-5p-mediated VEGFA/Ras/Raf/MEK/ERK pathway.
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MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , MicroARNs/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Invasividad Neoplásica , Fosforilación , Proteínas Proto-Oncogénicas c-raf/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , Carga Tumoral , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas ras/metabolismoRESUMEN
BACKGROUND: A host of studies show Leptin (LEP) G19A polymorphism is correlated with the risk of various cancers, but the connection of this polymorphism with bladder cancer (BC) risk has not been reported. MATERIALS AND METHODS: This association was in explored in a case-control study involving 355 BC cases and 435 controls (all Chinese Han). Polymerase chain reaction-restriction fragment length polymorphism was conducted to genotype LEP G19A polymorphism. Analyses of allele and genotype distribution were evaluated using chi-square test. Continuous data were assessed by an independent samples t test or one-way ANOVA test. Odds ratio (OR) and 95% confidence interval (CI) were determined by logistic regression. RESULTS: LEP G19A polymorphism was significantly associated with a lower risk of BC (AA vs GG: adjusted OR, 0.40, 95% CI, 0.20-0.83, P = .013; AA + GA vs GG: adjusted OR, 0.70, 95% CI, 0.52-0.93, P = .015; AA vs GA + GG: adjusted OR, 0.45, 95% CI, 0.22-0.91, P = .026). In addition, A allele was associated with decreased risk for BC (A vs G: OR, 0.70, 95% CI, 0.55-0.89, P = .003). Stratified analyses by females, non-drinkers, and non-smokers all returned considerable relations. Furthermore, LEP G19A polymorphism was correlated with tumor size, tumor node metastasis, and distant metastasis in BC patients. CONCLUSIONS: LEP G19A polymorphism is associated with a less risk of BC.
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Predisposición Genética a la Enfermedad/genética , Leptina/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
BACKGROUND: Particulate matter (PM) exposure is closely associated with male infertility. Even though an association between poor semen quality and PM exposure has been widely accepted, which and when the semen parameter could be affected are still controversial. The purpose of this study is to estimate the effects of PM exposure on semen quality in Huai'an, China. OBJECTIVES AND METHODS: The study included 1955 men with 2073 semen samples between 2015 and 2017 with moderate to high exposure to air pollution in Huai'an, China. Three multivariable linear regression models were used to conduct exposure-response analyses for PM exposure and semen quality and to estimate the influence during different exposure periods by every 15 days period before ejaculation in all participants group and normal semen quality participants group. RESULTS: The average age of the observations was 28.9 ± 5.4 old years and the average abstinence period was 4.2 ± 1.5 days. The results showed high correlations between both PM2.5 and PM10 exposures throughout entire spermatogenesis and the declines of sperm count (ß: -0.93, p < 2 × 10-16 and ß: -1.00, p < 2 × 10-16), and sperm concentration (ß: -1.00, p < 2 × 10-16 and ß: -1.06, p < 2 × 10-16), and PM10 exposure decreased sperm total motility (ß: -0.60, p = 2.56 × 10-7), but not sperm progressive motility. Furthermore, PM2.5 exposure decreased sperm count and concentration during 15-75 lag days, and PM10 exposure showed significant association with sperm count and concentration during 0-75 lag days. PM2.5 and PM10 exposures during 45-59 lag days were both inversely associated with sperm total motility (all p value < 0.05). CONCLUSION: The present study revealed that ambient PM exposure throughout spermatogenesis during a long period, especially at early and middle stage were adversely associated with semen quality, sperm count and sperm concentration in particular.
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Contaminantes Atmosféricos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/toxicidad , Semen/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Adulto , Contaminantes Atmosféricos/análisis , China , Estudios de Cohortes , Exposición a Riesgos Ambientales/análisis , Humanos , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/patología , Modelos Lineales , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Material Particulado/análisis , Estudios Retrospectivos , Análisis de Semen , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Adulto JovenRESUMEN
The circulating matrix metalloproteinase-7 (MMP-7) levels are associated with the risk of bladder cancer (BC). MMP-7 gene -181A/G polymorphism may influence the expression of MMP-7 by affecting the transcriptional activity. A case-control study comprising 355 BC patients and 435 age- and gender-matched healthy controls was conducted in a Chinese Han population. The genotype of MMP-7 gene -181A/G polymorphism was determined by using polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that MMP-7 gene -181A/G polymorphism increased the risk of BC under the homozygous and allelic models. However, no association between MMP-7 gene -181A/G polymorphism and BC risk was obtained after adjusting for age, gender, smoking habits and drinking habits. Subgroup analyses showed MMP-7 gene -181A/G polymorphism was associated with increased risk for BC among the smokers and drinkers. Furthermore, AG or GG genotype of -181A/G polymorphism was associated with larger tumor size and lymphatic metastasis in BC patients. To sum up, MMP-7 gene -181A/G polymorphism is not associated with the susceptibility to BC. However, subgroup analyses obtain significant association among the groups of smokers and drinkers. Larger studies in other ethnic groups are needed to ascertain the contribution of MMP-7 gene -181A/G polymorphism to BC risk.
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Predisposición Genética a la Enfermedad , Genotipo , Metaloproteinasa 7 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/genética , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , China , Femenino , Técnicas de Genotipaje , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Medición de RiesgoRESUMEN
Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultraperformance liquid chromatography QExactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre and postgemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pregemcitabine BCa tissues differed significantly from those of pregemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pregemcitabine normal and postgemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesisfree tissuebased metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.
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Biomarcadores de Tumor/metabolismo , Desoxicitidina/análogos & derivados , Metaboloma/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/metabolismo , Desoxicitidina/uso terapéutico , Femenino , Humanos , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Metabolómica/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Análisis de Componente Principal/métodos , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismo , GemcitabinaRESUMEN
PURPOSE: We compared the accuracy of magnetic resonance (MR) urethrography and X-ray urethrography with operative findings for urethral strictures and observed their effects on treatment. MATERIALS AND METHODS: A total of 87 male patients (10-85 years of age) treated from January 2015 to December 2016 were included in the study. X-ray and MR urethrograms were performed for all patients to determine the location, length, and degree of urethral strictures and the organizational structure around the urethra, and the results were compared with the operative findings. One-way analysis of variance (ANOVA) was performed to compare the lengths of the urethral strictures determined by the two methods with the operative findings. A value of P < 0.05, calculated using GraphPad software, indicated statistical significance. RESULTS: Urethral stricture was more clearly shown on MR urethrography than on X-ray urethrography. The stricture length measured by conventional X-ray urethrography [(2.17 ± 0.65) cm] was much longer than that measured by MR urethrography [(1.68 ± 0.67) cm]. The surgical findings [(1.66 ± 0.70) cm] were significantly different from X-ray urethrography findings (F = 24.660, P = 0.000), but no significant difference was observed between the surgical findings and the stricture length measured by MR urethrography (F = 0.040, P = 0.842). CONCLUSION: Urethral strictures can be displayed more clearly and accurately by MR urethrography than by X-ray urethrography. MR urethrography is expected to become a necessary and standard procedure for the preoperative examination of urethral strictures.
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Imagen por Resonancia Magnética/métodos , Radiografía/métodos , Estrechez Uretral/diagnóstico , Procedimientos Quirúrgicos Urológicos/métodos , Adulto , Anciano de 80 o más Años , Niño , China , Precisión de la Medición Dimensional , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Reproducibilidad de los Resultados , Estrechez Uretral/cirugía , Urografía/métodosRESUMEN
Functional near-infrared spectroscopy (fNIRS) is an emerging non-invasive functional brain imaging technique, through detecting the changes of hemoglobin concentrations to investigate brain activities in various tasks. The aim of this study is to investigate the complexity of near-infrared spectroscopy signals during resting state and upper limb movements. Experimental study was designed by applying NIRS to collect the data especially for both healthy subjects and traumatic brain injury (TBI) patients. The modified multiscale entropy (MMSE) algorithm was employed to assess the complexity of fNIRS signals which may reflect the changes of brain activity when people underwent brain injury. The results that the mean MMSE of oxyhemoglobin values was lower in TBI patients compared to healthy subjects, indicated that MMSE was feasible to measure complexity of cerebral near-infrared spectroscopy signals in TBI patients, and that brain injury was associated with the decreased complexity of cerebrovascular reactivity. Moreover, measurement of complexity of brain signals has potential to provide significant guidance for rehabilitation.
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Lesiones Traumáticas del Encéfalo , Encéfalo , Entropía , Humanos , Espectroscopía Infrarroja CortaRESUMEN
OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = ï¼0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.
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Inhibinas/sangre , Varicocele/sangre , Adolescente , Anticuerpos/sangre , Biomarcadores/sangre , Niño , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Masculino , Espermatozoides/inmunología , Testosterona/sangreRESUMEN
microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages. We further demonstrated that insulin-like growth factor-1 receptor (IGF-1R) is a functional target of miR-143. Their expression levels were inversely correlated in bladder cancer samples. Overexpression of miR-143 inhibited cell proliferation and promoted chemosensitivity of bladder cancer 5637 cells to gemcitabine. Consistently, small interfering RNA-mediated knockdown of IGF-1R phenocopied miR-143 overexpression. Notably, the expression of IGF-1R is a predictor of patient prognosis. Collectively, our findings indicate that miR-143 is a valuable biomarker for bladder cancer. The miR-143/IGF-1R axis is associated with bladder cancer drug resistance and patient survival.
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Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV that produces interferon-ß (VSV-IFNß) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFNß against non-small cell lung cancer (NSCLC) is reported. NSCLC cell lines were treated in vitro with VSV expressing green fluorescence protein (VSV-GFP) and VSV-IFNß. VSV-GFP and VSV-IFNß were active against NSCLC cells. JAK/STAT inhibition with ruxolitinib re-sensitized resistant H838 cells to VSV-IFNß mediated oncolysis. Intratumoral injections of VSV-GFP and VSV-IFNß reduced tumor growth and weight in H2009 nude mouse xenografts (p < 0.01). A similar trend was observed in A549 xenografts. Syngeneic LM2 lung tumors grown in flanks of A/J mice were injected with VSV-IFNß intratumorally. Treatment of LM2 tumors with VSV-IFNß resulted in tumor regression, prolonged survival (p < 0.0001), and cure of 30% of mice. Intratumoral injection of VSV-IFNß resulted in decreased tumor-infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell expression of PDL-1 was increased after VSV-IFNß treatment. VSV-IFNß has potent antitumor effects and promotes systemic antitumor immunity. These data support further clinical investigation of VSV-IFNß for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Interferón beta/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos/inmunología , Virus de la Estomatitis Vesicular Indiana/fisiología , Animales , Carcinoma de Pulmón de Células no Pequeñas/virología , Modelos Animales de Enfermedad , Humanos , Interferón beta/biosíntesis , Interferón beta/genética , Neoplasias Pulmonares/virología , Ratones , Ratones Desnudos , Virus Oncolíticos/genética , Virus Oncolíticos/metabolismo , Virus de la Estomatitis Vesicular Indiana/genética , Virus de la Estomatitis Vesicular Indiana/inmunologíaRESUMEN
The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 µmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL.
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BACKGROUND: Ligamentum teres is hypertrophied and should be resected in developmental dysplasia of the hip (DDH). We have observed a relatively high prevalence of absence of ligamentum teres (ALT) in severe DDH. The purpose of this study was to determine: (1) the percentage of ALT in DDH; (2) the risk factors correlating with ALT; and (3) the pathologic characteristics of DDH with ALT. METHODS: In 2012, 123 patients were hospitalized for open reduction of DDH. Clinical records were retrospectively reviewed. The distribution of ALT was discerned. The risk factors correlating with ALT were analyzed. The pathologic changes of the DDH with ALT were observed. RESULTS: For the 123 patients, there were 14 males and 109 females with a mean age of 2.2±1.7 years old. Forty-one cases were diagnosed with bilateral DDH, and 27 of them had open reduction for both hips. Thus, 150 hips were included. According to the Tonnis grading, there were 1 grade I, 43 II, 67 III, and 39 IV patients. During operation, the ligamentum teres was confirmed absent in 24 patients (28 hips, 18.67%), 22 of the hips with ALT was Tonnis grade IV (78.57%). It was present in the other 99 patients (122 hips). The difference of ALT among different grade (χ2=43.959, P=0.000) and different age (χ2=10.748, P=0.008) showed statistical significance, respectively. Logistic regression revealed only grading was the correlation factor of ALT (P=0.000). Pathologically, the femoral head was extremely small. The cartilage surface showed erosion-like change. The acetabulum was also diminutive but could match the femoral head well. CONCLUSIONS: At our institution, 18.67% of DDH needing open reduction was combined with ALT. The degree of dislocation was the only correlation factor of ALT. If the Tonnis grade was high, the hip was often associated with ALT. CLINICAL RELEVANCE: This study defines the prevalence of ALT and its risk factor in DDH, which will help to better understand the imaging, pathologic findings, and clinical outcome of DDH.
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Luxación de la Cadera/cirugía , Osteotomía/métodos , Ligamentos Redondos/anomalías , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Oncolytic virus therapy is a promising therapy for numerous tumor types. Edmonston-strain measles virus (MV) has been tested in clinical trials for ovarian cancer, glioma, and myeloma. Therefore, the antitumor activity of MV against non-small-cell lung cancer (NSCLC) was assessed. METHODS: Human NSCLC cells and immortalized lung epithelial cell lines, Beas2B, were infected with either MV-producing green fluorescent protein or MV-producing carcinoembryonic antigen. Cells were assessed for viability, induction of apoptosis by caspase and poly-ADP ribose polymerase cleavage, and for viral transgene production. The dependency of MV entry on CD46 and nectin-4 were determined using blocking antibodies. The role of host translational activity on viral replication was assessed by overexpression of eIF4E and translation inhibition. Antitumor activity was assessed by measuring treated NSCLC xenografts from flanks of nude mice. RESULTS: MV infection of NSCLC cells results in potent cell killing in most of the cell lines compared with immortalized Beas2B cells and induces apoptosis. MV infection was prevented by blocking of CD46, however independent of nectin-4 blockade. Tumor weights are diminished after intratumoral injections of MV-producing carcinoembryonic antigen in one of two cell lines and result in detectable viral transgene in serum of mice. CONCLUSIONS: These data indicate that MV is oncolytic for human NSCLC and this was independent of nectin-4 expression. Dysregulated protein translational machinery may play a role in determining tumor tropism in NSCLC. MV combined with gemcitabine could be explored further as chemovirotherapy for NSCLC.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Virus del Sarampión/fisiología , Viroterapia Oncolítica , Carga Tumoral , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Antimetabolitos Antineoplásicos/farmacología , Antígeno Carcinoembrionario/efectos de los fármacos , Antígeno Carcinoembrionario/genética , Antígeno Carcinoembrionario/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Células Epiteliales/virología , Factor 4E Eucariótico de Iniciación/metabolismo , Proteínas Fluorescentes Verdes/genética , Humanos , Hidrazonas/farmacología , Pulmón , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Vacuna Antisarampión , Virus del Sarampión/genética , Proteína Cofactora de Membrana/antagonistas & inhibidores , Proteína Cofactora de Membrana/metabolismo , Ratones , Fosfoproteínas/metabolismo , Sirolimus/farmacología , Tiazoles/farmacología , Replicación Viral , GemcitabinaRESUMEN
BACKGROUND: This single-arm, phase II study was designed to determine the efficacy and safety of panobinostat and bortezomib in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients had to have a histological diagnosis of pancreatic cancer and progression on a standard gemcitabine-based therapy. Treatment cycles consisted of 21 days, with bortezomib given twice weekly at 1.3 mg/m(2) and panobinostat three times weekly at 20 mg during the first two weeks, followed by a 9-day rest period. RESULTS: Seven patients (3 female, 4 male) were treated with at least one cycle, but the study was suspended after the enrollment of these patients because of a complete lack of treatment responses and early treatment-related toxicity. Median progression-free survival was 2.1 months (95% Confidence interval: 1.7-2.3 months). The most common grade 3 or 4 adverse events were thrombocytopenia (57%) and diarrhea (29%). CONCLUSION: Treatment of advanced pancreatic cancer with bortezomib in combination with panobinostat is not supported by our clinical study.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Ácidos Borónicos/administración & dosificación , Bortezomib , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Ácidos Hidroxámicos/administración & dosificación , Indoles , Masculino , Persona de Mediana Edad , Panobinostat , Pirazinas/administración & dosificación , GemcitabinaRESUMEN
OBJECTIVE: To investigate human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes and clinical features in neonates with congenital infections. METHODS: Urine samples were obtained from 67 neonates with HCMV infection confirmed by polymerase chain reaction (PCR). The gB gene fragment was amplified by nested PCR. HCMV gB genotyping was detected by restriction fragment length polymorphism. RESULTS: In all these cases, the most prevalent genotype was gBl (50.7%), followed by gB3 (23.9%), gB2 (17.9%), and gBl/gB3 coinfection (7.5%); gB4 was not found. Moreover, gB1 was more prevalent in infants with liver damage (27/37, 73.0%) than in other symptomatic infants without liver damage (13/30, 43.3%; P < 0.05). CONCLUSION: The gBI genotype is the most prevalent in infants with congenital symptomatic HCMV disease, especially in those with liver damage, followed by genotypes gB3, gB2, and gB4.
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Infecciones por Citomegalovirus/virología , Citomegalovirus/genética , Enfermedades del Recién Nacido/virología , Proteínas del Envoltorio Viral/genética , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/orina , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Proteínas del Envoltorio Viral/orinaRESUMEN
OBJECTIVE: to discuss the feasibility and efficacy of one-stage anteroposterior hemi-vertebra resection and segmental internal fixation for young children with congenital scoliosis. METHODS: thirty-five patients undergoing one-stage anteroposterior hemi-vertebra resection and segmental internal fixation were retrospectively studied. The mean followed-up period was 5.3 years (range: 1.2 - 8.7). The Cobb's angle of scoliosis at pre and post-operation was compared. RESULTS: all children's parents were satisfied with the outcome. The Cobb's angle of scoliosis was corrected from (42.5 ± 6.7)° to (16.2 ± 3.2)° at post-operation. The coronal correction rate was 64.7%. The angle of kyphosis improved from preoperative (33.5 ± 5.2)° to postoperative (13.3 ± 5.6)° in 14 cases. Operative duration was 210 - 280 minutes with an average of 240 minutes. The intra-operative blood loss was 80 - 200 ml with an average of 120 ml. There was no significant correction loss at follow-up. No neurological complication, infection or pedicular fracture was reported. CONCLUSION: the procedure of one-stage anteroposterior hemi-vertebra resection and segmental internal fixation is a safe and effective treatment for scoliosis by congenital hemi-vertebra in young children. A satisfactory correction may be achieved with a short fusion segment.
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Fijación Interna de Fracturas/métodos , Escoliosis/cirugía , Columna Vertebral/cirugía , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Accumulating data have implicated the selenium-containing cytosolic glutathione peroxidase, GPx-1, as a determinant of cancer risk and a mediator of the chemopreventive properties of selenium. Genetic variants of GPx-1 have been shown to be associated with cancer risk for several types of malignancies. To investigate the relationship between GPx-1 enzyme activity and genotype, we measured GPx-1 enzyme activity and protein levels in human lymphocytes as a function of the presence of two common variations: a leucine/proline polymorphism at codon 198 and a variable number of alanine-repeat codons. Differences in GPx activity among these cell lines, as well as in the response to the low-level supplementation of the media with selenium, indicated that factors other than just genotype are significant in determining activity. To restrict the study to genotypic effects, human MCF-7 cells were engineered to exclusively express allelic variants representing a combination of either a codon 198 leucine or proline and either 5 or 7 alanine-repeat codons following transfection of GPx-1 expression constructs. Transfectants were selected and analyzed for GPx-1 enzyme activity and protein levels. GPx-1 with 5 alanines and a leucine at codon 198 showed a significantly higher induction when cells were incubated with selenium and showed a distinct pattern of thermal denaturation as compared with GPx-1 encoded by the other examined alleles. The collective data obtained using both lymphocytes and MCF-7 indicate that both intrinsic and extrinsic factors cooperate to ultimately determine the levels of this enzyme available to protect cells against DNA damage and mutagenesis.