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1.
Int J Mol Sci ; 17(11)2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27854304

RESUMO

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222-3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177-3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.


Assuntos
Plaquetas/patologia , Proteína C-Reativa/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidade , Neutrófilos/patologia , Albumina Sérica/metabolismo , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Carcinoma , Contagem de Células , Feminino , Escala de Resultado de Glasgow , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
2.
J Virol ; 88(12): 6660-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24696473

RESUMO

UNLABELLED: Epstein-Barr virus (EBV) infection has been observed in tumor-infiltrated macrophages, but its infection effects on macrophage immune functions are poorly understood. Here, we showed that some macrophages in the tumor stroma of nasopharyngeal carcinoma (NPC) tissue expressed the immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) more strongly than did tumor cells. EBV infection induced mRNA, protein, and enzymatic activity of IDO in human monocyte-derived macrophages (MDMs). Infection increased the production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), whereas the neutralizing antibodies against TNF-α and IL-6 inhibited IDO induction. EBV infection also activated the mitogen-activated protein kinase (MAPK) p38 and NF-κB, and the inhibition of these two pathways with SB202190 and SN50 almost abrogated TNF-α and IL-6 production and inhibited IDO production. Moreover, the activation of IDO in response to EBV infection of MDMs suppressed the proliferation of T cells and impaired the cytotoxic activity of CD8(+) T cells, whereas the inhibition of IDO activity with 1-methyl-l-tryptophan (1-MT) did not affect T cell proliferation and function. These findings indicate that EBV-induced IDO expression in MDMs is substantially mediated by IL-6- and TNF-α-dependent mechanisms via the p38/MAPK and NF-κB pathways, suggesting that a possible role of EBV-mediated IDO expression in tumor stroma of NPC may be to create a microenvironment of suppressed T cell immune responses. IMPORTANCE: CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the control of viral infections and destroy tumor cells. Activation of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in cancer tissues facilitates immune escape by the impairment of CTL functions. IDO expression was observed in some macrophages of the tumor stroma of nasopharyngeal carcinoma (NPC) tissue, and IDO could be induced in Epstein-Barr virus (EBV)-infected human monocyte-derived macrophages (MDMs). NPC cells and macrophages have been found to produce IDO in a gamma interferon (IFN-γ)-dependent manner. Instead, EBV-induced IDO expression in MDMs is substantially mediated by IL-6- and TNF-α-dependent mechanisms via the p38/MAPK and NF-κB pathways, which suppressed the proliferation of T cells and impaired the cytotoxic activity of CD8(+) T cells. This finding provides a new interpretation of the mechanism of immune escape of EBV and shows the immunosuppressive role of EBV-mediated IDO expression in tumor stroma of NPC.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Macrófagos/enzimologia , NF-kappa B/imunologia , Neoplasias Nasofaríngeas/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Adulto , Carcinoma , Células Cultivadas , Infecções por Vírus Epstein-Barr/enzimologia , Infecções por Vírus Epstein-Barr/genética , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interleucina-6/genética , Interleucina-6/imunologia , Sistema de Sinalização das MAP Quinases , Macrófagos/imunologia , Masculino , Monócitos/enzimologia , Monócitos/imunologia , NF-kappa B/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimologia , Neoplasias Nasofaríngeas/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
3.
BMC Complement Altern Med ; 15: 137, 2015 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-25925762

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population aged over 65 years old. Mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (DA) neurons in PD. Paeonolum, a main component isolated from Moutan cortex, has potent antioxidant ability. Here, we have examined the effects of paeonolum against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells. METHODS: The overall viability and neurodegeneration of DA neurons was assessed in ETvmat2:green fluorescent protein (GFP) transgenic zebrafish, in which most monoaminergic neurons are labeled by GFP. Damage to PC12 cells was measured using a cell viability assay and assessment of nuclear morphology. Intracellular reactive oxygen species (ROS) and the level of total GSH were assessed. The mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome C release and caspase-3 activity were also examined in PC12 cells. RESULTS: Paeonolum protected against MPP(+)-induced DA neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. Similar neuroprotection was replicated in the PC12 cellular model of MPP(+) toxicity. Paeonolum attenuated MPP(+)-induced intracellular ROS accumulation and restored the level of total GSH in PC12 cells. Furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by MPP(+). CONCLUSIONS: Collectively, the present study demonstrates that paeonolum protects zebrafish and PC12 cells against MPP(+)-induced neurotoxicity.


Assuntos
Antioxidantes/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Paeonia/química , Doença de Parkinson/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Citocromos c/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/prevenção & controle , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Doença de Parkinson/metabolismo , Extratos Vegetais/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra
4.
Sex Transm Dis ; 41(1): 29-34, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24326578

RESUMO

BACKGROUND: The widespread reverse syphilis screening algorithm involves 1 more treponemal test than the traditional screening algorithm, resulting in increased medical costs. In the first screening step of the algorithm, a chemiluminescence microparticle immunoassay is used to detect Treponema pallidum (TP) antibody on the basis of signal-to-cutoff (S/CO) ratios. We hypothesized that by analyzing S/CO ratios, we could determine a strategy to reduce unnecessary confirmatory testing. METHODS: The ARCHITECT Syphilis TP assay using the chemiluminescence microparticle immunoassay was used as a syphilis screening test, and all reactive results were followed up with a toluidine red unheated serum test (TRUST) and a TP particle agglutination (TPPA) assay. We evaluated the S/CO ratios of 319 reactive samples of a total of 8980 that were included in the screening tests. A receiver operating characteristic curve was used to determine the optimal S/CO ratio to predict confirmatory TPPA results. RESULTS: When the S/CO ratio was 9.9 or greater, the specificity and positive predictive value were both determined to be 100.0%. All samples (194/194) with S/CO ratios of 9.9 or greater, even with negative results for TRUST, were confirmed to be positive for treponemal antibody. CONCLUSIONS: A sample with an S/CO ratio of 9.9 or greater in initial screening does not need an extra confirmatory TPPA test, although the sample has a negative result for TRUST. We propose a potentially cost-effective reverse screening algorithm, obviating the need for the secondary treponemal testing in 65.2% of the screening-reactive samples.


Assuntos
Técnicas Imunoenzimáticas , Medições Luminescentes , Programas de Rastreamento/métodos , Sífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Algoritmos , Anticorpos Antibacterianos/isolamento & purificação , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Sífilis/imunologia , Treponema pallidum/imunologia
5.
BMC Cancer ; 12: 365, 2012 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-22917173

RESUMO

BACKGROUND: Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC). METHODS: SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann-Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox's proportional hazards model. RESULTS: SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls (13.88 ± 15.19 mg/L vs. 2.26 ± 1.66 mg/L, P < 0.001). Elevation of SAA levels (≥ 8.0 mg/L) was observed in 54.5% (91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001), histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of SAA (≥ 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001). CONCLUSIONS: An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Proteína Amiloide A Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estatísticas não Paramétricas , Análise de Sobrevida
6.
Cancer Chemother Pharmacol ; 90(3): 229-237, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35922567

RESUMO

PURPOSE: The time of a paclitaxel (PTX) concentration remains above 0.05 µM (Tc > 0.05) has been associated with PTX-induced adverse effects in Caucasians, while limited studies were reported in Asians. This study was aimed to explore the characteristics of Tc > 0.05 and the relationship between PTX exposure and toxicity in East-Asian patients. METHODS: This study was based on two prospective phase II clinical trials and patients with advanced nasopharyngeal cancer (NPC) and non-small cell lung cancer (NSCLC) who were naïve to PTX were included independently. Eligible patients receive PTX (175 mg/m2) and carboplatin (AUC = 5) treatment every 3 weeks. PTX pharmacokinetic analysis was accessed. The relationship between PTX exposure and toxicities after first cycle as well as clinical efficacy was evaluated. RESULTS: A total of 93 NPC and 40 NSCLC patients were enrolled. PTX exposure was consistent in two trials with average Tc > 0.05 duration of 38.8 h and 38.4 h, respectively. Average Tc > 0.05 in patients with grade 3/4 neutropenia was significantly higher than those without severe neutropenia in NPC patients (P = 0.003) and NSCLC patients (P = 0.007). Cut-off value of Tc > 0.05 were identified from the NPC cohort and then verified in the NSCLC cohort, dividing patients into high exposure Tc > 0.05 group (> 39 h) and low exposure group (≤ 39 h). Incidence of grade 3/4 neutropenia were significantly higher in the high exposure group in NPC cohort (43.3% vs 10.0%, P < 0.001) and NSCLC cohort (42.1% vs 9.5%, P = 0.028). No significant relationship between Tc > 0.05 and efficacy were observed. CONCLUSION: Patients with PTX Tc > 0.05 duration above 39 h experience more severe neutropenia than those under 39 h. Prospective studies are needed to verify this threshold.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Paclitaxel/uso terapêutico , Estudos Prospectivos
7.
Clin Dev Immunol ; 2011: 384726, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22013481

RESUMO

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8(+) tumour-infiltrating lymphocytes (CD8(+) TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8(+) TILs. Patients with high IDO expression and a low number of CD8(+) TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8(+) TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8(+) TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Progressão da Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Interferon gama/metabolismo , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Estadiamento de Neoplasias , Evasão Tumoral , Microambiente Tumoral/imunologia
8.
Ann Transl Med ; 8(5): 236, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309383

RESUMO

BACKGROUND: Area under time-concentration curve (AUC) of docetaxel is related with its toxicity and efficacy. The aim of this study is to investigate the target range of docetaxel AUC in Chinese head and neck cancer (HNC) patients. METHODS: Eligible HNC patients were enrolled and received at least 2 cycles of docetaxel-based chemotherapy. A simplified pharmacokinetic (PK) strategy (2 monitored samples) was developed to simulate docetaxel AUC using the nonlinear mixed-effect modelling program. Preliminary target range of AUC was pre-set as 2.5-3.7 µg·hr/mL according to pooled analysis from 8 previous studies. Fisher exact test was used to analyze the relationship between AUC with neutropenia and efficacy, and to verify the target range. RESULTS: Thirty-nine eligible patients were enrolled. Grade 3-4 and grade 4 neutropenia rate in 1st cycle was 64% and 36%, respectively. AUC simulation by simplified PK strategy was acceptable compared to full sampling method from the analysis of archived 300 patients' data, with -5.67% of mean prediction error (MPE). Median AUC of all patients was 2.58 µg·hr/mL (range from 1.28 to 9.39). A significant correlation (P=0.007) was detected between AUC and body surface area (BSA)-dosage, but BSA contributed only 18.3% of AUC inter-individual variability. Docetaxel AUC was significantly related with the severity (grade 3-4) of neutropenia (correlation of coefficient was 0.452, P=0.004). Fourteen patients (36%) were within the target AUC range. Patients with AUC above the target experienced more severe neutropenia (grade 3-4 rate 100% vs. 56%, P=0.036; grade 4 rate 86% vs. 25%, P=0.005). No significant difference of response rate was found between patients within the target or not. CONCLUSIONS: A simplified samples PK strategy was developed for docetaxel AUC simulation. The target range of docetaxel AUC in Chinese HNC patients was suggested at 2.5-3.7 µg·hr/mL for reduced toxicity without compromising efficacy of docetaxel treatment.

10.
Clin Pharmacokinet ; 55(10): 1205-1216, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27138786

RESUMO

BACKGROUND AND OBJECTIVE: 5-Fluorouracil plus cisplatin is the most commonly used chemotherapy regimen for nasopharyngeal carcinoma (NPC). The objective of this study was to establish an individualized 5-fluorouracil treatment model based on pharmacokinetic and pharmacodynamic analyses of 5-fluorouracil in East-Asian NPC patients. METHODS: A total of 122 NPC patients were administered 5-fluorouracil plus cisplatin treatment. Blood samples were collected to calculate the area under the concentration-time curve (AUC) for 5-fluorouracil, and expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) at both protein and messenger RNA (mRNA) levels were analyzed in the tumor tissues from 73 patients in the same cohort. RESULTS: The results showed a wide (sevenfold) pharmacokinetic variability of 5-fluorouracil exposure (measured as AUC) based on body surface area (BSA) dosing. Pharmacokinetic analyses revealed that the 5-fluorouracil AUC range had a significant impact on the response of patients to 5-fluorouracil and related toxicities. Patients with 5-fluorouracil AUC <25 mg·h/L responded unsatisfactorily to 5-fluorouracil (overall response rate [ORR] 17.5 % lower than patients with AUC 25-35, p = 0.176; and 26.1 % lower than patients with AUC >35, p = 0.031). On the other hand, patients with 5-fluorouracil AUC >35 mg·h/L experienced more 5-fluorouracil-related toxicities (a grade 3 or higher toxicity rate 57.1 % higher than patients with AUC 25-35, p < 0.001; and 60.0 % higher than AUC >35, p < 0.001). The established 5-fluorouracil therapeutic window in head and neck cancer (HNC) [AUC 25-35 mg·h/L) was verified in our study. Pharmacodynamic analyses indicated a positive correlation between TS and DPD expression (p < 0.001) and, despite the pharmacokinetic influences, low expression of TS mRNA in tumor tended to have a better ORR (81.0 vs. 54.3 %, p = 0.051). No significant association was found between DPD expression and ORR. CONCLUSIONS: The therapeutic window of 5-fluorouracil for East-Asian NPC patients was verified as 25-35 mg·h/L based on lower toxicity and higher efficacy. TS mRNA expression showed potentially predictive value in 5-fluorouracil treatment, and personalized treatment based on pharmacokinetics and pharmacodynamics proved to be clinically beneficial and is worthy of further clinical studies.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Fluoruracila/farmacocinética , Fluoruracila/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacologia , Área Sob a Curva , Povo Asiático , Cisplatino/administração & dosagem , Di-Hidrouracila Desidrogenase (NADP)/biossíntese , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Ásia Oriental , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , RNA Mensageiro/biossíntese , Timidilato Sintase/biossíntese
12.
Transl Oncol ; 8(6): 497-503, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26692531

RESUMO

Preoperative serum lactate dehydrogenase (LDH) has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC) treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ(2) test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor-lymph node-metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.

13.
PLoS One ; 9(3): e91080, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24625581

RESUMO

BACKGROUND: Although the alterations of lipid profile in lung cancer have been documented, the prognostic value of serum HDL-C level and its correlation with inflammation in NSCLC remain unknown. SUBJECTS AND METHODS: Levels of preoperative serum lipid concentrations (including HDL-C, LDL-C, TC, and TG) and the inflammatory biomarker C-reactive protein level (CRP) were retrospectively analyzed in 228 patients with NSCLC and in 300 healthy controls. The serum lipid levels in these two populations were compared. Univariate and multivariate cox hazards analyses were performed to investigate the prognostic value of serum lipid levels in NSCLC. The correlation between CRP and lipid profile were also analyzed. RESULTS: Compared with those in normal controls, the serum HDL-C, LDL-C, and TC levels were statistically decreased and the TG levels were significantly increased in 228 NSCLC patients. The patients with decreased levels of HDL-C had significantly lower 5-year survival rates than those with normal HDL-C, not only in the whole NSCLC cohort but also in the subgroups stratified according to the disease T, N classifications, and metastasis, whereas the other lipid components were not independent prognostic factors for NSCLC. Of the lipid components, a lower HDL-C level was observed more often in patients with a high CRP level than in those with a normal CRP level. Spearman's rank correlation analysis revealed that the HDL-C level presented a negative correlation with the CRP level (r = -0.360, p<0.001). CONCLUSIONS: A decreased level of preoperative HDL-C was found to be associated with poor survival in patients with NSCLC. Serum HDL-C level may be a clinical prognosis factor for NSCLC patients. In addition, a negative correlation was present between the levels of HDL-C and CRP, the well-known inflammation biomarker.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , HDL-Colesterol/sangue , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores ErbB/genética , Feminino , Humanos , Inflamação/sangue , Estimativa de Kaplan-Meier , Lipídeos/sangue , Lipídeos/química , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
14.
Int J Radiat Oncol Biol Phys ; 73(5): 1552-9, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19306752

RESUMO

PURPOSE: To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-beta1mRNA in rats. METHODS AND MATERIALS: A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-beta1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction. RESULTS: Compared with the irradiated group, levels of TGF-beta1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-beta1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1. CONCLUSION: PTX and Vit. E downregulated the expression of TGF-beta1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.


Assuntos
Coração/efeitos da radiação , Miocárdio/metabolismo , Pentoxifilina/uso terapêutico , Protetores contra Radiação/uso terapêutico , Tocoferóis/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Fibrose/metabolismo , Fibrose/patologia , Coração/efeitos dos fármacos , Cardiopatias , Masculino , Miocárdio/patologia , RNA Mensageiro/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Lesões por Radiação/prevenção & controle , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
15.
Ai Zheng ; 27(1): 18-24, 2008 Jan.
Artigo em Zh | MEDLINE | ID: mdl-18184458

RESUMO

BACKGROUND & OBJECTIVE: Radiation-induced heart damage is one of the prognostic factors of the patients who had received radiation to the mediastinum. This study was to investigate the correlation of transforming growth factor-beta1 (TGF-beta1) mRNA expression to the radiation response of the heart in rats, in order to provide references for further study on irradiation-induced heart damage. METHODS: Sixty Sprague-Dawley rats were divided into 2 groups: the 30 rats in irradiation group were irradiated with 20 Gy on the heart; the 30 rats in control group received no irradiation. At each time point of the 1st day, the 2nd, 4th, 8th 12th, and 24th week after irradiation, 5 rats in each group were killed. The serum levels of cardiac troponin and isoenzyme of creatine kinase (CK-MB) were detected. The expression of TGF-beta1 mRNA was detected by polymerase chain reaction (PCR). Heart damage was observed with Masson staining under microscope. RESULTS: The serum level of cardiac troponin was elevated at 24 h after irradiation, and reached the peak at 2 weeks after irradiation, which was significantly higher than that in control group [(0.73+/-0.11) ng/mL vs. (0.11+/-0.04) ng/mL, P<0.05]. There was no significant difference in the serum level of CK-MB between two groups (P>0.05). The expression of TGF-beta1 mRNA was elevated at the 1st day after irradiation, and reached peaks at 2 and 12 weeks after irradiation, which were significantly higher than those in control group [(8.55+/-1.19)x10(-8) microg/mL vs. (1.27+/-0.11)x10(-8) microg/mL, (4.63+/-0.41)x10(-8) microg/mL vs. (1.35+/-0.15)x10(-8) microg/mL, P<0.05]. The proportion of collagen fibers was increased since 2 weeks after irradiation, which was significantly higher than that in control group [(2.87+/-0.37)% vs. (1.14+/-0.55)%, P<0.05]. The expression of TGF-beta1 mRNA was positively correlated to the proportion of collagen fibers in the rat hearts after irradiation (r=0.48, P<0.05). CONCLUSIONS: TGF-beta1 is involved not only in the onset but also in the development of radiation fibrosis. Inhibiting the peak expression of TGF-beta1 mRNA may reduce the radiation-induced damage to the heart.


Assuntos
Cardiopatias/metabolismo , Coração/efeitos da radiação , Miocárdio/patologia , Lesões Experimentais por Radiação/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Creatina Quinase Forma MB/sangue , Fibrose/patologia , Cardiopatias/sangue , Cardiopatias/patologia , Masculino , Miocárdio/metabolismo , RNA Mensageiro/metabolismo , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Troponina/sangue
16.
Ai Zheng ; 21(11): 1251-3, 2002 Nov.
Artigo em Zh | MEDLINE | ID: mdl-12526228

RESUMO

BACKGROUND & OBJECTIVE: Tumor supplied group of factors (TSGF) is the first kind of tumor marker in vitro which was primarily obtained the approval by Chinese government to land the market, there was no any reports about it in abroad before. In order to know its specificity and sensitivity, we designed this study to detect the TSGF in serum of the patients with malignancies and evaluate its clinical significance for diagnosis. METHODS: Serum TSGF in 523 cases with malignancies and 400 cases of normal control were detected with chemical colorimetry. The diagnostic accuracy was evaluated. RESULTS: Mean levels of serum TSGF in the patients without malignancies (group A), the patients with malignancies (group B), the patients after curative treatment for malignancies (group C) and the normal control (group D) were 66.57, 71.24, 60.78, and 53.56 u/ml, respectively. After the statistical analysis, differences between the group A and group B, group A and group D, group B and group C, group B and group D, group C and group D were found (P < 0.05). But there was no obvious difference between the group A and group C (P > 0.05). The sensitivity was 63.86%; the specificity was 90.89%; the truly negative rate was 87.01%; and the falsely negative rate was 13.00%. CONCLUSIONS: Serum TSGF increased in malignancies and may be helpful for screening and early detection of cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias da Mama/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Sensibilidade e Especificidade
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