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1.
Cell Metab ; 29(4): 886-900.e5, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30661930

RESUMO

Metabolic reprogramming plays an important role in supporting tumor growth. However, little is known about the metabolic alterations that promote cancer metastasis. In this study, we identify acyl-CoA thioesterase 12 (ACOT12) as a key player in hepatocellular carcinoma (HCC) metastasis. The expression of ACOT12 is significantly down-regulated in HCC tissues and is closely associated with HCC metastasis and poor survival of HCC patients. Gain- and loss-of-function studies demonstrate that ACOT12 suppresses HCC metastasis both in vitro and in vivo. Further mechanistic studies reveal that ACOT12 regulates the cellular acetyl-CoA levels and histone acetylation in HCC cells and that down-regulation of ACOT12 promotes HCC metastasis by epigenetically inducing TWIST2 expression and the promotion of epithelial-mesenchymal transition. Taken together, our findings link the alteration of acetyl-CoA with HCC metastasis and imply that ACOT12 could be a prognostic marker and a potential therapeutic target for combating HCC metastasis.

2.
Int J Surg ; 57: 45-53, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30075291

RESUMO

BACKGROUND: Preoperative serum inflammatory markers have been correlated with survival outcomes after resection of hepatocellular carcinoma (HCC). Whether they can predict microvascular invasion (MVI) in HCC is still unknown. This study aimed to evaluate the association of inflammatory markers with MVI, and develop a simple and inexpensive preoperative prediction model for MVI. METHODS: We developed a novel index using routine laboratory tests to predict MVI. The index was developed based on a study on patients with HCC, and validated in an internal cohort and another external cohort. The infiltration of CD8+ T cells in tumors was measured using immunohistochemistry. The prediction accuracy was evaluated with the area under the receiver operating characteristic curve (AUC). RESULTS: There were 165 patients in the training cohort, 107 patients in the internal validation cohort and 80 patients in the external validation cohort. On multivariable analysis in the training cohort, alkaline phosphatase (ALP) and lymphocyte count were independent predictors of MVI. Thus, the ALP-to-lymphocyte ratio (ALR) was developed. The AUCs of the ALR for MVI were higher than the other conventional clinical indices. An optimal cutoff point for the ALR of 69.9 stratified HCC patients into the high (≥69.9) and low (<69.9) groups. An ALR ≥69.9 was significantly associated with worse overall and disease-free survival outcomes. The performance of ALR was validated in the internal and in external cohorts. The CD8+ T cell counts were significantly higher in HCC in the ALR<69.9 groups. CONCLUSION: ALR was a simple, accurate and inexpensive alternative to predict MVI and an independent risk factor of prognosis for HCC patients. The dismal survival outcomes in patients with high ALR scores were related to decreased infiltrations of CD8+ T cells in tumors.


Assuntos
Algoritmos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Microvasos/patologia , Adulto , Idoso , Fosfatase Alcalina/sangue , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Valores de Referência , Estudos Retrospectivos , Fatores de Risco
3.
Cell Physiol Biochem ; 47(3): 1152-1166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29913454

RESUMO

BACKGROUND/AIMS: Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. METHODS: The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays. The effects of RA190 on the proliferation and survival of both established ICC cell lines and primary ICC cells were examined in vitro. Annexin V/propidium iodide staining, western blotting and immunohistochemical staining were performed. The in vivo anti-tumor effect of RA190 on ICC was validated in subcutaneous xenograft and patient-derived xenograft (PDX) models. RESULTS: ADRM1 levels were significantly higher in ICC tissues than in normal bile duct tissues. ICC patients with high ADRM1 levels had worse overall survival (hazard ratio [HR] = 2.383, 95% confidence interval [CI] =1.357 to 4.188) and recurrence-free survival (HR = 1.710, 95% CI =1.045 to 2.796). ADRM1 knockdown significantly inhibited ICC growth in vitro and in vivo. The specific inhibitor RA190 targeting ADRM1 suppressed proliferation and reduced cell vitality of ICC cell lines and primary ICC cells significantly in vitro. Furthermore, RA190 significantly inhibited the proteasome by inactivating ADRM1, and the consequent accumulation of ADRM1 substrates decreased the activating levels of NF-κB to aggravate cell apoptosis. The therapeutic benefits of RA190 treatment were further demonstrated in both subcutaneous implantation and PDX models. CONCLUSIONS: Our findings indicate that up-regulated ADRM1 was involved in ICC progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzilideno/farmacologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas de Neoplasias , Idoso , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo
4.
Genet Test Mol Biomarkers ; 22(2): 115-126, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29266978

RESUMO

BACKGROUND AND AIMS: The prognostic value of BRCA1-associated protein 1 (BAP1) expression in different cancer types remains controversial. The aim of this study was to identify the prognostic and clinicopathological significance of BAP1 gene expression. MATERIALS AND METHODS: The PubMed, Web of Science, and Embase databases were searched comprehensively for relevant studies. The pooled effects were calculated to investigate the association of BAP1 expression with cancer prognosis and clinicopathological features. The χ2 and I2 tests were performed to evaluate heterogeneity among the enrolled articles. If the p > 0.05 and I2 < 50%, a fixed-effects model was applied; and if the p < 0.05 and I2 > 50%, we used a random-effects model. RESULTS: A total of 26 studies covering 8043 patients were included in the meta-analysis. The correlation between BAP1 expression and patient survival was evaluated for 10 different cancer types. The pooled hazard ratio (HR) of BAP1 expression and overall survival (OS) was 0.83 (95% confidence interval [CI]: 0.61-1.12) with heterogeneity (I2 = 85.8%, p < 0.001), which indicated that the expression of BAP1 had no obvious impact on patient survival in the all-cancer cohort. However, subgroup analyses indicated that cancer type, rather than other parameters (geographic region, detection method, sample size, or comparison method), lead to this heterogeneity. BAP1 expression was a favorable predicative factor for OS in clear cell renal cell carcinoma (HR = 0.57, 95% CI: 0.47-0.69), non-small cell lung cancer (HR = 0.55, 95% CI: 0.32-0.96), and uveal melanoma (HR = 0.41, 95% CI: 0.27-0.62), while high expression of BAP1 was associated with poorer outcome in malignant pleural mesothelioma (HR = 2.03, 95% CI: 1.67-2.47). CONCLUSION: Our study revealed that BAP1 expression tends to have different prognostic values in different cancer types. Clinically, BAP1 may serve as a promising marker for prognostic prediction for certain cancer types.


Assuntos
Neoplasias/mortalidade , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico
5.
Mol Med Rep ; 16(2): 1785-1792, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28627641

RESUMO

Homeostasis of cholesterol is regulated by absorption in the intestine and synthesis in the liver. The authors previously demonstrated that OPN (osteopontin) exhibits the ability to alter hepatic cholesterol metabolism, thus affecting cholesterol gallstone formation in mice. The present study investigated the role of OPN in cholesterol gallstone formation, focusing on its effect on intestinal absorption of cholesterol. OPN gene knockout (OPN­/­) mice and wild­type mice were respectively fed with a chow or lithogenic diet (LD) for 8 weeks. Following an 8­week LD period, the incidence of gallstone, bile composition, level of serum and fecal lipids and the expression of intestinal associated genes were analyzed. OPN­/­ mice were protected from gallstone formation induced by 8 weeks' LD­feeding. This protective effect from OPN deficiency was associated with alterations in bile composition, including a reduced concentration of biliary cholesterol. Additionally, plasma cholesterol level was decreased in LD­fed OPN­/­ mice. The alterations primarily resulted from the decreased expression of intestinal Niemann­Pick C1­like (NPC1 L) 1, which is important in the intestinal absorption of cholesterol. The present study demonstrated that OPN deficiency reduced intestinal absorption of cholesterol by suppressing the expression of NPC1L1, thus protecting mice from cholesterol gallstone formation.


Assuntos
Colesterol/metabolismo , Cálculos Biliares/genética , Cálculos Biliares/prevenção & controle , Mucosa Intestinal/metabolismo , Proteínas de Membrana Transportadoras/genética , Osteopontina/deficiência , Animais , Ácidos e Sais Biliares/metabolismo , Peso Corporal , Vesícula Biliar/patologia , Íleo/patologia , Fígado/metabolismo , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos Knockout , Tamanho do Órgão , Osteopontina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
Tumour Biol ; 39(6): 1010428317699111, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28618948

RESUMO

BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/genética , Melanoma/genética , Prognóstico , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Especificidade de Órgãos , Neoplasias Uveais/patologia
9.
Cancer Cell ; 30(3): 444-458, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27569582

RESUMO

The mechanism of cancer metastasis remains poorly understood. Using gene profiling of hepatocellular carcinoma (HCC) tissues, we have identified GOLM1 as a leading gene relating to HCC metastasis. GOLM1 expression is correlated with early recurrence, metastasis, and poor survival of HCC patients. Both gain- and loss-of-function studies determine that GOLM1 acts as a key oncogene by promoting HCC growth and metastasis. It selectively interacts with epidermal growth factor receptor (EGFR) and serves as a specific cargo adaptor to assist EGFR/RTK anchoring on the trans-Golgi network (TGN) and recycling back to the plasma membrane, leading to prolonged activation of the downstream kinases. These findings reveal the functional role of GOLM1, a Golgi-related protein, in EGFR/RTK recycling and metastatic progression of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Receptores ErbB/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Adolescente , Adulto , Idoso , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Transfecção , Regulação para Cima , Adulto Jovem
10.
Sci Rep ; 6: 30215, 2016 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-27484115

RESUMO

The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments.


Assuntos
Ductos Biliares/fisiologia , Bile/química , Vesícula Biliar/metabolismo , Cálculos Biliares/patologia , Fígado/metabolismo , Osteopontina/metabolismo , Adenosina Trifosfatases/biossíntese , Animais , Bile/metabolismo , Colesterol 7-alfa-Hidroxilase/biossíntese , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteopontina/deficiência , Osteopontina/genética , Receptores Citoplasmáticos e Nucleares/biossíntese , Receptores Depuradores Classe B/biossíntese , Proteína de Ligação a Elemento Regulador de Esterol 2/biossíntese
11.
J Cell Mol Med ; 20(5): 903-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26820236

RESUMO

UNLABELLED: Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3' terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital-based case-control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03-1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13-2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non-cardia stomach cancer. Further combined analysis indicated men, smokers, or non-drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.


Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Expressão Gênica , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/patologia
12.
Cancer Biol Med ; 13(4): 459-468, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28154777

RESUMO

OBJECTIVE: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males. METHODS: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients. RESULTS: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2 expression showed poorer predictive efficiency in the 45-49 and 55-60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival (P < 0.0001) and recurrence time (P = 0.0001) in male patients. After excluding male patients in the 45-60 age group, the predictive efficiency was enhanced (n = 147, OS, P = 0.0002, TTR, P < 0.0001). CONCLUSIONS: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically (andropause age).

13.
Int J Oncol ; 45(2): 629-40, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24859810

RESUMO

Mammalian sterile-20-like kinase 4 (MST4) has been implicated in cell proliferation and differentiation. In a previous study, we found MST4 to be an important candidate gene for metastatic hepatocellular carcinoma (HCC); however, the molecular mechanism of the promoting role of MST4 in HCC metastasis is poorly understood. In this study, we show that high expression of MST4 was detected in highly invasive HCC cells and in human HCC specimens with vascular invasion. A high level of MST4, associated with large tumor size, microvascular invasion, presence of intrahepatic metastasis, and advanced TNM classification of malignant tumors stage, was an independent prognostic factor for overall survival (P=0.004) and time to recurrence (P=0.001) after hepatectomy. Knockdown of MST4 expression in HCC cells inhibited cell proliferation, colony formation, and invasion, whereas upregulation of MST4 significantly promoted these processes by promoting epithelial-mesenchymal transition (EMT), dependent on the activation of extracellular signal-regulated protein kinase (ERK) signaling pathways. Furthermore, the combination of MST4 and phosphorylated ERK was proven to have more power to predict the outcomes of HCC patients. This study presents clinical evidence for predicting the value of MST4 in HCC overall survival and recurrence and describes the key role of MST4 in facilitating the EMT process via regulating the activation of ERK, indicating its potential role as a target for postoperative adjuvant therapy for HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica/genética , Proteínas Serina-Treonina Quinases/biossíntese , Adulto , Biomarcadores Tumorais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos
14.
Clin Cancer Res ; 19(14): 3944-54, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23719264

RESUMO

PURPOSE: To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage. EXPERIMENTAL DESIGN: MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed. RESULTS: MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred. CONCLUSIONS: Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Fatores de Crescimento Neural/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Estudos de Coortes , Detecção Precoce de Câncer , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Midkina , Curva ROC , Resultado do Tratamento , Regulação para Cima , alfa-Fetoproteínas/metabolismo
15.
Ann Surg Oncol ; 20(3): 929-37, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23203407

RESUMO

BACKGROUND: Presurgery serum osteopontin (OPN) level has been demonstrated to correlate to tumor recurrence and survival of hepatocellular carcinoma (HCC) patients. This study investigated the postoperative dynamic changes of serum OPN level and its clinical significance in HCC patients. METHODS: Presurgery serum OPN levels were measured by enzyme-linked immunosorbent assay in cohort A of 179 HCC patients and were compared with the multiple controls including different kinds of liver diseases and healthy individuals. In cohort B of 110 patients with resectable HCCs, besides preoperative assays, serum OPN was monitored at 1 week, 1, and ≥2 months after operation. RESULTS: The baseline presurgery serum OPN of HCC patients was significantly higher than that of the patients with the other kinds of liver diseases (p < 0.0001). The prognostic values of presurgery serum OPN level in HCC patients were further confirmed. The postsurgery OPN levels were significantly elevated within 1 week after HCC resection, then decreased at 1 month and reached the nadir later than 2 months after operations. It increased again at the time of tumor recurrence, then declined after the second removal of recurrent HCCs. Moreover, postoperative OPN in α-fetoprotein-negative and -positive HCC patients had the same changing pattern; it only correlated to liver function and C-reactive protein level. CONCLUSIONS: After a transient fluctuation, serum OPN levels significantly decrease after curative resection of HCCs. Postoperative serum OPN could serve as a surrogate serologic biomarker for monitoring treatment response and tumor recurrence after HCC resection, including α-fetoprotein-negative ones.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Hepatite B/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/diagnóstico , Osteopontina/sangue , Proteína C-Reativa/metabolismo , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Hepatectomia , Hepatite B/cirurgia , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , alfa-Fetoproteínas/metabolismo
16.
Zhong Xi Yi Jie He Xue Bao ; 5(5): 531-5, 2007 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17854554

RESUMO

OBJECTIVE: Adopting methods of cell culture to explore the effects and mechanisms of Jianpi Bushen Huoxue Prescription (JPBSHXP), a traditional Chinese compound herbal medicine for strengthening spleen, reinforcing kidney and activating blood circulation, in inhibiting hematopoietic cells apoptosis in a mouse model of aplastic anemia (AA). METHODS: Blood serum of AA mice was made from an AA mouse model. Blood serums containing different traditional Chinese compound herbal medicine were made from rats after intragastric administration of JPBSHXP and its related decoctions, respectively. Bone marrow cells of normal mice were incubated by these blood serums for 24 hours, respectively. The apoptosis of the bone marrow cells were assayed by flow cytometry and transmission electron microscopy (TEM). RESULTS: It was indicated that the bone marrow cells of normal mice incubated with blood serum of AA mice displayed typical apoptosis. The apoptosis rates of bone marrow cells of the AA mice incubated by blood serum containing different traditional Chinese herbal medicine were decreased. The effect of Bushen (reinforcing kidey) Recipe was better than Jianpi (strengthening spleen) Recipe and Huoxue (activating blood circulation) Recipe, while the effect of JPBSHXP was the best. TEM results showed that the effect of Bushen Recipe was better than that of the Jianpi Recipe and the Huoxue Recipe, while the effect of JPBSHXP was the best. CONCLUSION: JPBSHXP and its related decoctions can significantly decrease the apoptosis rate of bone marrow mononuclear cells of the AA mice. It is inferred that JPBSHXP can promote bone marrow hematogenesis.


Assuntos
Anemia Aplástica/tratamento farmacológico , Apoptose/efeitos dos fármacos , Células da Medula Óssea/patologia , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Hematopoéticas/patologia , Anemia Aplástica/imunologia , Anemia Aplástica/patologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Ratos , Ratos Sprague-Dawley
17.
Chin J Integr Med ; 11(1): 60-4, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15975312

RESUMO

OBJECTIVE: To observe the clinical effect of Shengxueling (SXL) on idiopathic thrombocytopenic purpura (ITP), and study the possible mechanism. METHODS: Eighty-six cases of ITP were randomly divided into two groups. The SXL group, 56 patients treated with SXL, a traditinal Chinese medicine and 30 patients administered with prednisone were taken as control. Each group took drugs for 3 months and was under follow-up observation. RESULTS: In the SXL group, the total effective rate was 85.71%, similar to prednisone 83.33% (P > 0.05) for 3 months, but the total effective rate of SXL (91.07%) were obviously better than that of the control group (53.33%) (P < 0.01) for 6 months and had no obvious adverse reaction. The patients bleeding was alleviated or stopped, the general condition was improved. At the same time, blood platelet count (PLT) was increased, platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killers cells activity (NKa) increased, the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to maturation on bone marrow smear after treatment. All differences above were statistically significant. CONCLUSION: SXL is an effective and safe medicine for ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce the destruction of platelet, increase the number of platelet, promote the division and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, prevent and cure hemorrhagic tendency.


Assuntos
Medicina Tradicional Chinesa , Fitoterapia , Preparações de Plantas/uso terapêutico , Púrpura Trombocitopênica Idiopática/terapia , Adolescente , Adulto , Plaquetas/metabolismo , Medula Óssea/patologia , Feminino , Glucocorticoides/uso terapêutico , Hemorragia/etiologia , Hemorragia/fisiopatologia , Humanos , Imunoglobulinas/sangue , Interleucina-4/sangue , Células Matadoras Naturais/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fitoterapia/efeitos adversos , Preparações de Plantas/efeitos adversos , Contagem de Plaquetas , Prednisona/uso terapêutico , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/patologia , Subpopulações de Linfócitos T/patologia , Resultado do Tratamento
18.
Zhong Xi Yi Jie He Xue Bao ; 2(6): 421-5, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15539017

RESUMO

OBJECTIVE: To observe the clinical effect of Shengxueling Granule (SXLG) in treating idiopathic thrombocytopenic purpura (ITP), and to study its possible mechanism. METHODS: Eighty-six cases of ITP were divided into two groups randomly. Fifty-six cases in the treatment group were treated with SXLG, a traditional Chinese medicine, and 30 cases administered with Western medicine (prednisone) were taken as control. Patients in each group took drugs for three months and were under follow-up observation. RESULTS: In SXLG-treated group, the total effective rate in 3 months was 85.71%, similar to 83.33% in prednisone-treated group (P>0.05), while the total effective rate in 6 months in the SXLG-treated group was 91.07%, higher than 53.33% of the prednisone-treated group (P<0.01), and no obvious side-effects were observed. The patients' bleeding was alleviated or stopped, and their general condition was improved. And the blood platelet count (BPC) was increased, the platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killer cells activity (NKCA) increased, and the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocytes tended toward maturation on bone marrow smear after SXLG treatment. All differences above were statistically significant. CONCLUSION: SXLG is an effective and safe medicine for ITP. It can regulate the cellular immunity, inhibit the platelet antibody to reduce the destruction of the platelet and to increase the number of platelet, promote the differentiation and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, and prevent the hemorrhagic tendency.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Adulto , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Criança , Feminino , Humanos , Imunoglobulinas/efeitos dos fármacos , Imunoglobulinas/metabolismo , Interleucina-4/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Fitoterapia , Preparações de Plantas/uso terapêutico , Prednisona/uso terapêutico , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Resultado do Tratamento
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