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1.
J Cancer ; 10(10): 2299-2311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258733

RESUMO

Background: Lymphocytes were reported to play a significant part in host anticancer immune responses and influence tumour prognosis. Few studies have focused on the prognostic values of aspartate aminotransferase (AST) to lymphocyte ratio (ALRI), aspartate aminotransferase to platelet count ratio index (APRI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) treated with palliative treatments. Methods: Five hundred and ninety-eight HCC patients treated with palliative therapies were retrospectively analysed. We randomly assigned patients into the training cohort (429 patients) and the validation cohort I (169 patients). Receiver operating characteristic (ROC) curves were used to identify the best cut-off values for the ALRI, APRI and SII in the training cohort and the values were further validated in the validation cohort I. Correlations between ALRI and other clinicopathological factors were also analysed. A prognostic nomogram including ALRI was established. We validated the prognostic value of the ALRI, SII and APRI with two independent cohorts, the validation cohort II of 82 HCC patients treated with TACE and the validation cohort III of 150 HCC patients treated with curative resection. In the training cohort and all the validation cohorts, univariate analyses by the method of Kaplan-Meier and multivariate analysis by Cox proportional hazards regression model were carried out to identify the independent prognostic factors. Results: The threshold values of ALRI, APRI and SII were 86.3, 1.37 and 376.4 respectively identified by ROC curve analysis in the training cohort. Correlation analysis showed that ALRI>86.3 was greatly associated with higher rates of Child-Pugh B&C, portal vein tumor thrombosis (PVTT) and ascites (P < 0.05). Correspondingly, ALRI level of HCC patients with Child-Pugh B&C, PVTT and ascites was evidently higher than that of HCC patients with Child-Pugh A, without PVTT and without ascites (P < 0.001). In the training cohort and the validation cohort I, II, III, the OS of patients with ALRI >86.3 was obviously shorter than patients with ALRI ≤86.3 (P <0.001). We identified ALRI as an independent prognostic factor by univariate and multivariate analyses both in training Cohort (HR=1.481, P=0.004), validation cohort I (HR=1.511, P=0.032), validation cohort II (HR=3.166, P=0.005) and validation cohort III (HR=3.921, P=0.010). The SII was identified as an independent prognostic factor in training cohort (HR=1.356, P=0.020) and the validation cohort II (HR=2.678, P=0.002). The prognostic nomogram including ALRI was the best in predicting 3-month, 6-month, 1-year, 2-year survival And OS among TNM, ALRI, ALRI-TNM and nomogram. Conclusions: The ALRI was a novel independent prognostic index for the HCC patients treated with palliative treatments.

2.
Am J Cancer Res ; 9(6): 1254-1265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285957

RESUMO

In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment.

3.
J Exp Clin Cancer Res ; 38(1): 196, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088567

RESUMO

BACKGROUND: Deregulation of protein translation control is a hallmark of cancers. Eukaryotic initiation factor 4A2 (EIF4A2) is required for mRNA binding to ribosome and plays an important role in translation initiation. However, little is known about its functions in colorectal cancer (CRC). METHODS: Analysis of CRC transcriptome data from TCGA identified that EIF4A2 was associated with poor prognosis. Immunohistochemistry study of EIF4A2 was carried out in 297 paired colorectal tumor and adjacent normal tissue samples. In vitro and in vivo cell-biological assays were performed to study the biological functions of EIF4A2 on experimental metastasis and sensitivity to oxaliplatin treatment. Bioinformatic prediction, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were carried out to unveil the transcription factor of EIF4A2 regulation. RESULTS: EIF4A2 Expression is significantly higher in colorectal tumors. Multivariate analysis suggests EIF4A2 as an independent predictor of overall, disease-free and progression-free survival. Dysfunction of EIF4A2 by genetic knock-down or small-molecule inhibitor silvestrol dramatically inhibited CRC invasion and migration, sphere formation and enhanced sensitivity to oxaliplatin treatment in vitro and in vivo. Notably, EIF4A2 knock-down also suppressed lung metastasis in vivo. qRT-PCR and immunoblotting analyses identified c-Myc as a downstream target and effector of EIF4A2. ChIP and dual-luciferase reporter assays validated the bioinformatical prediction of ZNF143 as a specific transcription factor of EIF4A2. CONCLUSIONS: EIF4A2 promotes experimental metastasis and oxaliplatin resistance in CRC. Silvestrol inhibits tumor growth and has synergistic effects with oxaliplatin to induce apoptosis in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fator de Iniciação 4A em Eucariotos/metabolismo , Oxaliplatina/farmacologia , Adulto , Idoso , Animais , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Cancer ; 9(19): 3467-3478, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310503

RESUMO

Background: We have previously reported the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) for advanced hepatocellular carcinoma (HCC) patients who are not receiving any standard anticancer therapy. However, the prognostic value of the AAPR for HCC patients treated with trans-catheter arterial chemoembolization therapy (TACE) was not investigated. Methods: We retrospectively analysed 372 HCC patients treated with TACE (the training cohort) and applied receiver operating characteristic curves (ROC curves) to identify the best cut-off value for the AAPR in this cohort. Then, univariate analyses by the Kaplan-Meier method and multivariate analysis by a Cox proportional hazards regression model were conducted. Both comparisons of the ROC curves and the likelihood ratio test (LRT) were employed to evaluate the abilities of different factors in predicting the survival of patients in this cohort. Finally, the prognostic value of the AAPR was validated in two cohorts: one included 202 HCC patients treated with supportive care (validation cohort I), and the other included 82 HCC patients treated with TACE (validation cohort II). Results: We identified 0.439 as the best cut-off value of the AAPR by ROC curve analysis. An AAPR > 0.439 was significantly correlated with a lower frequency of Child-Pugh grade B, portal vein tumour thrombus (PVTT), T3-4 and lymph node metastasis (P < 0.05). The median overall survival (OS) of the patients with an AAPR > 0.439 was significantly longer than that of those with an AAPR ≤ 0.439 (58.4 m vs 17.8 m, respectively, P < 0.001). The AAPR was identified as an independent prognostic factor after univariate and multivariate analyses (HR = 0.636, P = 0.003). The independent prognostic value of the AAPR was also confirmed in validation cohorts I and II. Additionally, we substituted the AAPR for the Child-Pugh grade in the CLIP system and integrated the AAPR into the TNM system. We found that the area under the curve (AUC) of the AAPR-CLIP system was significantly larger than that of the CLIP and the TNM when predicting 3-month, 6-month, 1-year and 2-year survival (P < 0.05). There was no significant difference between the AUCs for the AAPR-CLIP and the AAPR-TNM. The LRT suggested that both AAPR-CLIP and AAPR-TNM had significantly larger χ2 values and smaller AIC values than that of their corresponding primary system (P < 0.05). Conclusions: The AAPR was an independent prognostic index for the HCC patients treated with TACE. Both AAPR-CLIP and AAPR-TNM outperformed their corresponding primary system in predicting OS in the current study.

5.
J Cancer ; 9(13): 2380-2388, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30026834

RESUMO

Background: The Cancer of the Liver Italian Program (CLIP) score is commonly used for prognosis prediction of hepatocellular carcinoma (HCC). The CLIP includes the Child-Pugh grade, which is relatively subjective, for hepatic encephalopathy assessment. A newly developed scoring system called albumin-bilirubin grade (ALBI grade), consists of albumin and bilirubin to assess liver function reserve objectively. Here, we substituted the ALBI grade for the Child-Pugh grade to establish the ALBI-CLIP scoring system and validated its prognostic value in hepatitis B virus (HBV)-related HCC patients treated with trans-catheter arterial chemoembolization (TACE) therapy. Methods: We retrospectively analyzed HBV-related HCC patients who received TACE therapy. Baseline characteristics were collected and evaluated to classify patients according to ALBI-CLIP, CLIP and TNM systems. Univariate analyses using the Kaplan-Meier method and the log-rank test, as well as multivariate analysis using the Cox proportional hazards regression model, were conducted to detect independent prognostic factors for overall survival. Receiver operating characteristic (ROC) curves and a likelihood ratio test (LRT) were both utilized to compare the values of ALBI-CLIP, CLIP and TNM staging systems in predicting survival. Results: With a total of 389 patients included in the current study, 301 (77.4%) and 88 (22.6%) were classified as Child-Pugh grade A and B, respectively. However, 152 (39.1%), 227 (58.4%) and 10 (2.5%) patients were correspondingly classified into ALBI grade 1, 2 and 3. The areas under the curves of ALBI-CLIP, CLIP and TNM systems were 0.804, 0.778 and 0.734, respectively, for predicting 3-month survival; 0.796, 0.778 and 0.733, respectively, for 6-month survival; 0.697, 0.687 and 0.644, respectively, for 1-year survival; and 0.618, 0.612 and 0.569, respectively, for 2-year survival. The LRT indicated that the ALBI-CLIP and the CLIP had similar values of χ2 and Akaike information criterion (AIC) while the TNM system had the smallest χ2 value (χ2 = 12.1, 11.9, 10.5; AIC = 2620.2, 2620.5, 2621.1 for ALBI-CLIP, CLIP and TNM, respectively). Conclusions: In conclusion, our present study suggested that the ALBI-CLIP scoring system retained the prognostic value of the CLIP in HBV-related HCC treated with TACE therapy.

6.
Oncol Lett ; 15(1): 855-862, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29403561

RESUMO

The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment.

7.
J Cancer ; 9(3): 512-520, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29483956

RESUMO

Purpose: Tumour cells produce energy through glycolysis and lactate dehydrogenase (LDH) is a key part of glycolysis. Elevation of serum LDH may indicate poor prognosis in primary duodenum adenocarcinoma. We aim to explore the prognostic significance of LDH in this disease. Methods and materials: Two hundred forty-four patients diagnosed with primary duodenum adenocarcinoma who were treated at the Sun Yat-sen Cancer Center from February 1996 to January 2016 were retrospectively analysed. We collected routine clinical data, including baseline LDH. Patients were classified into a normal LDH group (≤ 245U/L) and higher LDH group (>245U/L). Correlations of the LDH level and other clinicopathological characteristics were explored using the Chi-square test. Prognostic factors for overall survival were identified using univariate and multivariate analyses. Results: Two hundred seven patients (84.9%) had normal LDH levels, while 37 patients (15.1%) had abnormally high LDH levels. Higher LDH levels were significantly associated with more distant metastasis, node metastasis, poor differentiation and TNM stage Ⅲ-Ⅳ (P<0.05). Consistently, patients with node metastasis, poor differentiation and TNM stageⅢ-Ⅳ had a significantly higher median LDH level (P<0.05). The median survival of patients in the higher LDH group was significantly shorter than that of the patients in the normal LDH group (16.3 m vs. 42.5 m, P=0.02). Using multivariate analysis, LDH, age and radical surgery were independent prognostic factors associated with overall survival(OS) (HR=1.571, P=0.036 for LDH; HR=1.514, P=0.013 for age; HR=0.248, P<0.0001 for radical surgery, respectively). Conclusions: For the first time, our research suggests that baseline serum LDH is an independent prognostic factor in primary duodenum adenocarcinoma patients and elevated baseline serum LDH indicates a poor prognosis.

8.
Biomed Pharmacother ; 97: 195-202, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29091866

RESUMO

BACKGROUND: Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1's capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. METHODS: The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. RESULTS: The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P=0.035), high levels of serum AFP (P=0.049), more frequency of node metastasis (P=0.015), later TNM stage (P=0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P=0.021), while LC3B were suggested to be negatively related with patients' PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P=0.002) and shorter 5-year progression free survival (PFS)(P=0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. CONCLUSION: ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/biossíntese , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Hepáticas/metabolismo , Proteínas Associadas aos Microtúbulos/biossíntese , Adulto , Carcinoma Hepatocelular/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida/tendências
9.
Immunology ; 154(1): 144-155, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29211299

RESUMO

A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1+  CD15+ PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1+  CD15+ PMN-MDSCs significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner with LOX-1-  CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1 + CD15+ PMN were higher in LOX-1+  CD15+ PMN-MDSCs than LOX-1-  CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX-1+  CD15+ PMN-MDSCs were positively related to overall survival. Above all, LOX-1+  CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Estresse do Retículo Endoplasmático , Fucosiltransferases/metabolismo , Antígenos CD15/metabolismo , Neoplasias Hepáticas/metabolismo , Células Supressoras Mieloides/metabolismo , Receptores Depuradores Classe E/metabolismo , Arginase/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Humanos , Interferons/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Ativação Linfocitária , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo
10.
Oncol Lett ; 14(5): 6277-6284, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29113278

RESUMO

Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

11.
Oncol Lett ; 14(2): 2089-2096, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789436

RESUMO

The inflammatory microenvironment serves an important function in the progression of hepatocellular carcinoma (HCC). Peripheral blood lymphocyte-to-monocyte ratio (LMR), as a novel inflammatory biomarker combining an estimate of host immune homeostasis with the tumor microenvironment, has been identified to be a predictor of clinical outcomes in a number of malignancies. The present study aimed at investigating the prognostic value of LMR in patients with hepatitis B virus (HBV)-associated advanced HCC. A total of 174 patients with HBV-associated advanced HCC, without fever or signs of infections, were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival time. Univariate and multivariate analysis was performed using Cox's proportional hazards model. A threshold value was determined using a time-dependent receiver operating characteristic curve. Univariate and multivariate analysis identified LMR as an independent prognostic factor in overall survival (OS) time in patients with HBV-associated advanced HCC (P<0.05). The threshold value of LMR was 2.22. All patients were divided into either a low LMR group (≤2.22) or a high LMR group (>2.22). The OS time of the high LMR group was significantly longer compared with the low LMR group (P<0.001). Patients in the high LMR group exhibited a significantly increased 3-month and 6-month OS rate, compared with that of the patients within the low LMR group (P<0.001). An increased level of LMR was significantly associated with the presence of metastasis, ascites and increased tumor size (P<0.01). LMR is an independent prognostic factor of HBV-associated advanced HCC patients and an increased baseline LMR level indicates an improved prognosis.

12.
Oncol Lett ; 14(1): 705-714, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693224

RESUMO

The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P<0.05) for predicting 6-month mortality. The χ2 values from the LRTs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0, 46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1, respectively. CLIP exhibited the highest χ2 value and lowest AIC value, indicating that CLIP has the highest predictive value of cumulative survival rate. In the selected patients of the present study, CLIP was the staging system best able to predict 3- and 6-month and overall survival rates. CIS ranked second in predicting 3-month mortality.

13.
Medicine (Baltimore) ; 96(26): e7373, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28658162

RESUMO

BACKGROUND & AIMS: Nutritional interventions for malnutrition in cancer patients can be helpful. However, concise intervention recommendations remain controversial. Thus, the aim of this study was to report on a nutrition intervention conducted by a multidisciplinary team of specialist nurses and to explore the effect of nutritional intervention on cancer patients. METHODS: This prospective clinical trial study enrolled 110 colorectal cancer patients undergoing chemotherapy. The patients were evaluated upon admission using the 2002 Nutritional Risk Screening system (NRS-2002). The patients were randomly divided into intervention and control groups including 55 patients each. Patients in the control group were administered a normal diet, while those in the intervention group received individual recipes developed by a team of professional nurses, clinical doctors, dietitian, family caregivers, and the patients themselves. Patient weight and serum albumin and prealbumin levels were compared between the 2 groups at different time points. RESULTS: There was a significant difference in patient weight and serum albumin and prealbumin levels before and after nutrition intervention in the intervention group (P < .05). In the control group, weight did not change during ordinary diet guidance. Serum albumin level was slightly improved after 12 cycles of chemotherapy, similar to the prealbumin results. There were statistically significant differences in serum albumin and prealbumin levels between the intervention and control groups after nutrition intervention (P < .05). However, there was no statistically significant difference in weight between the groups after nutrition intervention (P > .05). CONCLUSION: A multidisciplinary team approach for nutrition intervention conducted by specialist nurses improved prealbumin levels in colorectal cancer patients undergoing chemotherapy, with no weight change.


Assuntos
Neoplasias Colorretais/dietoterapia , Neoplasias Colorretais/tratamento farmacológico , Enfermeiras Especialistas , Equipe de Assistência ao Paciente , Biomarcadores Tumorais/sangue , Peso Corporal , Cuidadores , Neoplasias Colorretais/sangue , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Nutricionistas , Educação de Pacientes como Assunto , Albumina Sérica/análise , Resultado do Tratamento
14.
Oncotarget ; 8(28): 45391-45398, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28512268

RESUMO

BACKGROUND: Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients' personal will. OBJECTIVES: This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. RESULTS: While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. MATERIALS AND METHODS: Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients' awareness of their disease, and participation in an advance directive. CONCLUSIONS: Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive.


Assuntos
Diretivas Antecipadas , Tomada de Decisões , Neoplasias/epidemiologia , Neoplasias/psicologia , Preferência do Paciente , Adulto , Idoso , Conscientização , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Participação do Paciente
15.
Oncotarget ; 8(19): 31318-31328, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28412743

RESUMO

BACKGROUND: High recurrence rate after curative treatment is the major problem for hepatocellular carcinoma (HCC). Cytokine-induced killer cells (CIKs) therapy was extensively studied among HCC patients. However, the value of CIKs therapy was controversial. A meta-analysis was performed to investigate the efficacy of adjuvant CIKs after invasive treatments among HCC patients. METHODS: We searched online for literatures studying sequential CIKs therapy for HCC patients. Recurrence-free survival (RFS), progress-free survival (PFS) and overall survival (OS) were set as the main endpoints. Both overall and subgroup analysis were accomplished. RESULTS: A total of 12 clinical trials with 1,387 patients were included. The pooled analysis showed a significant improvement of RFS, PFS and OS in CIK group (HR 0.56, 95% CI 0.47-0.67, p<0.00001 for RFS; HR 0.53, 95% CI 0.40-0.69, p<0.00001 for PFS; HR 0.59, 95% CI 0.46-0.77, p<0.0001 for OS). The proportion of CD4+ T cells increased significantly, while CD8+ T cells decreased significantly after CIKs therapy (WMD 4.07, 95% CI 2.58-5.56, p<0.00001; WMD -2.84, 95% CI -4.67 to -1.01, p=0.002, respectively). No significant differences of adverse events between CIK and non-CIK group existed. CONCLUSIONS: Conventionally invasive therapies combined with CIKs therapy could improve the prognosis of HCC patients, especially for RFS and PFS, with mild side effects. Optimizing patient selection shall be the direction in future studies.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Células Matadoras Induzidas por Citocinas/transplante , Imunoterapia Adotiva , Neoplasias Hepáticas/terapia , Ásia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ensaios Clínicos como Assunto , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Viés de Publicação , Gestão da Segurança , Transplante Autólogo , Resultado do Tratamento
16.
Oncotarget ; 8(15): 24380-24388, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28412745

RESUMO

Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028-1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.


Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Neutrófilos/patologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Oncotarget ; 7(38): 61378-61389, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27542216

RESUMO

BACKGROUND AND AIMS: This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. RESULTS: The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). METHODS: A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. CONCLUSIONS: This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients.


Assuntos
Carcinoma Hepatocelular/mortalidade , Hepatectomia , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Nomogramas , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida
19.
Hum Pathol ; 53: 25-34, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26980034

RESUMO

As a special subtype of gastric carcinoma, Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. The Cancer Genome Atlas Research Network revealed that EBVaGC also has distinct molecular features: PIK3CA mutations, DNA hypermethylation, and JAK2, PD-L1, and PD-L2 amplification. Here, we evaluated PIK3CA, JAK2, PD-L1, and PD-L2 expression in 59 EBVaGC and 796 EBV-negative gastric carcinoma (EBVnGC) cases using immunohistochemistry and found that PIK3CA, JAK2, PD-L1, and PD-L2 were highly expressed in 75.9% and 48.8% (P<.001), 81.8% and 71.1% (P=.091), 92.5% and 84.8% (P=.132), and 98.1% and 89.7% (P=.049) of the EBVaGC and EBVnGC cases, respectively. However, the expression of PIK3CA, JAK2, PD-L1, or PD-L2 was not significantly associated with clinicopathological features or patient outcomes in EBVaGC. In contrast, in EBVnGC, high PIK3CA expression was significantly associated with indolent clinicopathological features and independently predicted better 5-year overall survival (57.8% versus 33.4%, P<.001). Our study indicated that the protein expression of the 4 characteristic molecules of EBVaGC was basically consistent with their genetic alterations, making them potential characteristic protein biomarkers and therapeutic targets of EBVaGC. The favorable impact of PIK3CA overexpression on survival found in this study gives us new insight into the clinical significance of PIK3CA in EBVnGC.


Assuntos
Adenocarcinoma/enzimologia , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Infecções por Vírus Epstein-Barr/virologia , Janus Quinase 2/análise , Fosfatidilinositol 3-Quinases/análise , Proteína 2 Ligante de Morte Celular Programada 1/análise , Neoplasias Gástricas/enzimologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Distribuição de Qui-Quadrado , China , Classe I de Fosfatidilinositol 3-Quinases , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA Viral/genética , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia
20.
Tumour Biol ; 37(4): 5265-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26561464

RESUMO

Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Doença Hepática Terminal/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Doença Hepática Terminal/sangue , Doença Hepática Terminal/epidemiologia , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Índice de Gravidade de Doença , Sódio/sangue , Análise de Sobrevida
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