<strong>Introduction</strong><span><span><span style="font-family:;" "=""> <strong>:</strong></span></span></span><span><sp...<strong>Introduction</strong><span><span><span style="font-family:;" "=""> <strong>:</strong></span></span></span><span><span><span style="font-family:;" "="">Chronic liver disease (CLD) is a disease of public health importance. CLD is<b> </b>defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC).</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with<span> alpha-fetoprotein</span> (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des</span></span></span><span><span><span style="font-family:;" "="">-</span></span></span><span><span><span style="font-family:;" "="">gamma</span></span></span><span><span><span style="font-family:;" "="">-</span></span></span><span><span><span style="font-family:;" "="">carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><b><span style="font-family:;" "="">Materials and Methods</span></b></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">This study was a cross-sectional study and ethical clearance was obtained from the<b> </b>ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value < 0.05. AFP Quantitative test kit (alfabeto-RiakiDainabot Radioisotope laboratory, Japan) and DCP Qualitative test kit (<span>EiTest</span> MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><b><span style="font-family:;" "="">Results</span></b></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">Using a cut-off of 400</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. <b>Conclusion</b></span></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.</span></span></span>展开更多
AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical e...AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.展开更多
INTRODUCTION Hepatocellular carcinoma(HCC)is closely relatedwith hepatitis and cirrhosis.In order to investigatethe pathogenesis and early pathologic diagnosis ofHCC,HCC and related lesions were analyzedqualitively an...INTRODUCTION Hepatocellular carcinoma(HCC)is closely relatedwith hepatitis and cirrhosis.In order to investigatethe pathogenesis and early pathologic diagnosis ofHCC,HCC and related lesions were analyzedqualitively and quantitively by automatic imageanalysor and immunohistochemical assay.展开更多
Design: Retrospective analysis. Setting: East London Hospital. Subjects: 724 women who had maternal serum alphafetoprotein levels measured between 15 to 19 weeks gestation. Main outcome measure: The main outcome measu...Design: Retrospective analysis. Setting: East London Hospital. Subjects: 724 women who had maternal serum alphafetoprotein levels measured between 15 to 19 weeks gestation. Main outcome measure: The main outcome measures were defined as any case of preeclampsia, small-for-gestational age (SGA) birth- weight th centile, placental abruption, stillbirth or early neonatal death. Methods: Women with MSAFP > 2.0 Multiples of Median (MoM) were classified as screen positive. Results: 41 (5.7%) women developed preeclampsia. Women with MSAFP > 2.0 Multiples of the Median (MoM) were significantly more likely to develop preeclampsia (p th centile展开更多
Subjective: The purpose of investigating thecarcinohistogenesis of hepatocarcinoina and alphafetoprotein AFP expression in oncogenesis was to lay amorphological foundation for diagnosing and curinghepatocarcinoma. Met...Subjective: The purpose of investigating thecarcinohistogenesis of hepatocarcinoina and alphafetoprotein AFP expression in oncogenesis was to lay amorphological foundation for diagnosing and curinghepatocarcinoma. Methods: Experimental hepatocarcinoma of Wistar rats induced by 0.04% 3’-Me-DABand killed according to different dates. All the animalswere killed during a period of 36 weeks. Themorphologic changes of dynamics and expression of(AFP) with immunohistochemical method were observed.ReSults: Hyperplasia of oval cells was multipotentodifferential stem cell. It was further differentiated intotransitional cell and embryoid small liver cell, and thelatter can form pattern of atypical hyperplasia, whichscattered or crowded. The AFP in these cells showed wasa strong positive expression. The feature was differentbetween crowded small hepatocytes of atypicalhyperplasia and proliferative nodules of hepatocytes.The former was similar to morphologic character ofliver cell carcinoma. The oval cells were toward binaryduct differentiation to form fibroadenomatoid structure,and atypical hyperplasia was also seen in their epithelialcells. Of all the 58 experimental animals there were 26with hepatocarcinoma, among which 18 cases ofhepatocytic carcinoma and & mixed carcinoma werefollnd. The hepatocellular carcinoma showed AFPstrong .positive expression in the host hestocytes aroundcancer and hepatocytes of noll-neoplastic animals of alater experimental period also expressed various degreesof AFP positive. Conclusion: Atypical hyperplasia ofsmall hcpatocytes and epithelial cells of bile canaliculiwere the precancerous lesions of hepatocellularcarcinoma and bile duct carcinoma.展开更多
AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured h...AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.展开更多
BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-...BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.展开更多
Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC...Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.展开更多
AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early...AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.展开更多
BACKGROUND: The various combination of multiphase enhancement multislice spiral CT(MSCT) makes the diagnosis of a small hepatocellular carcinoma(s HCC) on the background of liver cirrhosis possible. This study was to ...BACKGROUND: The various combination of multiphase enhancement multislice spiral CT(MSCT) makes the diagnosis of a small hepatocellular carcinoma(s HCC) on the background of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein(AFP) level could increase the diagnostic efficiency for s HCC.METHODS: This study included 35 s HCC patients and 52 cirrhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists employing a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the diagnostic value of the three MSCT combination modes(arterial phase+portal-venous phase, arterial phase+delayed phase,arterial phase+portal-venous phase+delayed phase) and AFP levels for s HCC on the background of liver cirrhosis. RESULTS: The area under ROC curve(AUC), sensitivity,and specificity of the combination of arterial phase+portalvenous phase+delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase+portalvenous phase+delayed phase combination was significantly greater than that of the arterial phase+portal-venous phase(AUC=0.84, P=0.01) and arterial phase+delayed phase(AUC=0.85, P=0.03). Arterial phase+portal-venous phase had a smaller AUC(0.84) than arterial phase+delayed phase(0.85), but the difference was insignificant(P=0.15). After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for s HCC.CONCLUSIONS: The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for s HCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.展开更多
BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma...BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.展开更多
AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein(AFP) levels is a predictive factor for hepatocellular carcinoma(HCC) outcomes.METHODS We retrospectively analyzed 334 HCC patients w...AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein(AFP) levels is a predictive factor for hepatocellular carcinoma(HCC) outcomes.METHODS We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels:(1) the normal group, pre-AFP ≤ 20 ng/m L and post-AFP ≤ 20 ng/m L;(2) the response group, pre-AFP > 20 ng/m L and post-AFP decrease of ≥ 50% of pre-AFP; and(3) the non-response group, pre-AFP level > 20 ng/m L and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/m L but post-AFP >20 ng/m L RESULTS Univariate and multivariate analyses revealed thatmultiple tumors [hazard ratio(HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion(m VI)(HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the nonresponse group(HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrencefree survival. Similarly, multiple tumors(HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), m VI(HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group(HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The nonresponse group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group(P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes.CONCLUSION Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.展开更多
AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 &...AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.展开更多
AIM: To investigate the interaction between heat shock protein 70 (HSP70) and α-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL7402.METHODS: The expression and localization of HSP70 and AFP in...AIM: To investigate the interaction between heat shock protein 70 (HSP70) and α-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL7402.METHODS: The expression and localization of HSP70 and AFP in human HCC cell line BEL-7402 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. The interaction between HSP70 and AFP in HCC cells was analyzed by immunoprecipitation and Western blot.RESULTS: Immunocytochemical staining detection showed that HCC cell BEL-7402 expressed a high level of HSP70 and AFP synchronously. Both were stained in cell plasma.AFP existed in the immunoprecipitate of anti-HSP70 mAb,while there was HSP70 in the immunoprecipitate of antiAFP mAb.CONCLUSION: HSP70 chaperones AFP in human HCCcell BEL-7402. The interaction between HSP70 and AFP in human HCC cell can be a new route to study the pathogenesis and immunotherapy of HCC.展开更多
AIM: The goal of this study was to characterize the AlPreceptor, its possible signal transduction pathway and itsproliferative functions in human hepatoma cell line Bel 7402.METHODS: Cell proliferation enhanced by AFl...AIM: The goal of this study was to characterize the AlPreceptor, its possible signal transduction pathway and itsproliferative functions in human hepatoma cell line Bel 7402.METHODS: Cell proliferation enhanced by AFlP was detectedby MTT assay, 3H-thymidine incorporation and S-stsgepercentage of cell cycle analysis. With radioactive labeled 125 I-AFP for receptor binding assay; cAMP acctmuation, ProteinKinase A activity were detected by radioactive immunosorbentassay and the change of intracellular free calcium ([Ca2+ ], )was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncxgenes N- ras,p53, and p21ras in the cultured cells in vitro were detected byNorthem blotting and Western blotting respectively.RESULTS: It was demonstrated that AFP enhanced theproliferation of human hepatoma Bel 7402 cell in a dosedependlent fashion asshown in MTT assay, 3H-thymidineincorporation and S-phase percentage up to 2-fold. Twosubtypes of AFP receptors were identified in the cells withKds of 1.3 x 10-9 mol. L-1 and 9.9 x 10-8 mol. L-1 respectively.Pretreatnent of cells with AFP resulted-in a significantincrease (625 %) in cAMP accumulation. The activity ofprotein kinase A activity were increased up to 37.5, 122.6,73.7 and 61.2 % at treatment time point 2, 6, 12 and 24hours. The level of intracellular calcium were elevated afterthe treatment of alpha-fetoprotsin and achieved to 204 % at 4min. The results also showed that AFP (20 mg. L-1 ) couldupregulate the expression of N-ras oncogenes and p53 andp21ras in Bel 7402 cells. In the later case, the alteration ware 81.1%(12 h) and 97.3 %(12 h) respectively compared with control.CONCLUSION: These results demonstrate that AFP is apotential growth factor to promote the proliferation of humanhepatoma Bel 7402 cells. Its growth-regulatory effects aremediated by its specific plasma membrane receptorscoupled with its transmembrane signaling transductionthrough the pathway of cAMP-PKA and intracellular calciumto regulate the expression of oncogenes.展开更多
The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little inf ormation on a comparable CD8 and CD4 T cell response to a...The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little inf ormation on a comparable CD8 and CD4 T cell response to a tumor antigen in liver cancer patients. Here, we re-examine the kinetic and the pattern of T helper 1 and cytotoxic T lymphocyte responses to alpha-fetoprotein (AFP),a tumor rejection antigen in hepatocellular carcinoma (HCC). Then, we discuss the possibility of using AFP-based immunotherapy in combination with necrotizing treatments in HCC patients.展开更多
AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples.METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the fol...AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples.METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens: AFP, β-catenin, p53, CD44, MSH-2,MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups.RESULTS: Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nuclear p53 staining were AFP positive, while seven tumors with nuclear β-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and dinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples.CONCLUSION: AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear β-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data onin vivo human tumors.展开更多
Hepatocellular carcinoma(HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic...Hepatocellular carcinoma(HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumorspecific reporter gene expression driven by an alphafetoprotein(AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.展开更多
AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patie...AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival.METHODS Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/m L, high AFP level was defined as AFP value ≥ 10 to < 400 ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05.RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceaseddonor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/m L(n = 83); Group B, AFP ≥ 10 to < 400 ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger(A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria(P = 0.010). Poor differentiation and vascular permeation were also more common in this group(P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival(A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/m L for AFP(C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/m L was shown to affect the overall survival of the patients.CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/m L was associated with disease recurrence, and AFP level of 105 ng/m L was found to be the cut-off value for overall survival difference.展开更多
AIM The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS The effect of AFP on the p...AIM The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722×10-9M (Bmax=12810 sites per cell) and 8.931× 10-SM (Bmax=l19700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.展开更多
文摘<strong>Introduction</strong><span><span><span style="font-family:;" "=""> <strong>:</strong></span></span></span><span><span><span style="font-family:;" "="">Chronic liver disease (CLD) is a disease of public health importance. CLD is<b> </b>defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC).</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with<span> alpha-fetoprotein</span> (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des</span></span></span><span><span><span style="font-family:;" "="">-</span></span></span><span><span><span style="font-family:;" "="">gamma</span></span></span><span><span><span style="font-family:;" "="">-</span></span></span><span><span><span style="font-family:;" "="">carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><b><span style="font-family:;" "="">Materials and Methods</span></b></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">This study was a cross-sectional study and ethical clearance was obtained from the<b> </b>ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value < 0.05. AFP Quantitative test kit (alfabeto-RiakiDainabot Radioisotope laboratory, Japan) and DCP Qualitative test kit (<span>EiTest</span> MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><b><span style="font-family:;" "="">Results</span></b></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">Using a cut-off of 400</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "="">The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. <b>Conclusion</b></span></span></span><span><span><b><span style="font-family:;" "="">: </span></b></span></span><span><span><span style="font-family:;" "="">Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.</span></span></span>
基金Supported by The National Natural Science Foundation of China,No.30671856,30772536 and 81072710Beijing Natural Science Foundation,No.7101006+2 种基金the state key project for infectious diseases,2008ZX10002-015,2008ZX10002-005-3Beijing Science and Technology Commission,Z111107058811067High-Level Talent Academic Leader Training Program,(2011-2-09)
文摘AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.
基金the Applied and Basic Scientific Research Fund of Yunnan Province,No.94C027Q.
文摘INTRODUCTION Hepatocellular carcinoma(HCC)is closely relatedwith hepatitis and cirrhosis.In order to investigatethe pathogenesis and early pathologic diagnosis ofHCC,HCC and related lesions were analyzedqualitively and quantitively by automatic imageanalysor and immunohistochemical assay.
文摘Design: Retrospective analysis. Setting: East London Hospital. Subjects: 724 women who had maternal serum alphafetoprotein levels measured between 15 to 19 weeks gestation. Main outcome measure: The main outcome measures were defined as any case of preeclampsia, small-for-gestational age (SGA) birth- weight th centile, placental abruption, stillbirth or early neonatal death. Methods: Women with MSAFP > 2.0 Multiples of Median (MoM) were classified as screen positive. Results: 41 (5.7%) women developed preeclampsia. Women with MSAFP > 2.0 Multiples of the Median (MoM) were significantly more likely to develop preeclampsia (p th centile
文摘Subjective: The purpose of investigating thecarcinohistogenesis of hepatocarcinoina and alphafetoprotein AFP expression in oncogenesis was to lay amorphological foundation for diagnosing and curinghepatocarcinoma. Methods: Experimental hepatocarcinoma of Wistar rats induced by 0.04% 3’-Me-DABand killed according to different dates. All the animalswere killed during a period of 36 weeks. Themorphologic changes of dynamics and expression of(AFP) with immunohistochemical method were observed.ReSults: Hyperplasia of oval cells was multipotentodifferential stem cell. It was further differentiated intotransitional cell and embryoid small liver cell, and thelatter can form pattern of atypical hyperplasia, whichscattered or crowded. The AFP in these cells showed wasa strong positive expression. The feature was differentbetween crowded small hepatocytes of atypicalhyperplasia and proliferative nodules of hepatocytes.The former was similar to morphologic character ofliver cell carcinoma. The oval cells were toward binaryduct differentiation to form fibroadenomatoid structure,and atypical hyperplasia was also seen in their epithelialcells. Of all the 58 experimental animals there were 26with hepatocarcinoma, among which 18 cases ofhepatocytic carcinoma and & mixed carcinoma werefollnd. The hepatocellular carcinoma showed AFPstrong .positive expression in the host hestocytes aroundcancer and hepatocytes of noll-neoplastic animals of alater experimental period also expressed various degreesof AFP positive. Conclusion: Atypical hyperplasia ofsmall hcpatocytes and epithelial cells of bile canaliculiwere the precancerous lesions of hepatocellularcarcinoma and bile duct carcinoma.
基金Supported by the National Natural Science Foundation of China,No. 30260117 and 30271174 the Natural Science Foundation of Hainan Province, No. 30315 the Educational Key Foundation of Hainan Province, No. 200322 the Nursery Foundation of Hainan Medical College, No. 200202
文摘AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.
基金supported by grants from the National High Technology Research and Development Program of China(2007AA02Z461)the China National Key Projects for Infectious Disease (2008ZX10002-021)
文摘BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.
基金supported in part by the National Natural Sci-ence Foundation of China(81472284 and 81672699)Shanghai Pujiang Program(16PJD004)
文摘Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
文摘AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.
基金supported by grants from the National Natural Science Foundation of China(81301275,81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Heilongjiang Province Foundation for Returness(LC2013C38)
文摘BACKGROUND: The various combination of multiphase enhancement multislice spiral CT(MSCT) makes the diagnosis of a small hepatocellular carcinoma(s HCC) on the background of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein(AFP) level could increase the diagnostic efficiency for s HCC.METHODS: This study included 35 s HCC patients and 52 cirrhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists employing a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the diagnostic value of the three MSCT combination modes(arterial phase+portal-venous phase, arterial phase+delayed phase,arterial phase+portal-venous phase+delayed phase) and AFP levels for s HCC on the background of liver cirrhosis. RESULTS: The area under ROC curve(AUC), sensitivity,and specificity of the combination of arterial phase+portalvenous phase+delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase+portalvenous phase+delayed phase combination was significantly greater than that of the arterial phase+portal-venous phase(AUC=0.84, P=0.01) and arterial phase+delayed phase(AUC=0.85, P=0.03). Arterial phase+portal-venous phase had a smaller AUC(0.84) than arterial phase+delayed phase(0.85), but the difference was insignificant(P=0.15). After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for s HCC.CONCLUSIONS: The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for s HCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.
文摘BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.
文摘AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein(AFP) levels is a predictive factor for hepatocellular carcinoma(HCC) outcomes.METHODS We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels:(1) the normal group, pre-AFP ≤ 20 ng/m L and post-AFP ≤ 20 ng/m L;(2) the response group, pre-AFP > 20 ng/m L and post-AFP decrease of ≥ 50% of pre-AFP; and(3) the non-response group, pre-AFP level > 20 ng/m L and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/m L but post-AFP >20 ng/m L RESULTS Univariate and multivariate analyses revealed thatmultiple tumors [hazard ratio(HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion(m VI)(HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the nonresponse group(HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrencefree survival. Similarly, multiple tumors(HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), m VI(HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group(HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The nonresponse group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group(P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes.CONCLUSION Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.
文摘AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.
基金Supported by the Research Fund for Young Scholars of Beijing, No. 02120031 and Research Program of Beijing Education Committee, No. 0410025002
文摘AIM: To investigate the interaction between heat shock protein 70 (HSP70) and α-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL7402.METHODS: The expression and localization of HSP70 and AFP in human HCC cell line BEL-7402 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. The interaction between HSP70 and AFP in HCC cells was analyzed by immunoprecipitation and Western blot.RESULTS: Immunocytochemical staining detection showed that HCC cell BEL-7402 expressed a high level of HSP70 and AFP synchronously. Both were stained in cell plasma.AFP existed in the immunoprecipitate of anti-HSP70 mAb,while there was HSP70 in the immunoprecipitate of antiAFP mAb.CONCLUSION: HSP70 chaperones AFP in human HCCcell BEL-7402. The interaction between HSP70 and AFP in human HCC cell can be a new route to study the pathogenesis and immunotherapy of HCC.
基金National Natural Science Foundation of China,No.39760077
文摘AIM: The goal of this study was to characterize the AlPreceptor, its possible signal transduction pathway and itsproliferative functions in human hepatoma cell line Bel 7402.METHODS: Cell proliferation enhanced by AFlP was detectedby MTT assay, 3H-thymidine incorporation and S-stsgepercentage of cell cycle analysis. With radioactive labeled 125 I-AFP for receptor binding assay; cAMP acctmuation, ProteinKinase A activity were detected by radioactive immunosorbentassay and the change of intracellular free calcium ([Ca2+ ], )was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncxgenes N- ras,p53, and p21ras in the cultured cells in vitro were detected byNorthem blotting and Western blotting respectively.RESULTS: It was demonstrated that AFP enhanced theproliferation of human hepatoma Bel 7402 cell in a dosedependlent fashion asshown in MTT assay, 3H-thymidineincorporation and S-phase percentage up to 2-fold. Twosubtypes of AFP receptors were identified in the cells withKds of 1.3 x 10-9 mol. L-1 and 9.9 x 10-8 mol. L-1 respectively.Pretreatnent of cells with AFP resulted-in a significantincrease (625 %) in cAMP accumulation. The activity ofprotein kinase A activity were increased up to 37.5, 122.6,73.7 and 61.2 % at treatment time point 2, 6, 12 and 24hours. The level of intracellular calcium were elevated afterthe treatment of alpha-fetoprotsin and achieved to 204 % at 4min. The results also showed that AFP (20 mg. L-1 ) couldupregulate the expression of N-ras oncogenes and p53 andp21ras in Bel 7402 cells. In the later case, the alteration ware 81.1%(12 h) and 97.3 %(12 h) respectively compared with control.CONCLUSION: These results demonstrate that AFP is apotential growth factor to promote the proliferation of humanhepatoma Bel 7402 cells. Its growth-regulatory effects aremediated by its specific plasma membrane receptorscoupled with its transmembrane signaling transductionthrough the pathway of cAMP-PKA and intracellular calciumto regulate the expression of oncogenes.
基金Supported by a project grant from Association for International Cancer Research
文摘The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little inf ormation on a comparable CD8 and CD4 T cell response to a tumor antigen in liver cancer patients. Here, we re-examine the kinetic and the pattern of T helper 1 and cytotoxic T lymphocyte responses to alpha-fetoprotein (AFP),a tumor rejection antigen in hepatocellular carcinoma (HCC). Then, we discuss the possibility of using AFP-based immunotherapy in combination with necrotizing treatments in HCC patients.
基金Supported by the National Science Foundation of Hungary, No.OTKA 42674
文摘AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples.METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens: AFP, β-catenin, p53, CD44, MSH-2,MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups.RESULTS: Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nuclear p53 staining were AFP positive, while seven tumors with nuclear β-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and dinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples.CONCLUSION: AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear β-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data onin vivo human tumors.
基金Supported by Korea Science and Engineering Foundation,No.2012M2A2A7013480 and No.2013M2C2A1074238
文摘Hepatocellular carcinoma(HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumorspecific reporter gene expression driven by an alphafetoprotein(AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.
文摘AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival.METHODS Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/m L, high AFP level was defined as AFP value ≥ 10 to < 400 ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05.RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceaseddonor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/m L(n = 83); Group B, AFP ≥ 10 to < 400 ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger(A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria(P = 0.010). Poor differentiation and vascular permeation were also more common in this group(P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival(A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/m L for AFP(C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/m L was shown to affect the overall survival of the patients.CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/m L was associated with disease recurrence, and AFP level of 105 ng/m L was found to be the cut-off value for overall survival difference.
基金This work was supported by National NaturalScience Fundation of China(No.39760077).
文摘AIM The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722×10-9M (Bmax=12810 sites per cell) and 8.931× 10-SM (Bmax=l19700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.
