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Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma 被引量:23
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作者 Peng Li Shan-Shan Wang +4 位作者 Hui Liu Ning Li Michael A McNutt Gang Li Hui-Guo Ding 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第41期4563-4571,共9页
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
关键词 alpha fetoprotein Receptor Hepatocellularcarcinoma MORTALITY Survival
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The Combined Diagnostic Accuracy of Serum Alpha Fetoprotein and Des-Gamma Carboxyprothrombin in Hepatocellular Carcinoma among Chronic Liver Disease Patients in Ilorin
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作者 A. M. Aliyu A. B. Olokoba +1 位作者 M. O. Bojuwoye K. C. Okonkwo 《Open Journal of Gastroenterology》 2021年第12期255-274,共20页
<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
关键词 Necro-Inflammation Liver Cirrhosis Hepatocellular Carcinoma alpha fetoprotein Des-Gamma-Carboxyprothrombin Enzyme-Linked Immunoassay PERCUTANEOUS Tumor Markers
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Computed morphometric analysis and expression of alpha fetoprotein in hepatocellular carcinoma and its related lesion 被引量:11
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作者 Li Juan Shen Zong Ji Zhang +5 位作者 Yang Ming Ou Hua Xian Zhang Run Huang Yun He Min Jie Wang Guo Shu Xu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第3期415-416,共2页
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
关键词 liver NEOPLASMS CARCINOMA HEPATOCELLULAR alpha fetoprotein MORPHOMETRY
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The relationship between second trimester alpha fetoprotein levels and adverse pregnancy outcome 被引量:4
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作者 Rebecca Allen Shemoon Marleen +2 位作者 Luxmi Velauthar Kevin Harrington Joseph Aquilina 《Open Journal of Obstetrics and Gynecology》 2013年第2期262-266,共5页
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
关键词 AFP alpha fetoprotein PRE-ECLAMPSIA Small for GESTATIONAL Age STILL BIRTH PLACENTAL ABRUPTION
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CARCINOHISTOGENESIS AND EXPRESSION OF ALPHA FETOPROTEIN IN EXPERIMENTAL HEPATOCARCINOMA
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作者 张继增 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1999年第2期118-121,共4页
Subjective: The purpose of investigating the carcinohistogenesis of hepatocarcinoma and alpha-fetoprotein AFP expression in oncogenesis was to lay a morphological foundation for diagnosing and curing hepatocarcinoma. ... Subjective: The purpose of investigating the carcinohistogenesis of hepatocarcinoma and alpha-fetoprotein AFP expression in oncogenesis was to lay a morphological foundation for diagnosing and curing hepatocarcinoma. Methods: Experimental hepato carcinoma of Wistar rats induced by 0.04% 3′-Me-DAB and killed according to different dates. All the animals were killed during a period of 36 weeks. The morphologic changes of dynamics and expression of (AFP) with immunohistochemical method were observed. Results: Hyperplasia of oval cells was multipotento-differential stem cell. It was further differentiated into transitional cell and embryoid small liver cell, and the latter can form pattern of atypical hyperplasia, which scattered or crowded. The AFP in these cells showed was a strong positive expression. The feature was different between crowded small hepatocytes of atypical hyperplasia and proliferative nodules of hepatocytes. The former was similar to morphologic character of liver cell carcinoma. The oval cells were toward biliary duct differentiation to form fibroadenomatoid structure, and atypical hyperplasia was also seen in their epithelial cells. Of all the 58 experimental animals there were 26 with hepatocarcinoma, among which 18 cases of hepatocytic carcinoma and 8 mixed carcinoma were found. The hepatocellular carcinoma showed AFP strong positive expression In the host hestocytes around cancer and hepatocytes of non-neoplastic animals of a later experimental period also expressed various degrees of AFP positive. Conclusion: Atypical hyperplasia of small hepatocytes and epithelial cells of bile canaliculi were the precancerous lesions of hepatocellular carcinoma and bile duct carcinoma. 展开更多
关键词 HEPATOCARCINOMA HYPERPLASIA alpha-fetoprotein Precancerous lesion
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CHANGES OF SERUM ALPHA FETOPROTEIN BEFORE AND AFTER RADIOIMMUNOTHERAPY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA
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作者 曾昭冲 汤钊猷 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1994年第2期83-90,共8页
Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of ̄(131)I anti HCC monoclonal ant... Thirtytwo patients with surgically verified unresectable table hepatocellular carcinoma (HCC) have been treated by radioimmunotherapy (RIT) using intrahepatic arterial administration of ̄(131)I anti HCC monoclonal antibody (Hepama1) combined with hepetic artery ligation. Twenty of them had abnormal serum alpha fetoprotein (AFP,>20 ng/ml). Single photon emission computed tomography (SPECT) scan and quantitative assay of AFP were performed after RIT. The results revealed that when the tumor to liver ratio (T/L) was higher than 3.5 (Group A , n =3) , the serum AFP level declined markedly and then kept in stable for a tongtime; when the T/L ratio was less than 1.2 (Group C ,n=5), the serum AFP level did not change evidently within 2 months postinfusion; while the T/L ratio was between 1. 2 3. 5 (Group B, n= 12) , the serum AFP level increased transiently and then decreased within 2 4 weeks postinfusion. Sequentiat resection was achieved in all of the 3 patients of Group A, in 6 patients (50%) of Group B, and none in Group C. The correlation of serum AFP and effective treatment demonstrates the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for HCC and T/L ratio might be a good indicator to predict tumor response to RIT in patients with 展开更多
关键词 RADIOIMMUNOTHERAPY alpha fetoprotein Hepatoma Monoclonal antibody Proliferation.
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The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells 被引量:27
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作者 MENG SEN LI, PING FENG LI, FBI YI YANG, SHI PENG HE, Guo GUANG DU, GANG LI1 Department of Biochemistry and Molecular Biology, 2 Department of Biophysics, Health Science Center, Peking University, Beijing 100083, China 《Cell Research》 SCIE CAS CSCD 2002年第2期151-156,共6页
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... 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 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 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
关键词 3T3 Cells Animals Cell Division Cyclic AMP Cyclic AMP-Dependent Protein Kinases Dose-Response Relationship Drug Humans Mice Receptors Peptide Research Support Non-U.S. Gov't Signal Transduction Time Factors alpha-fetoproteinS
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Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance 被引量:19
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作者 Xiao-Feng Zhang, Zheng-Feng Yin, Kui Wang, Zong-Qin Zhang, Hai-Hua Qian,Le-Hua ShiAuthor Affiliations: The 4th Department of Hepatic Surgery ,Molecular Oncology Laboratory , Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2012年第6期618-623,共6页
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
关键词 hepatocellular carcinoma HEPATECTOMY alpha-fetoprotein alpha-fetoprotein-L3
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Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice 被引量:21
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作者 Xing Wang Wang~1 Jin Hui Yuan~1 Ru Gang Zhang~1 Li Xia Guo~1 Yong Xie~2 Hong Xie~1 ~1Department of Biotherapy,Shanghai Institute of Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China ~2Department of Biology,Hong Kong University of Science and Technology,ChinaDr.Xing Wang Wang earned Ph.D.from Shanghai Institute of Materia Medical,Chinese Academy of Sciences in 1997.Now a professor at Shanghai Institute of Cell Biology,Chinese Academy of Sciences. 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期345-351,共7页
AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by i... AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction. 展开更多
关键词 Animals Apoptosis Carcinoma Hepatocellular Gene Expression Gene Therapy Humans In Vitro Liver Neoplasms Male MICE Mice Inbred BALB C Mice Nude Neoplasm Transplantation Oligodeoxyribonucleotides Antisense Research Support Non-U.S. Gov't Transplantation Heterologous Tumor Cells Cultured alpha-fetoproteinS
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Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation 被引量:21
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作者 Kohei Matsumoto Hiroya Ueyama +11 位作者 Kenshi Matsumoto Yoichi Akazawa Hiroyuki Komori Tsutomu Takeda Takashi Murakami Daisuke Asaoka Mariko Hojo Natsumi Tomita Akihito Nagahara Yoshiaki Kajiyama Takashi Yao Sumio Watanabe 《World Journal of Gastroenterology》 SCIE CAS 2016年第36期8203-8210,共8页
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
关键词 alpha-fetoprotein-producing GASTRIC CANCER GASTRIC CANCER with enteroblastic DIFFERENTIATION Early GASTRIC CANCER GLYPICAN 3 SALL4
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Using receiver operating characteristic curves to evaluate the diagnostic value of the combination of multislice spiral CT and alpha-fetoprotein levels for small hepatocellular carcinoma in cirrhotic patients 被引量:30
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作者 Guang-Sheng Jia Guang-Long Feng +5 位作者 Jin-Ping Li Hai-Long Xu Hui Wang Yi-Peng Cheng Lin-Lin Yan Hui-Jie Jiang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2017年第3期303-309,共7页
BACKGROUND: The various combination of multiphase enhancement multislice spiral CT (MSCT) makes the diagno- sis of a small hepatocellular carcinoma (sHCC) on the back- ground of liver cirrhosis possible. This stu... BACKGROUND: The various combination of multiphase enhancement multislice spiral CT (MSCT) makes the diagno- sis of a small hepatocellular carcinoma (sHCC) on the back- ground of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein (AFP) level ficiency for sHCC. could increase the diagnostic ef- METHODS: This study included 35 sHCC patients and 52 cir- rhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists em- ploying a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diag- nostic 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 sHCC on the background of liver cirrhosis. RESULTS: The area under ROC curve (AUC), sensitivity, and specificity of the combination of arterial phase+portal- venous phase+delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase+portal- venous 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 sHCC. CONCLUSIONS: The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for sHCC 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
关键词 hepatocellular carcinoma receiver operating characteristic multi-slice spiral CT alpha-fetoprotein delayed phase imaging
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Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma 被引量:19
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作者 Qiang Wang Qi Chen +6 位作者 Xia Zhang Xiao-Lan Lu Qin Du Tao Zhu Guo-Yuan Zhang Dong-Sheng Wang Qu-Ming Fan 《World Journal of Gastroenterology》 SCIE CAS 2019年第36期5515-5529,共15页
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
关键词 GAMMA-GLUTAMYLTRANSFERASE Aspartate aminotransferase PROTEIN induced by vitamin K ABSENCE or ANTAGONIST II alpha-fetoprotein Hepatitis B virus Hepatocellular carcinoma
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Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis 被引量:39
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作者 Hao Xing Yi-Jie Zheng +5 位作者 Jun Han Han Zhang Zhen-Li Li Wan-Yee Lau Feng Shen Tian Yang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2018年第6期487-495,共9页
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
关键词 Hepatocellular carcinoma Meta-analyses Protein induced by vitamin K absence or antagonist-Ⅱ alpha-fetoprotein
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Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection 被引量:13
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作者 Narongsak Rungsakulkij Wikran Suragul +3 位作者 Somkit Mingphruedhi Pongsatorn Tangtawee Paramin Muangkaew Suraida Aeesoa 《World Journal of Clinical Cases》 SCIE 2018年第6期110-120,共11页
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
关键词 Risk factors Prognosis alpha-fetoprotein HEPATOCELLULAR CARCINOMA Liver NEOPLASMS
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Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma 被引量:8
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作者 Sevil Uygun Ilikhan Muammer Bilici +6 位作者 Hatice Sahin Ayse Semra Demir Akca Murat Can Ibrahim Ilker Oz Berrak Guven M Cagatay Buyukuysal Yucel Ustundag 《World Journal of Gastroenterology》 SCIE CAS 2015年第22期6999-7007,共9页
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
关键词 alpha-fetoprotein HEPATOCELLULAR carcinoma PROLIDASE CIRRHOSIS MACROVASCULAR INVASION
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Alpha-fetoprotein specific CD4 and CD8 T cell responses in patients with hepatocellular carcinoma 被引量:9
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作者 Shahriar Behboudi Stephen P Pereira 《World Journal of Hepatology》 CAS 2010年第7期256-260,共5页
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
关键词 HEPATOCELLULAR carcinoma alpha-fetoprotein Cell-mediated IMMUNITY IMMUNOTHERAPY
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Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels 被引量:8
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作者 Wong Hoi She Albert Chi Yan Chan +2 位作者 Tan To Cheung Chung Mau Lo Kenneth Siu Ho Chok 《World Journal of Hepatology》 CAS 2018年第2期308-318,共11页
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
关键词 alpha-fetoprotein Liver TRANSPLANTATION RECURRENCE SURVIVAL
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miR-122-5p as a novel biomarker for alpha-fetoproteinproducing gastric cancer 被引量:8
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作者 Suguru Maruyama Shinji Furuya +10 位作者 Kensuke Shiraishi Hiroki Shimizu Hidenori Akaike Naohiro Hosomura Yoshihiko Kawaguchi Hidetake Amemiya Hiromichi Kawaida Makoto Sudo Shingo Inoue Hiroshi Kono Daisuke Ichikawa 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2018年第10期344-350,共7页
AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRN... AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC. 展开更多
关键词 GASTRIC CANCER alpha-fetoprotein alphafetoprotein producing GASTRIC CANCER MicroRNA miR-122-5p
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Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma 被引量:7
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作者 Kwang Il Kim Hye Kyung Chung +2 位作者 Ju Hui Park Yong Jin Lee Joo Hyun Kang 《World Journal of Gastroenterology》 SCIE CAS 2016年第27期6127-6134,共8页
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 pathogeni... 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&#x02019;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 tumor-specific reporter gene expression driven by an alpha-fetoprotein (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
关键词 alpha-fetoprotein Hepatocellular carcinoma Molecular imaging Reporter gene Tumor-specific enhancer/promoter
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Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study 被引量:4
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作者 Ping Xu Cheng-fu Xu +5 位作者 Xing-yong Wan Chao-hui yu Chao Shen Peng Chen Gen-yun Xu You-ming Li 《World Journal of Gastroenterology》 SCIE CAS 2014年第33期11865-11870,共6页
AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population.
关键词 Fatty liver alpha-fetoprotein ASSOCIATION OBESITY Risk factor
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