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alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis:Preliminary experience

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Hepatobiliary & Pancreatic Diseases International 2020年第3期19卷 229-234页

作者： Zhe Yang Fang-Zhou Luo Shuo Wang Jan Lerut Li Zhuang Qi-Yong Li Xiao Xu Shu-Sen Zheng Department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhouChina Division of Hepatobiliary Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhouChina National Clinical Research Center of Infectious Diseases HangzhouChina Starzl Unit of Abdominal Transplantation University Hospitals Saint LucUniversitécatholique LouvainBrusselsBelgium

Background:Portal vein tumor thrombosis(PVTT)is regarded as a contraindication for liver transplantation(LT)in hepatocellular carcinoma(HCC).However,some of these patients may have a favorable prognosis after *** this study,we evaluated the biological behavior of HCC with PVTT using tumor biomarker(alpha-fetoprotein,AFP)and 18 F-FDG positron emission tomography(tumor standard uptake value)to identify a subset of patients who may be suitable for ***:Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were *** pre-transplant prognostic factors were identified by univariate and multivariate *** status was identified following Vp classification(Vp1-Vp4).Results:Three-year recurrence-free survival and overall survival rates were 40%and 65.4%in Vp2-Vp3 PVTT patients,21.4%and 30.6%in Vp4 PVTT patients(P8 cm,pretransplant AFP level>1000 ng/m L and intrahepatic tumor maximal standard uptake value(SUVmaxtumor>5)were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT *** risk patients were defined as total tumor diameter≤8 cm;or if total tumor diameter more than 8 cm,with both pre-transplant AFP level less than 1000 ng/m L and intrahepatic tumor SUVmax less than 5,***-two Vp2-3 PVTT HCC patients(46.8%)were identified as low risk patients,and their 3-year recurrence-free and overall survival rates were 67.6%and 95.2%,***:Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18 F-FDG SUVmax might be suitable for LT.

关键词： Hepatocellular carcinoma Liver transplantation Portal vein tumor thrombosis alpha-fetoprotein Standard uptake value

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alpha-fetoprotein,protein induced by vitamin K absence or antagonist-Ⅱ,lens culinaris agglutinin-reactive fraction of alpha-fetoprotein alone and in combination for early detection of hepatocellular carcinoma from nonalcoholic fatty liver disease:A multicenter analysis

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 559-568页

作者： Ming-Cheng Guan Wei Ouyang Si-Yu Liu Li-Yang Sun Wei-Yue Chen Xiang-Min Tong Hong Zhu Tian Yang Department of Medical Oncology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Laboratory Zhejiang University Lishui HospitalLishui 323000China Department of Hepatobiliary Pancreatic and Minimal Invasive SurgeryZhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014China The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province Department of Interventional RadiologyZhejiang University Lishui HospitalLishui 323000China School of Clinical Medicine Hangzhou Medical CollegeHangzhou 310059China Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Navy Medical University)Shanghai 200438China

Background:Current surveillance strategies for hepatocellular carcinoma(HCC)among patients with non-alcoholic fatty liver disease(NAFLD)are *** study aimed to investigate the diagnostic perfor-mance of alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and their combinations in HCC underlying NAFLD ***:Serologic AFP,AFP-L3,and PIVKA-Ⅱ levels in NAFLD patients with and without HCC were *** receiver operating characteristic(ROC)analyses,the area under the curve(AUC),sensitivity,and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their ***:This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD *** eleva-tion of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls(all P<0.001).When they were analyzed individually,PIVKA-Ⅱ showed the best performance in diagnosing any-stage HCC with an AUC of 0.869,followed by AFP(0.763;***-Ⅱ,P<0.001)and AFP-L3(0.689;***-II,P<0.001).When they were analyzed in combination,AFP+PIVKA-Ⅱ yielded the highest AUC(0.906),followed by AFP+PIVKA-II+AFP-L3(0.904;***+PIVKA-Ⅱ,P=0.086),PIVKA-Ⅱ+AFP-L3(0.881;***+PIVKA-II,P<0.001),and AFP+AFP-L3(0.759;***+PIVKA-II,P<0.001).Similar findings were obtained in the subgroup with early-stage NAFLD-HCC,as well as the non-cirrhotic ***:These data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD,and the combination of AFP+PIVKA-II signifi-cantly improved the diagnostic accuracy of NAFLD-HCC.

关键词： Hepatocellular carcinoma Nonalcoholic fatty liver disease alpha-fetoprotein Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence or antagonist-Ⅱ

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alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells

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World Journal of Gastroenterology 2005年第17期11卷 2564-2569页

作者： Meng-SenLi Qiu-LingMa QianChen Xin-HuaLiu Ping-FengLi Guo-GuangDu GangLi DepartmentofBiochemistry HalnanMedicalCollegeHalkou571101HalnanProvinceChina DepartmentofBiochemistryandMolecularBiology PekingUniversityHealthScienceCenterBeijing100083China

AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular ***: 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)***: 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 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.

关键词： alpha-fetoprotein Hepatocellular carcinoma Immune escape

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alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第32期11卷 5015-5018页

作者： Dénes Grg János Regly-Mérei Sándor Paku László Kopper Péter Nagy Department of Transplantation and SurgerySemmelweis University BudapestHungary Third Department of SurgerySemmelweis University BudapestHungary Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis UniversityBudapest Hungary First Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestHungary

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 nudear 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 on in vivo human tumors.

关键词： Hepatocellular carcinoma alpha-fetoprotein p53 β-catenin CD44

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alpha-fetoprotein-producing colon cancer with atypical bulky lymph node metastasis

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World Journal of Gastroenterology 2006年第47期12卷 7715-7716页

作者： Kuangi Fu Akihiro Kobayashi Norio Saito Yasushi Sano Shigeharu Kato Hiroaki Ikematsu Takahiro Fujimori Yasushi Kaji Shigeaki Yoshida Department of Radiology Dokkyo University School of Medicine 880 Kitakobaysashi Mibu Shimotuga Tochigi 321-0293 Japan Department of Gastrointestinal Oncology and Digestive Endoscopy National Cancer Center Hospital East Kashiwa Chiba 277-8577 Japan Department of Surgery National Cancer Center Hospital East Kashiwa Chiba 277-8577 Japan Department of Gastrointestinal Oncology and Digestive Endoscopy National Cancer Center Hospital East Kashiwa Chiba 277-8577 Japan Department of Surgical and Molecular Pathology Dokkyo University School of Medicine 880 Kitakobaysashi Mibu Shimotuga Tochigi 321-0293 Japan Department of Radiology Dokkyo University School of Medicine 880 Kitakobaysashi Mibu Shimotuga Tochigi 321-0293 Japan

alpha-fetoprotein (AFP)-producing colorectal cancer is extremely rarely reported until now. All of the reported cases harboring synchronous hematogenous spread including liver and/or lung metastasis had a poor prognosis and died within 12 mo. We here describe a 71-year old man with AFP-producing colon cancer who presented with an unusual bulky lymph node metastasis instead of hematogenous spread. He underwent adjuvant chemotherapy in addition to curative surgical resection, which prolonged his survival.

关键词： alpha-fetoprotein Colon cancer Bulky lymph node metastasis Computed tomography Colonoscopy

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alpha-fetoprotein-producing hepatoid adenocarcinoma of the lung responsive to sorafenib after multiline treatment:A case report

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World Journal of Clinical Cases 2022年第28期10卷 10236-10243页

作者： Su-Zhen Xu Xiao-Chen Zhang Qi Jiang Ming Chen Meng-Ye He Peng Shen Department of Medical Oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) ***,there is no standardized treatment strategy for advanced HAL and its prognosis is *** SUMMARY We report a 55-year-old man with unresectable AFP-related *** largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 *** patient’s serum AFP level was 9283 ng/m *** mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy,and serum AFP reached its highest level(71232.2 ng/m L).The patient was treated with sorafenib(400 mg twice daily,per os).Forty days later,the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/m *** patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response,as well as survival > 13 mo,which is among the longest reported for unresectable stage IV *** This is the first report to document successful treatment of unresectable AFPrelated HAL with single-agent sorafenib after multiline therapy.

关键词： Hepatoid adenocarcinoma Lung cancer alpha-fetoprotein Sorafenib Case report

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alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第27期22卷 6127-6134页

作者： Kwang Il Kim Hye Kyung Chung Ju Hui Park Yong Jin Lee Joo Hyun Kang Molecular Imaging Research Center Korea Institute of Radiological and Medical Sciences Korea Drug Development Platform using Radio-Isotope Korea Institute of Radiological and Medical Sciences

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 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.

关键词： alpha-fetoprotein Hepatocellular carcinoma Molecular imaging Reporter gene Tumor-specific enhancer/promoter

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Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma

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World Journal of Gastroenterology 2021年第28期27卷 4687-4696页

作者： Han Ah Lee Yoo Ra Lee Young-Sun Lee Young Kul Jung Ji Hoon Kim Hyunggin An Hyung Joon Yim Yoon Tae Jeen Jong Eun Yeon Kwan Soo Byun Yeon Seok Seo Department of Internal Medicine Korea University College of MedicineSeoul 02841South Korea Department of Biostatistics Korea University Anam HospitalSeoul 02841South Korea

BACKGROUND Diagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma(HCC)was not fully *** To evaluate the diagnostic accuracy of alpha-fetoprotein(AFP),the Lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and protein induced by vitamin K absence or antagonist-II(PIVKA-II)and their combination for HCC *** Patients with newly detected liver mass or elevated serum AFP levels were considered *** AFP level,AFP-L3 fraction,and PIVKA-II level were measured at the first *** In total,622 patients were included;355 patients(57.1%)had chronic liver disease,and 208(33.4%)had liver *** was diagnosed in 160 patients(25.7%).The area under the receiver operating characteristics curves(AUROCs)of the serum AFP,AFP-L3 fraction,AFP-L3,and PIVKA-II levels for the diagnosis of HCC were 0.775,0.792,0.814,and 0.834,respectively.A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation *** the binary regression analysis of the training cohort,the AFP,AFP-L3 fraction,and PIVKA-II(ALPs)score was calculated as follows:ALPs score=3.8×[serum AFP level(ng/mL)×AFP-L3 fraction(%)×0.01]+0.2×PIVKA-II level(mAU/mL).The AUROC of the ALPs score for diagnosis of HCC was 0.878,significantly higher than that of serum AFP level(P<0.001),AFP-L3 fraction(P<0.001),PIVKA-II level(P=0.036),and AFP-L3 level(P=0.006).The optimal ALPs score cut-off was 5.3(sensitivity,85.0%,specificity 80.1%).The validation cohort showed similar *** The ALPs score calculated using serum AFP level,AFP-L3 fraction,and PIVKA-II level showed improved accuracy in HCC diagnosis.

关键词： alpha-fetoprotein Lens culinaris agglutinin-reactive fraction of alphafetoprotein Protein induced by vitamin K absence or antagonist-II Hepatocellular carcinoma

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alpha-fetoprotein specific CD4 and CD8 T cell responses in patients with hepatocellular carcinoma

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World Journal of Hepatology 2010年第7期2卷 256-260页

作者： Shahriar Behboudi Stephen P Pereira UCL Institute of Hepatology University College LondonRoyal Free Hospitals

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.

关键词： Hepatocellular carcinoma alpha-fetoprotein Cell-mediated immunity Immunotherapy

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The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells

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Cell Research 2002年第2期12卷 151-156页

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 Department of Biochemistry and Molecular Biology Health Science Center Peking University Beijing China Department of Biophysics Health Science Center Peking University Beijing China

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× 10-8M (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

关键词： alpha-fetoprotein receptor signal transduction monoclonal antibody gene expression.

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