Performance Evaluation and Clinical Usefulness of α-fetoprotein Test Measured on Sysmex HISCL-5000

Advances in the treatment of advanced hepatocellular carcinoma with ramucirumab / 医学研究生学报

Hepatocellular carcinoma（HCC）is one of the most common malignant tumors in the world with high morbidity and mortality. The onset of HCC is insidious and develops rapidly. and the vast majority of patients have progressed to the middle and late stages at the initial diagnosis, with poor prognosis. Sorafenib is the first molecular-targeted drug approved for first-line treatment of advanced HCC. Subsequently, a large number of clinical studies of molecular-targeted drugs have emerged and gradually applied in the clinic. Among them, ramucirumab has been studied a lot. At present, ramuizumab has been used in the second-line treatment of various malignant tumors, including gastric cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, etc. This paper reviews the anti-tumor mechanism, pharmacokinetics, toxicity, pharmacodynamics, relevant clinical trials in the treatment of advanced HCC.

Advances in the treatment of advanced hepatocellular carcinoma with ramucirumab / 医学研究生学报

Hepatocellular carcinoma（HCC）is one of the most common malignant tumors in the world with high morbidity and mortality. The onset of HCC is insidious and develops rapidly. and the vast majority of patients have progressed to the middle and late stages at the initial diagnosis, with poor prognosis. Sorafenib is the first molecular-targeted drug approved for first-line treatment of advanced HCC. Subsequently, a large number of clinical studies of molecular-targeted drugs have emerged and gradually applied in the clinic. Among them, ramucirumab has been studied a lot. At present, ramuizumab has been used in the second-line treatment of various malignant tumors, including gastric cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, etc. This paper reviews the anti-tumor mechanism, pharmacokinetics, toxicity, pharmacodynamics, relevant clinical trials in the treatment of advanced HCC.

Effect of transforming growth factor β signaling on the stem cell-mediated liver regeneration in mice after partial hepatectomy / 上海交通大学学报（医学版）

Objective • To explore the effect of inhibiting transforming growth factor β (TGF-β) signaling pathway on the stem cell-mediated liver regeneration in mice after partial hepatectomy (PH). Methods • Eighteen C57BL/6 male mice were selected to establish the model of hepatectomy. mRNA and protein levels of the signal molecules in TGF-β pathway, as well as stem cell markers α-fetoprotein (AFP) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in the liver tissues were detected before (PH0) and on the 1st (PH1), 3rd (PH3) and 7th (PH7) day after operation. Then, additional 32 mice were assigned into inhibitor group [PH+SB-431542, 10 mg/(kg•d)] and control group (PH+normal saline). The mice were sacrificed on the 1st (PH1) and 3rd (PH3) day after operation and liver remnants were obtained. Realtime-PCR, Western blotting, and immunofluorescence staining were used to detect the expressing variation of TGF-β signaling pathway, AFP and LGR5. Results • The mRNA and protein expression of TGF-β1, phosphorylated SMAD2 (p-SMAD2) protein, Afp mRNA, the number of AFP immune-positive cells and Lgr5 mRNA were upregulated significantly after PH, peaked at PH3 (P<0.05) and recovered to pre-operative level at PH7. Compared with control group, the above indices were all obviously inhibited in inhibitor group at PH3 (P<0.05). Conclusion • TGF-β signaling pathway may regulate the stem cell-mediated liver regeneration in mice after PH.

Challenges in the Management of a Child with Yolk Sac Tumour of the Nasal Cavity Presenting with Epistaxis and Progressive Respiratory Distress

@#Yolk Sac tumour (YST) of the nasal cavity is extremely rare with only less than five previously reported cases in the English literature. Due to its rarity, the diagnosis is not one that is considered at initial presentation until tissue biopsies are sent for histopathological examination. Serum α-fetoprotein levels aid in diagnosis and in monitoring progression of the tumour. Being a very uncommon tumour of germ cell origin presenting as localized disease in the nasal cavity, prognosis and survival rates are difficult to determine. We are reporting a rare yolk sac tumour case in an infant and the challenges encountered in its management.

A Highly Sensitive Sandwich Immunosensor for Determination of α-Fetoprotein / 分析化学

The Au-PDA-Fe3O4 decorated graphene oxide electrode was modified with Prussion blue-secondary antibodies for determination of cancer biomarker α-fetoprotein (AFP) with great sensitivity.Scanning electron microscopy (SEM), X-ray diffraction (XRD) and ultraviolet-visible absorption spectrometry were used to characterize the structure of the material.Greatly enhanced sensitivity for the cancer biomarker is based on a dual signal amplification strategy.First, Fe3O4-PDA-Au used for the biosensor platform increased the surface area to capture a large amount of primary antibodies (Ab1), which resulted in amplification of the detection response.Second, graphene oxide allowed several binding events of PB-Ab2.Enhanced sensitivity was also achieved by introducing the multibioconjugates of Ab2-PB-GO onto the electrode surface through sandwich immunoreactions.The test result shows that there are linear relationships between current and AFP concentrations ranging from 0.005 ng/mL to 1 ng/mL and 1 ng/mL to 20 ng/mL, with the low detection limit (LOD) of 1.0 pg/mL.This immunosensor is simple, low-cost and sensitive and shows a great potential in biomedicine, clinical diagnosis and health examination.

Expression of β-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein / 华中科技大学学报（医学）（英德文版）

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between β-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of β-catenin was predominant in HCC tissues. The abnormal expression of β-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of β-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased β-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of β-catenin, which may account for the poor prognosis of AFP-associated HCC patients.

The study of prognosis value of AFP and DNA ploidy detection in primary hepatic carcinoma / 国际检验医学杂志

Objective To investigate the relationship between the serum level of AFP ,types of DNA ploidy and 5 year survival rate ,survival time in patients with primary hepatic carcinoma (PHC) in Boluo area in Huizhou City ,and evaluate the prognosis val‐ue of these indexes in PHC .Methods 80 cases with PHC were enrolled in observation group and divided into grade I ,II ,III and IV according to pathological grading .Other 80 cases of healthy individuals ,conducted physical examination ,were enrolled in control group .Peripheral venous blood samples (2 mL) were collected from all subjects .The serum level of AFP and types of DNA ploidy were measured by electrochemiluminescence immunoassay (ECLIA) and flow cytometry ,respectively .Results The serum levels of AFP were significantly higher in patients in different pathological grade groups compared to that in the control group (P<0 .05) .In addition ,accompany increase of pathological grade ,the levels of AFP in patients with PHC were increased .The increased level of AFP ,difference of DNA ploid types and pathological grade of PHC contributed great influences on the 5 year survival rate and sur‐vival time of patients .Conclusion The serum level of AFP and the DNA heteroploid rate may play important roles in the early di‐agnosis and assessing prognosis of patients with PHC in Boluo area in Huizhou City .

Comparison of chemiluminescence enzyme immunoassay based on magnetic microparticles with traditional colorimetric ELISA for the detection of serum α-fetoprotein / 药物分析学报

A chemiluminescence enzyme immunoassay based on magnetic microparicles (MmPsCLEIA) was developed to evaluate serum α-fetoprotein (AFP) in parallel with tramional colorimetric enzyme-linked immunsorbrnt assay (ELISA).A sestematic comparison between the MmPs-CLEIA and colorimetric ELISA concluded that the MPs-CLEIA exhibited fewer of immunoreagents,less total assay time,and better linearity,recovery,precision,senitivity and validity.AFP was detected in forty human serum samples by the proposed MPs-CLEIA and ELISA,and the results werecompared with commercial electrochemilunminescence immunoassay (ECLIA) kit.The correlation coefficient between MPs-CLEIA and ELISA was obtained with R2=0.6703; however,the correlation between MPs-CLEIA and ECLIA (R2=0.9582) was obviously better than that between colorimetric ELISA and ECLIA (R2=0.6866).

Value of α-fetoprotein in predicting the curative effect of microwave ablation for hepatocellular carcinoma / 中华消化外科杂志

ObjectiveTo investigate the value of α-fetoprotein (AFP) in predicting the curative effects of microwave ablation for hepatocellular carcinoma (HCC).MethodsThe clinical data of 213 HCC patients who received microwave ablation at the Chinese PLA General Hospital from January 2005 to July 2010 were retrospectively analyzed.The AFP level was detected one week before treatment,and all the patients were divided into the AFP-negative ( AFP ＜ 20 μg/L) group (99 patients) and AFP-positive ( AFP ≥20 μg/L) group ( 114 patients).All patients were closely followed up until October 2010,and the clinicopathological data,survival estimates,complications and prognosis-relative factors were recorded.All data were analyzed by the t test,rank sum test,analysis of variance or Logistic regression analysis.The survival curve was drawn by the Kaplan-Meier method,and the survival was analyzed by the Log-rank test.ResultsThe 5-year local tumor progression rate,intrahepatic and extrahepatic metastasis were 5.5％,44.6％ and 9.9％,respectively.The 1-,2-,3-,4-,5-year accumulative survival rates were 95.6％,86.1％,77.3％,72.7％ and 67.5％,respectively.Eleven patients died in the AFP-negative group,and the 1-,3-,5-year accumulative survival rates were 97.8％,85.4％ and 74.6％,respectively.Twenty-three patients died in the AFP-positive group,and the 1-,3-,5-year accumulative survival rates were 93.9％,71.6％ and 61.3％,respectively.There was no significant difference in the survival between the 2 groups ( x2 =1.68,P ＞ 0.05 ).The results of univariate analysis showed that the preablation AFP level was associated with the complication rate,postablation intrahepatic metastasis and the survival ( Z =- 1.98,-3.46,- 1.92,P ＜ 0.05 ).The results of multivariate analysis showed that the preablation AFP level was associated with the gender,tumor diameter,hepatic cirrhosis and major complications (t =2.60,3.78,1.97,2.06,P ＜ 0.05 ).ConclusionHigher level of preablation AFP associates with poor prognosis after microwave ablation.

The diagnostic value of serum Golgi protein-73 in hepatocellular carcinoma / 肿瘤

Objective: To investigate the diagnostic value of serum Golgi protein-73 (GP73) in hepatocellular carcinoma (HCC). Methods: The peripheral serum samples from 504 individuals were collected, including 144 HCC patients, 50 cirrhotic patients, 100 hepatitis B patients, 84 hepatitis B virus carriers, 50 patients with other malignancies, 26 patients with benign liver tumor, and 50 healthy volunteers. The expression levels of serum GP73 and alpha-fetal protein (AFP) were detected by double antibody sandwich ELISA and electrochemiluminescence assay, respectvely. Results: The expression level of serum GP73 from the HCC patients was significantly higher than those from the other patient groups (P <0.05). When the cut-off value was determined as 64 ng/mL by the receiver operating characteristic (ROC) curve, the sensitivity and specificity of GP73 for the diagnosis of HCC were both higher than those of AFP (83.3% vs 72.2%; 88.3% vs 76.7%; both P <0.05). The sensitivity of GP73 in combination with serum AFP for the diagnosis of HCC was 94.4%. Conclusion: The sensitivity and specificity of serum GP73 for the diagnosis of HCC are higher than those of serum AFP. The rate of HCC diagnosis is increased by combined examination of serum GP73 and AFP. Copyright © 2012 by TUMOR.

Clinical features of hepatocellular carcinoma during pregnancy / 中华肝胆外科杂志

Objective To explore the clinical features of hepatocellular carcinoma (HCC) during pregnancy. Methods Clinical data of 4 patients with HCC in pregnancy were retrospectively analyzed.Results All 4 patients were positive for hepatitis B surface antigen. A marked increase in maternal serum a-fetoprotein (AFP) was found in 3 patients (310.1-5630.0 ng/ml ). Three patients were diagnosed at their advanced stages and died of disease in the 4th, 6th and 7th months, respectively. One patient diagnosed as having early HCC underwent curative surgery and has been without recurrence for 26 months. Conclusion The overall survival of patients with HCC in pregnancy is grim because most patients are diagnosed in the advanced stage. Surveillance with AFP and ultrasonography should be recommended for pregnant woman for the detection of early HCC, especially in hepatitis B virus carriers from high endemic areas, to improve patient survival.