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Role of serum angiopoietin-2 level in screening for esophageal squamous cell cancer and its precursors

Chinese Medical Journal 2007年第14期120卷 1216-1219页

作者： ZHOU Ying-zhi FANG Xue-qiang LI Hao DIAO Yu-tao YANG Yan-fang ZHAO De-li WU Kan LI Hui-qing School of Public Health Shandong University Jinan 250012 China Qilu Hospital of Shandong University Jinan 250012 China Institute of Basic Medicine Shandong Academy of Medical Sciences Jinan 250062 China People＇s Hospital of Feicheng City Feicheng 271600 China

Background Angiopoietin-2 （Ang-2） is one of the critical regulators of tumor angiogenesis. Studies have shown a significant correlation of Ang-2 expression to tumor invasion and metastasis in various human cancers, but little is known about the serum Ang-2 （sAng-2） levels in esophageal squamous cell cancer （ESCC） and its precursors. In this study, we aimed to investigate its role in screening for ESCC and its precursors. Methods We carried out a free endoscopic screening in Feicheng City, a high ESCC incidence area in Shandong Province of China. serum samples were collected as follows： 91 from normal subjects, 44 from patients with esophagitis, 85 from patients with hyperplasia, and 13 from patients with early ESCC. In addition, 28 serum samples were obtained from patients with invasive ESCC undergoing surgery in People＇s Hospital of Feicheng City. All the subjects of the five groups were diagnosed by histopathology. The sang-2 levels were tested and compared, and the diagnostic power in early or/and invasive ESCC was calculated in terms of sensitivity and other parameters. Results The sAng-2 levels were （22.0±5.5）, （21.3±3.2）, （20.5±3.3）, （24.0±5.0）, and （29.8±5.0） U/ml in normal, esophagitis, hyperplasia, early ESCC, and invasive ESCC groups respectively. It was significantly higher in early ESCC than inhyperplasia group （P=-0.009）. The invasive ESCC group showed the highest Ang-2 level among all groups （all P=-0.000）. The sensitivities of sAng-2 to early and invasive ESCC were 23.1% and 78.6% respectively. Conclusion sang-2 level is related to carcinogenesis and progression of ESCC, but it can not be used to screen for early ESCC.

关键词： angiopoietin-2 esophageal neoplasms serum sensitivity diagnosis

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Interferon-c and interleukin-4 detected in serum and saliva from patients with oral lichen planus

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International Journal of Oral Science 2014年第1期6卷 22-26页

作者： Wen-Zhao Liu Ming-Jing He Long Long Dong-Liang Mu Ming-Shu Xu Xue Xing Xin Zeng Ga Liao Hong-Xia Dan Qian-Ming Chen College of Stomatology Chongqing Medical University Chongqing Research Center for Oral Diseases and Biomedical Science State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University

Our previous salivary study had demonstrated an apparent T helper 2 （Th2）-predominance in saliva of oral lichen planus （OLP） patients and suggested a potential of salivary interleukin-4 （IL-4） as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ （IFN-γ） and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP （40 of the erythematous/ulcerative form and 20 of the reticular form） were recruited for this study, with 40 age-sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine- predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.

关键词： oral lichen planus saliva serum T helper cytokines

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Predictive values of multidetector-row computed tomography combined with serum tumor biomarkers in preoperative lymph node metastasis of gastric cancer

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Chinese Journal of Cancer Research 2019年第3期31卷 453-462页

作者： Huihui Bai Jingyu Deng Nannan Zhang Huifang Liu Wenting He Jinyuan Liu Han Liang Department of Gastric Cancer Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin’s Clinical Research Center for Cancer

Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.

关键词： Gastric cancer MDCT serum tumor biomarkers preoperative

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Multiple cytokine profiling in serum for early detection of gastric cancer

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World Journal of Gastroenterology 2018年第21期24卷 2269-2278页

作者： Jian Li Liang Xu Zeng-Ci Run Wen Feng Wen Liu Peng-Jun Zhang Zhi Li Department of general surgery Affiliated Tumor Hospital of Zhengzhou University Department of Oncology General Hospital of Liaohe Oil Field Department of Pathology Affiliated Tumor Hospital of Zhengzhou University Department of Central Laboratory Affiliated Tumor Hospital of Zhengzhou University Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Interventional Therapy DepartmentPeking University Cancer Hospital & Institute

AIM To investigate the value of multiparameter joint analysis in the early diagnosis of gastric cancer(GC) in clinical practice.METHODS Concentrations of CEA, CA724 and three kinds of cytokines(TNF-α, IL-6 and IL-8) in 176 GC patients, 117 atypical hyperplasia patients, and 204 healthy control individuals were used for building the diagnostic model, then 58 GC patients, 41 atypical hyperplasia patients, and 66 healthy control individuals were enrolled independently. The joints of the indicators were analyzed by binary logistic regression analysis method.RESULTS For discriminating the healthy control group and the GC group, IL-6 had the best diagnostic value, and the area under curve(AUC) of joint analysis was 0.95(0.93-0.97). For the early stage and advanced stage GC, the AUC were 0.95(0.92-0.98) and 0.95(0.92-0.97). For discriminating the atypical hyperplasia group and GC group, CA724 had the best diagnostic value, and the AUC of joint analysis was 0.97(0.95-0.99). For the early stage and advanced stage GC groups, the AUC were 0.98(0.96-0.99) and 0.96(0.94-0.98). After evaluation, for discriminating the GC, early stage GC and advanced cancer group from the healthy control group, the diagnostic sensitivity was 89.66%, 84.21% and 92.31%, respectively, and the specificity was 92.42%, 90.91% and 90.91%. For discriminating the GC, early stage GC and advanced cancer groups from the atypical hyperplasia group, the diagnostic sensitivity was 87.93%, 78.95% and 92.31%, respectively, and the specificity was 87.80%, 85.37% and 90.24%.CONCLUSION We have built a diagnostic model including CEA, CA724, IL-6, IL-8, and TNF-α. It may provide potential assistance as a screening method for the early detection of GC.

关键词： Gastric cancer Atypical hyperplasia serum Cytokine Early detection

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Dynamic changes of serum protein in rats with acute intoxication of Chinese cobra snake venom by proteomic analysis

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Forensic Sciences Research 2020年第4期5卷 309-321页

作者： Hui Yan Ping Xiang Jingshuo Zhang Liqi Xie Min Shen Shanghai Key Laboratory of Forensic Science Shanghai Forensic PlatformDepartment of Forensic ToxicologyAcademy of Forensic ScienceShanghaiChina College of Pharmaceutical Sciences Soochow UniverstitySuzhouJiangsuChina Institutes of Biomedical Sciences Fudan UniversityShanghaiChina

To elucidate the toxic mechanism of snake venom at the protein level,proteomics technol-ogy was applied to investigate the effect of venom on circulation in the mammalian body.Temporal proteomic analysis was performed to profile the dynamic changes in the sera of Sprague-Dawley rats administered with Chinese cobra venom or saline.Using 8-plex iTRAQ analysis,392 and 636 serum proteins were identified to be linearly upregulated or downre-gulated over time in the low-dose group and high-dose group,respectively.These proteins were mainly associated with the acute phase response pathway,complement system,and liver X receptor(LXR)/retinoid X receptor(RXR)and farnesoid X receptor(FXR)/RXR activation pathways.Compared with the low-dose group,the immune response and integrin pathways were inhibited in the high-dose group,although no obvious effect was observed.With con-sistently higher or lower expression in the high-dose group compared to the low-dose group throughout the whole process of venom poisoning,two proteins,Kininogen-1(KNG1)and orosomucoid 1(ORM1),which are involved in metabolism and immune response,occu-pied a core position in the pathway network and are considered venom dose-dependent biomarker candidates.

关键词： Forensic sciences forensic toxicology proteomics snake bite cobra serum rats

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Diagnostic value of four serum exosome microRNAs panel for the detection of colorectal cancer

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 970-979页

作者： Lei Han Wen-Jie Shi Yi-Bin Xie Zhi-Guo Zhang Department of Oncology Beijing Daxing District People’s HospitalBeijing 102600China Department of Medicine Innovation Research Chinese PLA General HospitalBeijing 100853China Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100121China

BACKGROUND Early detection,early diagnosis,and early treatment are currently accepted methods that can effectively improve the efficacy of colorectal cancer(CRC)treatment.Exosomes were demonstrated to be potential tumor molecular markers.AIM To evaluate the diagnostic value of CRC by detecting four exosomal microRNAs(miRNAs)(miR-15b,miR-16,miR-21,and miR-31)that were demonstrated to have potential diagnostic value in serum.METHODS Relative expression levels of miR-15b,miR-16,miR-21,and miR-31 in 123 CRC,117 colorectal adenoma,and 150 healthy controls were detected,and single and panel models were evaluated.The 2-ΔΔCt method was used to calculate the relative expression of miRNA compared to the internal control(U6).Eighty-one CRC patients,67 colorectal adenoma patients,and 90 healthy controls were used for validation.RESULTS Compared to the healthy control group,the best indicator of the four miRNAs was miR-15b,and the sensitivity and specificity were 81.33%and 91.80%,respectively.For miR-15b,miR-21,and miR-31 individually,the sensitivity and specificity were 91.95%and 97.62%,95.06%and 94.44%,respectively.Compared to the colorectal adenoma group,miR-15b,miR-16,and miR-21 in the CRC group showed significant differences(P<0.05).The best single indicator was miR-16,with a sensitivity and specificity of 79.05%and 71.55%.The sensitivity and specificity of a panel that included miR-15b,miR-16,and miR-21 were 81.21%and 81.03%,and 85.19%and 82.09%,respectively,in the validation.CONCLUSION We built and validated a diagnostic model containing miR-15b,miR-21,and miR-31 expression levels to discriminate the healthy control group and CRC group,and its sensitivity and specificity were 95.06%and 94.44%,respectively.The miR-15b,miR-16,and miR-21 panel was used to discriminate the colorectal adenoma group and CRC group with a sensitivity and specificity of 85.19%and 82.09%,respectively.

关键词： Colorectal cancer Exosome serum miRNAs Biomarker

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Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第13期26卷 1463-1473页

作者： Satoyoshi Yamashita Akira Kato Toshitaka Akatsuka Takashi Sawada Tomohide Asai Noriyuki Koyama Kiwamu Okita Department of Gastroenterology and Hepatology Japan Community Health Care Organization Shimonoseki Medical CenterShimonosekiYamaguchi 7500061Japan Department of Physiology Faculty of MedicineSaitama Medical UniversityIruma-gunSaitama 3500495Japan Research and Development Division Sekisui Medical Company LimitedRyugasakiIbaraki 3010852Japan Clinical Research Department Eidia Company LimitedChiyoda-kuTokyo 1010032Japan Eisai Company Limited Shinjuku-kuTokyo 1600812Japan Department of Internal Medicine Shunan Memorial HospitalKudamatsuYamaguchi 7440033Japan

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)patients remains poor despite advances in treatment modalities and diagnosis.It is important to identify useful markers for the early detection of HCC in patients.Preneoplastic antigen(PNA),originally reported in a rat carcinogenesis model,is increased in the tissues and serum of HCC patients.AIM To determine the diagnostic value of PNA for discriminating HCC and to characterize PNA-positive HCC.METHODS Patients with hepatitis C virus(HCV)-related hepatic disorders were prospectively enrolled in this study,which included patients with hepatitis,with cirrhosis,and with HCC.A novel enzyme-linked immunosorbent assay was developed to measure serum PNA concentrations in patients.RESULTS serum PNA concentrations were measured in 89 controls and 141 patients with HCV infections(50 hepatitis,44 cirrhosis,and 47 HCC).Compared with control and non-HCC patients,PNA was increased in HCC.On receiver operating characteristic curve analysis,the sensitivity of PNA was similar to the HCC markers des-γ-carboxy-prothrombin(DCP)andα-fetoprotein(AFP),but the specificity of PNA was lower.There was no correlation between PNA and AFP and a significant but weak correlation between PNA and DCP in HCC patients.Importantly,the correlations with biochemical markers were completely different for PNA,AFP,and DCP;glutamyl transpeptidase was highly correlated with PNA,but not with AFP or DCP,and was significantly higher in PNA-high patients than in PNA-low patients with HCV-related HCC.CONCLUSION PNA may have the potential to diagnose a novel type of HCC in which glutamyl transpeptidase is positively expressed but AFP or DCP is weakly or negatively expressed.

关键词： serum preneoplastic antigen Hepatitis C virus Hepatocellular carcinoma Des-γ-carboxy-prothrombin α-Fetoprotein Sensitivity Specificity

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Highly accurate colorectal cancer prediction model based on Raman spectroscopy using patient serum

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World Journal of Gastrointestinal Oncology 2020年第11期12卷 1311-1324页

作者： Hiroaki Ito Naoyuki Uragami Tomokazu Miyazaki William Yang Kenji Issha Kai Matsuo Satoshi Kimura Yuji Arai Hiromasa Tokunaga Saiko Okada Machiko Kawamura Noboru Yokoyama Miki Kushima Haruhiro Inoue Takashi Fukagai Yumi Kamijo Digestive Disease Center Showa University Koto Toyosu HospitalTokyo 135-8577Japan Research Division JSR CorporationTokyo 105-0021Japan BaySpec Inc. San JoseCA 95131United States Fuji Technical Research Inc. Yokohama 220-6215Japan Department of Laboratory Medicine and Central Clinical Laboratory Showa University Northern Yokohama HospitalYokohama 224-8503Japan Department of Clinical Laboratory Showa University Koto Toyosu HospitalTokyo 135-8577Japan Department of Clinical Laboratory Showa University HospitalTokyo 142-8555JapanBML Inc.Tokyo 151-0051Japan Department of Hematology Saitama Cancer CenterInamachiSaitama 362-0806Japan Department of Pathology Showa University Koto Toyosu HospitalTokyo 135-8577Japan Department of Urology Showa University Koto Toyosu HospitalTokyo 135-8577Japan Showa University Koto Toyosu Hospital Tokyo 135-8577Japan

BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, bloodbased CRC screening technique based on Raman spectroscopy.METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC(12), rectal neuroendocrine tumor(2), colorectal adenoma(68), colorectal hyperplastic polyp(18), and others(84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R^2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R^2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.

关键词： Colorectal cancer Raman spectroscopy Machine learning Blood serum Diagnosis

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Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2019年第3期12卷 457-463页

作者： Yan-Yao Liu Yue Bin Xing Wang Hui Peng Department of Ophthalmology the First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology Chongqing Eye Institute

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. serum samples was obtained from the patients with exudative AMD and from the controls. serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, Pserum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, Pserum sCD146 level increases and may be a biomarker for exudative AMD.

关键词： age-related macular degeneration soluble CD146 vascular endothelial growth factor receptor 2 serum

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Correlation of hair risperidone concentration and serum level among patients with schizophrenia

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General Psychiatry 2019年第1期32卷 35-42页

作者： Xiujia Sun Lihua Wang Fuzhong Yang Juanjuan Ren Ping Jiang Hongmei Liu Huafang Li Chunbo Li Chen Zhang Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiaotong University School of MedicineShanghai200030China Shanghai Mental Health Center Shanghai Jiaotong University School of MedicineShanghai200030China

Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 pserum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statis

关键词： Correlation of hair risperidone concentration serum level among patients schizophrenia

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