1.Fumagillin inhibits colorectal cancer growth and metastasis in mice:an in vivo and in vitro study of antiangiogenesis
Xiaonan CUI ; Xinmiao LIANG ; Li HOU
China Oncology 2001;0(02):-
Background and purpose:Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation. However, its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated.In this study, the effect of Fumagillin on the growth of colon cancer was examined. Methods:Twenty mice were divided into 4 groups and injected subcutaneously with 5?105/L WiDr or HT-29 cells in 200 ?L phosphate-buffered saline (PBS) respectively. After 4 weeks, intraperitoneal injections of Fumagillin (0.1 mg/kg), Cyclo (1 mg/kg), or both were given every 2 days for 4 weeks. The tumor weight and microvessel density (MVD) were examined. Geneexpression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVECs). Results: The Fumagillin-treated mice showed smaller tumor mass and lower MVD-CD105 levels than control ones. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVECs showed up-regulation of 71 genes and down-regulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion and gene transcription. Quantitative real time-polymerase chain reaction and Western blot revealed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. Conclusion: Fumagillin was found to suppress colorectal cancer growth by suppressing angiogenesis. The down-regulation of cyclin E2, ALCAM and ICAM-1 by fumagillin may be involved in the anti-angiogenesis.
2.Fumagillin inhibits colorectal cancer growth and metastasis in mice: an in vivo and in vitro study of antiangiogenesis
Xiaonan CUI ; Xinmiao LIANG ; Li HOU
China Oncology 2010;20(2):86-94
Background and purpose: Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation. However, its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated.ln this study, the effect of Fumagillin on the growth of colon cancer was examined. Methods: Twenty mice were divided into 4 groups and injected subcutaneously with 5×10~5/L WiDr or HT-29 cells in 200 μL phosphate-buffered saline (PBS) respectively. After 4 weeks, intraperitoneal injections of Fumagillin (0.1 mg/kg), Cyclo (1 mg/kg), or both were given every 2 days for 4 weeks. The tumor weight and microvessel density (MVD) were examined. Gene-expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVECs). Results: The Fumagillin-treated mice showed smaller tumor mass and lower MVD-CD105 levels than control ones. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVECs showed up-regulation of 71 genes and down-regulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion and gene transcription. Quantitative real time-polymerase chain reaction and Westem blot revealed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. Conclusion: Fumagillin was found to suppress colorectal cancer growth by suppressing angiogenesis. The down-regulation of cyclin E2, ALCAM and ICAM-1 by fumagillin may be involved in the anti-angiogenesis.
3.The effect of cinobufacini injection on DNA topoisomerase Ⅰ of human hepatocellular carcinoma HepG-2 cells
Hua CHEN ; Yu SUN ; Xiaonan CUI
China Oncology 2010;20(3):197-201
Background and purpose:The cinobufacini injection is a traditional antitumor drug.However,its mechanism iS still unclear.The purpose of this study was to observe the effect of cinobufacini injections in DNA TOPO Ⅰ of human hepatocellular carcinoma HcpG-2 cells.Methods:The cells that were proliferated were assessed by MTT assay.Cell cycles were shown through FCM.TOPO Ⅰ mRNA expression was analyzed through RT-PCR.The activity of TOPO Ⅰ was measured by TOPO Ⅰ mediated super coiled PHR322 relaxation.Supercoiled PBR322 was also used to determine the direct DNA breakages.Results:Cinobufacini injections significantly inhibited HepG-2 cells proliferation in ways that were dependent on dosages and time.Induced tumor cells arrest at the S-phase.TOPO ⅠmRNA expression decreased in a manner that was dependent on dosages which inhibited the TOPO Ⅰ mediated DNA relaxations.However,the cinobufacini injections could not directly induce DNA breakage at any concentration.Conclusion:Cinobufacini injections can inhibit human hepatocellular carcinoma HepG-2 cells proliferation.The regulation of topoisomerase Ⅰ activity and mRNA expression may be one of the mechanisms that causes the cinobufacini injection to contribute against tumor.
4.Relationship between body composition and arterial function and its impacting factors
Xiaonan SUN ; Qiang ZENG ; Jing XIE ; Xu CUI
Chinese Journal of Health Management 2010;04(3):157-160
Objective To explore the relationship between body composition and arterial function index,especially augmentation index(AI),and make clear the impacts of gender and age on the relationship.Methotis A total of 3859 health adults were enrolled in this study.Boay composition was measured by bioelectrical impedance,and AI and pulse wave velocity(PWV) were viewed as indictors for arterial function.Correlation analysis and liner regression analysis were used for data comparison.Results Both body mass index(BMI) and body fat rate positively changed with PWV(r=0.114,both P<0.01).However,BMI showed no relation to AI(r=0.022,P>0.05).Body fat rate was positively and independently associated with AI(r=0.263, P<0.01),which was gender-dependent(female:r=0.219,P<0.01;male:r=0.033,P>0.05).When age was concerned,above relationship was more stronger in participants ≤50 years(β=0.479 vs β=0.321,P<0.01).Conclusion Body fat mass may be a predicting factor of changes in AI.Gender and age could affect the relationship between body fat and rtery function.
5.Relation between lipid fluctuations of daily diet and insulin resistance in patients with type 2 diabetes mellitus with normal fasting lipid profile
Lijuan CUI ; Ling MA ; Yu HAN ; Liwei HUANG ; Yunhua YANG ; Xiaonan ZHANG ; Jing XU
Clinical Medicine of China 2016;32(7):615-618
Objective To investigate the relationship between lipid fluctuations of daily diet and insulin resistance in patients with type 2 diabetes mellitus(T2DM) with normal fasting lipid profile. Methods One hundred and ninety?eight cases patients with T2DM who were treated in the Endocrinology Department of the General Hospital of Benxi Iron and Steel Group Corporation from October 2012 to September 2014 were selected. Patients were divided into three groups according to fasting and postprandial 4 h triglyceride( TG4 h)
level,the group with normal fasting TG and normal TG4 h with 38 cases,the group with normal fasting TG and rising TG4 h with 78 cases,the group with rising fasting TG and rising TG4 h with 82 cases. The control group was composed of healthy volunteers with 20 cases. The patients followed daily diet habits to eat,blood glucose, insulin and lipid level of fasting and 2 h,4 h after lunch were monitored. Homeostasis model insulin resistance index( HOMA?IR) was used as an index to evaluate insulin resistance,and the correlation analysis was carried out with fasting and dietary intake of postprandial lipid metabolism. Results (1)HbA1c,FPG,HOMA?IR,TG and insulin level in the patients of the group with normal fasting TG and normal TG4 h,the group with normal fasting TG and rising TG4 h,the group with rising fasting TG and rising TG4 h were higher than the control group (HbA1c:(8. 4±1. 9)%,(8. 2±2. 4)%,(7. 8±1. 8)% vs. (4. 3±0. 6)%);FPG:(8. 98±1. 93) mmol/L, (8. 62±1. 33) mmol/L,(8. 28±1. 26) mmol/L vs. (4. 82±0. 63) mmol/L;,HOMA?IR:11. 07±0. 11,6. 98 ±0. 08,3. 83±0. 09 vs. 1. 24±0. 16;TG:0 h TG:(2. 35±1. 85) mmol/L,(1. 60±0. 41) mmol/L,(1. 58±0. 46) mmol/L vs. (0. 82±0. 25) mmol/L;2 h TG:(3. 97±2. 96) mmol/L,(2. 98±1. 49) mmol/L,(1. 83±0. 62) mmol/L vs. (1. 22±0. 31) mmol/L;4 h TG:(4. 24±1. 57) mmol/L,(3. 15±1. 63) mmol/L,(1. 92±0. 53) mmol/L vs. (1. 16±0. 24) mmol/L;insulin(0 h insulin:(26. 51±3. 65) mU/L,(18. 18±6. 24) mU/L,(10. 31 ±2. 38) mU/L vs. (5. 87±1. 62) mU/L;2 h insulin:(59. 15±8. 34) mU/L,(43. 75±9. 83) mU/L,(34. 27 ±1. 61) mU/L vs. (25. 24±1. 98) mU/L;4 h insulin:(51. 22±6. 79) mU/L,(40. 06±7. 51) mU/L,(31. 06 ±1.77) mU/L vs. (13.36±1.37) mU/L;P<0.05). (2)WHR(0.90±0.08 vs.0.72±0.06),HOMA?IR, insulin level of fasting and 2 h,4 h after lunch,TG of 2 h,4 h after lunch in the group with normal fasting TG and rising TG4 h were higher than the group with normal fasting TG and normal TG4 h ( P<0. 05 ) . ( 3 ) BMI ((27. 3±3. 3) kg/m2 vs. (23. 1±1. 5) kg/m2),WHR(0. 96±0. 10 vs. 0. 72±0. 06),HOMA?IR,TG and insulin level of fasting and 2 h,4 h after lunch in the group with rising fasting TG and rising TG4 h were higher than the group with normal fasting TG and normal TG4 h( P<0. 05) . HOMA?IR,TG and insulin level of fasting and 2 h, 4 h after lunch in the group with rising fasting TG and rising TG4 h were higher than the group with normal fasting TG and rising TG4 h( P<0. 05) . ( 4) HOMA?IR was positively correlated with BMI,WHR,and fasting TG levels in the groups with diabetes(r=0. 297,0. 376,0. 326,P<0. 05). HOMA?IR was significantly positively correlated with TG of 2 h,4 h after lunch in the groups with diabetes( r=0. 529,0. 693,P<0. 05) . HOMA?IR was significantly positively correlated with BMI and WHR in the control group(r=0. 617,0. 728,P <0. 05). HOMA?IR was not significantly correlated with fasting and postprandial TG in the control group. Conclusion Postprandial lipid metabolism disorder after daily diet is in some of patients with T2DM with normal fasting lipid profile. Postprandial lipid metabolism disorder after daily diet is significantly positively correlated with insulin resistance in patients with T2DM. Insulin resistance may be one of the pathogenesis of postprandial dyslipidemia in patients with type 2 diabetes.
6.HCC serum associated proteins screened by SELDI-TOF-MS analysis
Jiefeng CUI ; Rong YANG ; Yinkun LIU ; Xiaonan KANG ; Cheng HUANG ; Ruixia SUN ; Yang LI
Chinese Journal of Laboratory Medicine 2010;33(3):213-218
Objective To screen potential serum HCC associated proteins with low molecular weight and low abundance for better understanding the pathological mechanism of HCC and discovering new biomarkers.Methods All serum samples were collected from 81 HBV-related HCC patients,43 chronic hepatitis B patients and 36 cirrhosis patients.Serum protein fingerprint profiles were first generated by selected WCX2 protein chip integrating with SELDI-TOF-MS,and then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard.Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra was performed.Some protein peaks with significant difference among HCC,cirrhosis and chronic hepatitis B groups were found.The reproducibility of the SELDI system was assessed before serum protein fingerprint profiles analysis.Results The intra-and inter-assay CV for intensity and m/z in this SELDI system were 17.46% and 0.024%,and 17.74% and 0.024% respectively.Total 128 protein fingerprint peaks between 2 000 to 30 000 Da were identified under the condition of signal to noise>5 and minimum threshold for cluster>20%.Eighty-seven proteins were found to significantly expressed between HCC and cirrhosis groups(P<0.05).Of the above differential proteins,forty-five proteins had changes greater than two fold,including 15 up-regulated proteins and 30 downregulated proteins in HCC sera.Between HCC and chronic hepatitis B groups,nine of fifty-two differential proteins(P<0.05) had intensities of more than two folds,including 2 up-regulated proteins and 7 downregulated proteins in HCC sera.Between cirrhosis and chronic hepatitis B groups,twenty-eight of seventynine significantly differential proteins(P<0.05) changed greater than two folds in intensity,including 17 up-regulated proteins in cirrhosis seru and 11 down-regulated proteins in chronic hepatitis B sera.Analysis of above leading differential proteins among three diseases using subtraction difference mode,the 5 common down-regulated proteins 2 870,3 941,2 688,3 165 and 5 483 m/z in HCC sera and 2 common up-regulated proteins 3 588 and 2 017 m/z in cirrhosis and HCC sera were screened.But no statistic difference in the level of protein 2 017m/z was found between HCC group and normal group inour previous study.Conclusion Because the interference of unspecific proteins from hepatitis B and cirrhosis could be eliminated partly in HCC sera through subtraction difference analysis,these 6 common differential proteins (2 870,3 941,2 688,3 165,5 483,3 588 m/z)have obvious advantages of increased specificity for evaluating the pathological state of HCC and might become promising candidate biomarkers in the diagnosis of HCC.
7.Establishment of biology reference interval of NSE in cerebrospinal fluid
Yanfei CAO ; Gang CHEN ; Lina ZHANG ; Xiupeng DONG ; Xiaonan KOU ; Ying CUI ; Xiuhua CAO
International Journal of Laboratory Medicine 2015;(10):1321-1322,1324
Objective To establish the reference intervals of neuron specific enolase (NSE) in tumor markers in cerebrospinal fluid .Methods According to National Committee for Clinical Laboratory Standards document C 28‐A2 ,120 samples were collected to establish reference intervals .Then ,the established intervals were evaluated according to China National Accreditation Service for Conformity Assessment document CL38 :2012 .Results The biological reference interval of NSE in cerebrospinal fluid was 0-3 .14 ng/mL .There was no significant correlation between cerebrospinal fluid NSE level and age ,sex (P> 0 .05) .Conclusion Method used in this study could be ensured reliable ,accurate ,scientific and practical ,desirable for clinical requirement and with great poten‐tial for clinical application .
8.Effect of Roux-en-Y gastric gastrointestinal bypass surgery on islet function of patients with type-2 diabetes mellitus pancreatic
Haibin CUI ; Dongxia FU ; Xiyong BAI ; Huaie GE ; Wei ZHANG ; Xiaonan WEI
Clinical Medicine of China 2014;30(1):79-81
Objective To investigate the effect of gastrointestinal Roux-en-Y gastric bypass surgery on blood sugar and insulin function of patients with type-2 diabetes mellitus.Methods Twenty-seven cases of gastric cancer patients with type-2 diabetes and undergone Roux-en-Y bypass the gastrointestinal treatment in the centre hospital of Cangzhou were selected as our subject.Body mass index (BMI),Glycosylated hemoglobin (HBA1c),Fasting and glucose (FPG),fasting insulin (FINS),Fasting C-peptide (FCP) levels were measured.Glucose (2 hPG),insulin (2 hINS) and C-peptide (2 hCP) levels were detected after 2 h for oral use 75 g glucose.Homeostasis model was applied to assess insulin resistance index (HOMA-IR).Results No significant change was seen in terms of BMI between before and after surgery.Compared to before surgery,the levels of FPG((7.58 ±0.84) mmol/L),2 hPG((10.43 ± 1.88) mmol/L),HbA1c((7.56 ± 1.15)%) and HOMA-IR(4.55 ±0.76) were lower in patients at 3 months after surgery ((9.93 ± 1.57) mtmol/L,(13.89± 2.13) mtmol/L,(9.88 ± 1.66) %,(4.55 ± 0.76),respectively,P < 0.05 or P < 0.01).FPG ((6.56± 0.80) mmol/L),2 hPG ((8.57 ± 1.32) mmol/L),HbA1 c ((6.37 ± 1.24) %),HOMA-IR (4.03 ± 0.45)of patients after 6 months were lower than that of before surgery and 3 months after surgery (P < 0.05 or P<0.01).However,the levels of FINS ((13.67 ± 1.96) mU/L),FCP((2.62 ±0.87) μg/L),2 hINS((49.91± 5.14) mU/L) and 2 hCP ((6.28 ± 1.65) μg/L) were higher in patients with 3 months after surgery compared to that of before surgery ((11.08 ± 1.69) mU/L,(1.78 ± 0.61) μg/L,(36.05 ± 4.03) mU/L,(4.28 ± 1.48) μg/L,P < 0.01).Meanwhile those indices after 6 months (FINS:(15.88 ± 2.05) mU/L,FCP:(3.30 ±0.68) μg/L,2 hINS:(67.40 ±5.68) mU/L,2 hCP:(9.39 ± 1.52) μg/L) were higher than that of before surgery and 3 months after surgery(P < 0.01).Conclusion Roux-en-Y gastrointestinal bypass can effectively reduce blood sugar level and improve the situation of Pancreatic Beta-cell function of gastric cancer patients with type-2 diabetes.
9.Adenoid cystic carcinoma of the tracheobronchial tree:MSCT features
Xiaoyan MENG ; Zhaoxiang YE ; Xubin LI ; Juxiang MA ; Hongren WANG ; Xiaonan CUI
Chinese Journal of Clinical Oncology 2014;(5):328-331
Objective:This study is to improves the understanding of adenoid cystic carcinoma (ACC) of the tracheobronchial tree by observing the multi-slice cornputed tomography (MSCT) features. Methods:The MSCT features of 19 cases with primary tra-cheobronchial ACC confirmed by histopathology were retrospectively analyzed. Results:Among the 19 cases, lesions were located in the trachea in seven cases, in the segmental and above segmental bronchi in 10 cases, in the peripheral lung in two cases. Intra-and ex-traluminal growth were observed in 15 cases (79%), whereas broad-based intraluminal lesions were exhibited in two cases (11%). Among the seven cases of tracheal ACC, the CT scans for five cases showed a notable tendency toward submucosal extension. Two cas-es manifested as a diffuse or circumferential wall thickening of the trachea, and the other three cases presented homogeneous mass fill-ing of the trachea with wall thickening. The 10 cases with bronchial ACC were manifested as intra-and extraluminal growth. Eight cas-es presented homogeneous polypoid growth toward the adjacent lumen, and seven cases presented extraluminal parts that were larger than the intraluminal parts. Among 13 contrast-enhanced examinations, three cases were without enhancement, five cases were slightly enhanced, four cases were moderately enhanced, and one case was highly enhanced. Conclusion:MSCT performances of ACC of the tracheo-bronchial tree possessed certain characteristics, such as broad-based mass, intra- and extraluminal growth, and diffuse wall thickening. CT can diagnose tumor malignancy, but the definitive diagnosis for ACC should depend on pathology.
10.Clinical value of multislice spiral computed tomography examination on risk assessment of gastrointestinal stromal tumor
Juxiang MA ; Zhaoxiang YE ; Xubin LI ; Houli LUO ; Xiaonan CUI ; Hongren WANG
Chinese Journal of Digestive Surgery 2015;14(3):242-247
Objective To summarize the features of multislice spiral computed tomography (MSCT) examination of gastrointestinal stromal tumors (GISTs),and investigate the relationship between predictors and risk of MSCT examination for GISTs.Methods The clinical data of 110 patients with GISTs who were admitted to the Tianjin Medical University Cancer Institute and Hospital from July 2011 to February 2014 were retrospectively analyzed.All the patients received 64-slices spiral CT (64S-SCT) or 16-slices spiral CT (16S-SCT) scan,and the data were transported to the PACS work station for multiplanar reconstruction.All the tumor samples were collected during operation and diagnosed by morphological manifestation and immunohistochemistry of tumors.Very low,low,and medium risk of GISTs were regarded as lower risk grade,and high risk of GISTs as high risk grade.The univariate analysis and multivariate analysis about features of imaging and risk were done by chi-square test and multivariate logistic regression model.Results Tumors located at the stomach in 81 cases,small intestines in 26 cases and colorectum in 3 cases.Diameter of tumors was 0.8-25.0 cm.Smaller tumors were in round or oval shape with well demarcated boundary,and larger tumors were irregular with unclear boundary.Endo-luminal growth of lessions was detected in 25 cases,duplex growth in 35 cases and extra-luminal growth in 50 cases.Enhanced CT scan showed that most of tumors in 105 patients demostrated moderate and high enhancement,heterogeneous enhancement in 74 cases,low density sacvariable necrosis area without enhancement in 60 cases and superficial,cracked-like and deep ulcer without calcification,metastasis and ascites in 23 cases.According to the features of GISTs by MSCT examination,location of tumor,diameter,shape,boundary,growth,enhancement,cystic necrosis,ulcer and metastasis were risk factors affecting risk classification of tumors by univariate analysis (x2=7.442,49.966,31.513,46.038,13.836,16.626,23.489,8.280,6.811,P <0.05).Diameter of tumor more than 10 cm and ulcer were independent risk factors affecting risk classification of tumors by multivariate analysis (OR =9.927,0.070 ; 95% confidence intewal:1.888-52.180,0.012-0.398,P < 0.05).Conclusion There is a characterization in the location,diameter,shape,boundary of tumor,growth,enhancement,cystic necrosis,ulcer and metastasis,and diameter of tumor more than 10cm and ulcer are independent risk factors affecting the risk classification of GISTs.