1.Long term outcomes of three-four-year-old offsprings of mothers with gestational diabetes mellitus
Geng SONG ; Lingying KONG ; Jing WANG ; Yilin SONG ; Huixia YANG
Chinese Journal of Perinatal Medicine 2013;(6):331-336
Objective To explore the long term effects of gestational diabetes mellitus (GDM)on offsprings of affected women.Methods One hundred and twenty-four singleton pregnant women with GDM,who delivered in Department of Obstetrics and Gynecology,Peking University First Hospital from June 14,2006 to December 31,2007,were enrolled as the study group.Ninety-eight singleton pregnant women with normal glucose metabolism who delivered at the corresponding period were enrolled as the control group.The follow-up study was performed from November 6,2010 to January 31,2011 on their offsprings.Anthropometry indexes,including height,weight,waist circumference,systolic and diastolic blood pressure (DBP),triceps skin fold (TSF) and sub-scapular skin fold (SSF) were measured.According to the development standard of children less than five years old issued by World Health Organization in 2006,there were six detailed evaluation indicators including length/height for age z-score (HAZ),weight for age z-score (WAZ),weight for length/ height z score (WHZ),body mass index (BMI) for age z-score (BAZ),triceps skin folds for agez-score (TSFZ) and sub-scapular skin folds for age z-score (SSFZ).Chi-square,t-test or variance analysis were applied.Results (1) No statistical difference on age,birth weight,sex,height,weight,BMI,waist circumference,blood pressure,TSF and SSF was found between offsprings of study and control group (P>0.05).(2) Offsprings in both groups were further divided into macrosomia and non-microsomia subgroups,i.e.GDM macrosomic subgroup (n =15),GDM nonmacrosomic subgroup (n=109),control macrosomia subgroup (n=6) and control non-macrosomia subgroup (n=92).Significant difference was shown amont the four subgroups in weight [(19.8±3.9),(17.0±1.9),(17.7±1.7)and (17.2±1.7) kg,F=6.238,P<0.001],BMI (17.6±2.6,16.0±1.2,16.6±1.1 and 16.2±1.1,F=5.901,P<0.001),waist circumference [(53.6±5.3),(49.9±2.7),(50.9±3.3) and (50.4±0.9) cm,F=5.307,P<0.001],WHZ (1.40±1.44,0.45±0.81,0.88±0.75 and 0,60±0.87,F=5.269,P=0.002),HAZ (1.22±0.78,0.47±0.82,0.98±0.74 and 0.50±1.00,F=3.668,P=0.013),WAZ (1.68±1.23,0.58±0.79,1.15±0.85and 0.71±0.93,F=7.361,P<0.001) and BAZ (1.41±1.52,0.42±0.84,0.81±0.76 and 0.60±0.90,F=5.210,P =0.002).While comparing between each two subgroups,there was statistical difference between GDM macrosomia subgroup and GDM non macrosomia subgroup,and between GDM marosomia subgroup and control non-macrosomia group.(3) While comparing GDM macrosomia and GDM non-macrosomia subgroup with control group [weight (17.2±2.5) kg,BMI (16.2± 1.4),waist circumference (50.5 ± 3.6) cm,DBP (55.2 ± 6.9)mm Hg,SSF(6.1 ± 1.8) mm,WHZ (0.62±0.87),HAZ (0.53±0.99),WAZ (0.73±0.92),BAZ(0.61±0.89)],the weight (F=9.283,P<0.001),BMI (F=8.707,P<0.001),waist circumference (F=7.934,P<0.001),DBP(F=3.123,P=0.046),SSF (F=3.499,P=0.032),WHZ (F=7.639,P<0.001),HAZ(F=4.709,P=0.010),WAZ (F=10.302,P<0.001) and BAZ (F=7.689,P<0.001) was higher in GDM group than the control group.(4) The proportions of overweight and obesity were higher in GDM macrosomia subgroup than in GDM non-macrosomia and control groups [overweight:9/15 vs24.8% (27/109) and 24.5% (24/98),x2 =8.870,P=0.012; obesity:5/15 vs 7.3%(8/109) and 9.2%(9/98),x2=10.083,P=0.006].If all subjects were divided into macrosomia and non-macrosomia group,then the proportion of overweight and obesity was higher in the former group [overweight:52.4% (11/21) vs24.4%(49/201),x2=7.560,P=0.006; obesity:28.6% (6/21)vs 7.9%(16/201),x2 =9.047,P=0.003].Conclusions GDM may have long term adverse effect on the development of offsprings at three-four-year-old with higher incidence of obesity or high diastolic blood pressure in macrosomic babies of GDM mothers than in non macrosomic babies of GDM mothers or babies of non GDM mothers.
2.The role of high mobility group protein 1 mediated the endoplasmic reticulum stress in cerebral ischemia/reperfusion injury
Jing ZHAO ; Wenjing GENG ; Bozhi ZHAI ; Yijun SONG
Chinese Critical Care Medicine 2016;28(4):364-368
Objective To explore the mechanism of high mobility group protein 1 (HMGB1) involved in endoplasmic reticulum stress (ERS) induced by brain ischemia/reperfusion (I/R),based on I/R-HMGB1-ERS as the breakthrough point.Methods The brain of rats birthed 1-3 days was harvested,and the brain cells were cultured in vitro,which were used in the experiment when the cells were in the third passage.The cells were divided into two groups:cells in blank control group were cultured under the normal conditions without any treatment,and the cells in hypoxia/reoxygenation group were cultured with 99.9% nitrogen for 60 minutes (hypoxia) followed by opening the bottle neck for reoxygenation 120 minutes to simulate I/R model.The HMGB1 gene was silenced by using small interfering RNA (siRNA,siRNA and transfection reagent Lipofectamine 2000 mixture gradient was transfected into the cultured cells) as HMGB1-siRNA transfection group,and blank control (without any treatment) and negative control group (transfected with control siRNA) served as controls.The mRNA and protein expressions of HMGB1 and ERS related molecules were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results ① In cells of hypoxia/reoxygenation group,the mRNA and protein expressions of HMGB1 and ESR related proteins,including glucose regulating protein 78 (GRP78),C/EBP homologous protein (CHOP) and caspase-12,were significantly higher than those of blank control group with statistical difference (the value in blank control group was served as baseline 1,HMGB1 mRNA:3.19±0.48 vs.1,t =2.183,P =0.008;GRP78 mRNA:2.07±0.33 vs.1,t =3.292,P =0.016;CHOP mRNA:1.93±0.28 vs.1,t =2.573,P =0.021;caspase-12 mRNA:2.42±0.42 vs.1,t =2.261,P =0.027:HMGB1 protein:2.28±0.36 vs.1,t =2.042,P =0.009;GRP78 protein:1.33±0.24 vs.1,t =2.781,P =0.016;CHOP protein:1.67±0.34 vs.1,t =2.174,P =0.021;easpase-12 protein:1.36±0.44 vs.1,t =3.192,P =0.008).It was indicated that ERS related molecules involved in cell hypoxia/reoxygenation process.2② After HMGB1 gene was silenced by siRNA,the cells after hypoxia/reoxygenation showed a decrease in the mRNA and protein expressions of HMGB1 and ERS related moleculars as compared with those of blank control group and negative control group (served the value in blank control group as baseline 1,HMGB1 mRNA:0.27±0.12 vs.1,1.02 ± 0.04;GRP78 mRNA:0.16 ± 0.13 vs.1,0.96 ± 0.04;CHOP mRNA:0.47 ± 0.09 vs.1,0.98 ± 0.07;caspase-12 mRNA:0.31 ±0.11 vs.1,1.05±0.02;HMGBI protein:0.23±0.04 vs.1,1.08±0.01;GRP78 protein:0.14±0.09 vs.1,1.35±0.03;CHOP protein:0.32±0.10 vs.1,0.93±0.06;caspase-12 protein:0.27±0.09 vs.1,0.97±0.08;P < 0.05 or P < 0.01).It was indicated that HMGB1 involved in ERS related with GPR7,CHOP,caspase-12.Conclusion Hypoxia/reoxygenation brain intracellular HMGB1 and ERS related molecules expression levels were significantly up-regulated,and silencing HMGB1 gene can significantly inhibit the expression levels of these molecules,and I/R-HMGB 1-ERS pathway may participate in the mechanism of brain I/R injury.
3.Effect on short and long term clinical outcome of attenuated plaque in patients with acute coronary syndrome ;after percutaneous coronary intervention
Xuebin GENG ; Li LI ; Hongling WANG ; Yuxin SONG ; Guoyu ZHAO ; Biqiong ZHAO ; Meirong TIAN ; Yi MA ; Jing YANG
Chinese Journal of Ultrasonography 2015;(6):492-495
Objective To explore the effect on prognosis of attenuated plaque (AP)in patients with acute coronary syndrome (ACS)after percutaneous coronary intervention(PCI).Methods This study was a prospective study which included 225 ACS patients who admitted to the cardiology and met the conditions between January 2009 and December 2011.Clinical data,intravascular ultrasound characteristics of plaque, blood flow in coronary angiography and cardiovascular complications within 30 days after PCI were recorded.The main form of follow-up was telephone follow-up,supplemented by patient follow-up and out-patient follow-up.Endpoint was major adverse cardiac events (MACE).Kaplan-Meier method was used to estimate survival rate.The survival difference between the two groups was compared using the Log-Rank test.Results Extravascular elastic membrane area (EEMA),plaque area (PA),plaque burden,remodeling index in AP group were significantly increased than those in non-AP group.Corrected TIMI frame count (CTFC)immediately after the balloon dilatation was significantly higher in AP group than in non-AP group. Recent overall complications were more frequently documented in AP group than in non-AP group,but long-term follow-up outcome of MACE-free survival curves showed no significant difference between the two groups.Conclusions Recent prognosis,not long-term prognosis,is affected by attenuated plaque in ACS patients after PCI,which help to stratify risk further and guide treatment in ACS patients.
4.Diversity of invasiveness and matrix metalloproteinases expression profile of human gastric carcinoma xenografted in different tissue environments.
Jing-shu GENG ; Hong-tao SONG ; Wu-ru WANG
Chinese Journal of Pathology 2004;33(1):53-56
OBJECTIVETo study the effect of tissue environment on the invasiveness of carcinoma cells and the implication of expression of matrix metalloproteinases.
METHODSTissue from a human gastric carcinoma was transplanted and passaged subcutaneously in nude mice. After the 3rd passage, the xenografts were also transplanted into the abdominal cavity of nude mice. The invasiveness of xenografts at the two locations were observed morphologically and the expressions of MMP-2, MMP-7, MMP-9, MMP-13, TM1-MMP, TM2-MMP and TM3-MMP were monitored by immunohistochemistry.
RESULTSThe subcutaneous xenografts of human gastric carcinoma in nude mice presented as expanding outgrowths with limited invasion. Except for MMP-7, the other 6 MMPs (MMP-2, MMP-9, MMP-13, TM1-MMP, TM2-MMP, TM3-MMP) were not expressed in the neoplastic cells nor in the tumor stroma. In contrast, the intra-peritoneal xenografts displayed an invasive growth pattern accompanied by more fibrous stroma. All MMPs examined were expressed in the tumor cells at the invasive fronts and in the adjacent stroma.
CONCLUSIONSInvasiveness and expression of MMPs were obviously diverse in human gastric carcinoma cells when grafted at different anatomic locations in nude mice, thus indicating: (1) There exists a close interaction between tumor cells and surrounding stromal cells. The tissue environment may play a definitive role in the tumor phenotype. (2) The expression of MMPs is closely related to the growth pattern and the invasiveness of tumor cells. MMPs produced by the stroma cells at the invasion front may be linked to the invasiveness of neoplastic cells.
Animals ; Cell Line, Tumor ; Humans ; Immunohistochemistry ; Matrix Metalloproteinases ; analysis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Stomach Neoplasms ; enzymology ; pathology ; Transplantation, Heterologous
5.Effect of montelukast combined with budesonide in the treatment of children with intermittent asthma
Gang CHEN ; Jing CAO ; Yurong GENG ; Qian LIU ; Xiaoli LIU ; Junhua SONG
Chinese Journal of Postgraduates of Medicine 2024;47(1):33-38
Objective:To analyze the effect of montelukast combined with budesonide in the treatment of children with intermittent asthma, and the impact on airway remodeling and T helper type 1 (Th1)/T helper type 2 (Th1/Th2) related cytokines.Methods:A prospective study was conducted among 120 children with intermittent asthma admitted to Huanghua Municipal People′s Hospital from December 2021 to February 2023. The children were randomly divided into the control group (60 children treated with budesonide atomizationinhalation) and the observation group (60 children treated with montelukast on the basis of the treatment of control group). Clinical efficacy, airway remodeling indicators [total area of airway (Ao), outer diameter of airway (D) and wall area to total airway cross-sectional area (WA%)], pulmonary function [peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV 1)/forced vital capacity (FVC) and the maximum expiratory flow at 25% of vital capacity (MEF25%)], Th1/Th2 related cytokines, inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6) and interferon-gamma (IFN-γ)], recurrence, and the incidence of adverse reactions were compared between the two groups. Results:The total effective rate in the observation group was higher than that in the control group: 90.00% (54/60) vs. 75.00% (45/60) ( P<0.05). After treatment, Ao, D and WA% in the observation group were lower than those in the control group: (17.58 ± 1.89) mm 2 vs. (19.22 ± 1.94) mm 2, (4.25 ± 0.48) mm vs. (4.48 ± 0.49) mm, (63.75 ± 6.49)% vs. (69.22 ± 7.14)% ( P<0.05). PEF, FEV 1/FVC and MEF25% in the observation group were higher than those in the control group: (3.13 ± 0.34) L/s vs. (2.86 ± 0.35) L/s, (87.45 ± 8.86) % vs. (83.59 ± 8.42) %, (87.63 ± 8.86)% vs. (82.15 ± 8.43)% ( P<0.05). The levels of Th1 and Th1/Th2 in the observation group were higher than those in the control group: (14.13 ± 1.46) % vs. (10.27 ± 1.25) %, 3.46 ± 0.39 vs. 1.88 ± 0.25, and the level of Th2 was lower than that in the control group: (3.96 ± 0.45)% vs. (5.48 ± 0.56)% ( P<0.05). After treatment, the levels of TNF-α and IFN-γ in the observation group were higher than those in the control group: (76.15 ± 7.78) ng/L vs. (66.38 ± 6.47) ng/L, (7.15 ± 0.74) ng/L vs. (6.14 ± 0.66) ng/L. The levels of IL-4 and IL-6 were lower than those in the control group: (77.85 ± 7.96) ng/L vs. (86.42 ± 8.74) ng/L, (37.25 ± 3.89) mg/L vs. (44.23 ± 4.57) mg/L ( P<0.05). The recurrence rate in the observation group was lower than that in the control group: 3.33% (2/60) vs. 15.00% (9/60) ( P<0.05). The incidence rates of adverse reactions in the two groups were without statistically significant difference between the groups ( P>0.05). Conclusions:Montelukast combined with budesonide can reduce airway remodeling in children with intermittent asthma, improve their pulmonary function, Th1/Th2 related cytokines and inflammatory response indicators, and reduce recurrence rate, with good safety.
6.Effect of all-trans retinoic acid on expressions of vascular endothelial growth factor and basic fibroblast growth factor in glioma stem cells
Yi-Jing LIU ; Yi-Quan KE ; Shi-Yong WANG ; Geng-Qiang LING ; Xin-Lin SUN ; Zhen-Hua SONG
Chinese Journal of Neuromedicine 2012;11(6):559-564
Objective To investigate the effect of all-trans retinoic acid (ATRA) on expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in glioma stem cells (GSCs). Methods GSCs were isolated from human glioblastoma cell line U87 and identified by detecting the expressions of CD133 and nestin with immunofluorescence staining. The obtained GSCs were divided into control group,empty vector group (cultured with dimethyl sulfoxide [DMSO]) and ATRA treatment group (cultured with 10 nmool/L ATRA).After 10 d of differentiation; the proliferation of the treated GSCs was evaluated using CCK8 assay; the expressions of glial fibrillary acidic protein (GFAP),β-tubulin Ⅲ and galactoeerebroside (GralC) in the cells were detected by immunofluorescence.VEGF and bFGF levels in cultured supernatant were measured by ELISA; the mRNA expressions of VEGF and bFGF were detected by RT-PCR. Results The target antibodies of neural stem cells (NSCs), CD133 and nestin,positively expressed in the GSCs; differentiated GSCs can differentiate several kinds of homologous daughter cells,which expressed the cell markers of astrocytes,neurons and oligodendrocytes: GFAP, β-tubulin LⅢ and GalC, respectively. The percentage of GFAP-positive differentiated GSC s in the ATRA treatment group was significantly higher as compared with that in the other 2 groups after 10 d of differentiation (P<0.05); the speed of proliferation of GSCs in ATRA treatment group was obviously slower than that in the other 2 groups 3-7 d after differentiation (P<0.05).The VEGF and bFGF levels and the mRNA expression levels of VEGF and bFGF in GSCs of the ATRA treatment group 24 h after differentiation were also significantly lower than those in the other 2 groups (P<0.05). Conclusion ATRA can induce the differentiation of GSCs and inhibit its proliferation.It may exerts its anti-glioblastoma effect through the VEGF and bFGF signaling pathways.
7.Treatment of acne vulgaris with auricular acupoint pricking-bloodletting plus auricular point sticking therapy: a randomized controlled study
Ya-Jing SONG ; Xi-Sheng FAN ; Meng-Yun LI ; Jie ZHANG ; Jing-Ran GENG ; Xiao LIANG ; Jun-Cha ZHANG ; Xiao-Qi ZHANG ; Shu-Bo ZHOU ; Nan WANG ; Jia-Xu ZHANG ; Xiao-Dan SONG ; Yan-Fen SHE ; Fu-Qing ZHANG
Journal of Acupuncture and Tuina Science 2019;17(3):196-202
Objective: To observe the clinical efficacy of auricular point pricking-bloodletting plus auricular point sticking therapy for acne vulgaris. Methods: A total of 66 patients with acne vulgaris were randomized into an observation group and a control group by the random number table, with 33 cases in each group. The observation group was treated with auricular point pricking-bloodletting plus auricular point sticking therapy, and the control group was treated only with auricular point sticking therapy. The treatments of both groups were performed twice a week, 4 weeks as a course of treatment, for 3 courses in total. The scores of skin lesions and dermatology life quality index (DLQI) scores were recorded before and after treatment to assess the clinical efficacy. Results: During the trial, there were 3 cases of drop-out both in the observation group and the control group. After 3 courses of treatment, the total effective rate of the observation group was 96.7%, while that of the control group was 76.7%. The difference between the two groups was statistically significant (P<0.05). The intra-group comparison showed that the scores of skin lesion and DLQI were both decreased with the increase of treatment times, that was, the scores were lower than those at the previous time point (allP<0.05). After 1, 2, and 3 courses of treatment, the scores of skin lesion and DLQI of both groups were statistically different from those of the same group before treatment (allP<0.05). At every time point during the treatment, the scores of skin lesion and DLQI of the observation group were lower than those of the control group, and the differences between the two groups were statistically significant (all P<0.05). Conclusion: Auricular point pricking-bloodletting plus auricular point sticking has a better curative effect than auricular point sticking therapy alone in the treatment of acne vulgaris, and has a time-effect correlation.
8.Biliary excretion characteristics of berberine, palmatine and jateorhizine in sandwich-cultured rat hepatocytes
Rui-Feng LIANG ; Xian-Mei SONG ; Wen-Jing GE ; Feng ZHANG ; Zhen DAI ; Ning LI ; Ping TIAN ; Geng-Sheng LI
Chinese Pharmacological Bulletin 2018;34(2):250-256
Aim To study the biliary excretion characteristics of berberine,palmatine and jateorhizine in rat hepatocytes.Methods Berberine,palmatine and jateorhizine were incubated with the sandwich-cultured rat hepatocytes (SCRH) in standard Ca2+ buffer or Ca2+ free buffer.The accumulation of the three compounds under different conditions were measured by UPLC-MS/MS.The biliary excretion index and biliary clearance were calculated,and the effect of P-gp or Mrp2 inhibitor on the transport of three compounds was also investigated.Results While the incubation time increased,the accumulation of the three compounds also increased.There were obvious differences in accumulation of berberine,palmatine and jateorhizine in incubations treated with standard buffer and calcium-free buffer.The P-gp inhibitors ciclosporin A and verapamil could inhibit the biliary excretion of berberine,palmatine and jateorhizine.However,the Mrp2 inhibitors MK571 and probenecid had no effect on biliary excretion of the three compounds.Conclusions The biliary excretion of berberine,palmatine and jateorhizine is mainly through an active process.They are all the P-gp substrates other than Mrp2 substrates.
9.Meta analysis of studies on epidemiology of hypertension in college and university teachers and staff
wei Xiao CHEN ; li Li SHI ; hao Jia LU ; lan Ya CHEN ; song Jing GENG ; Kui JIANG ; cheng Jian DONG
Chinese Journal of Medical Library and Information Science 2017;26(9):60-63
Objective To more effectively prevent hypertension and provide better health care for college and university teachers and staff by keeping abreast with the epidemiology of hypertension. Methods The data were extracted from the selected Chinese and English papers on epidemiology of hypertension, which was followed by a meta-analysis of the prevalence, awareness rate, cure rate, and control rate of hypertension in college and university teachers and staff of China. Results A total of 73 papers were included in this study. The total prevalence of hypertension was 23. 3% (95%CI=21. 1%-25. 6%), the prevalence of hypertension was 27. 2% (95%CI=24. 4%-30. 0%) in male hypertensive teachers and staff and was 18. 6% (95%CI=16. 6%-20. 6%) in female hypertensive teachers and staff. The prevalence of hypertension increased with the increasing age and tended to increase with the year of investigation in college and university teachers and staff of China, and was the lowest in East China followed by Central China and West China. The awareness rate, cure rate and control rate of hypertension were 68. 3% (95%CI=59 . 7%-76 . 8%) , 63 . 7% ( 95%CI=55 . 5%-71 . 9%) , and 37 . 7% ( 95%CI=28 . 0%-47 . 5%) respec-tively in college and university teachers and staff of China. Conclusion The prevalence of hypertension is different in college and university teachers and staff of China due to different sexes, ages and areas.
10.The effect of As2O3 on induction of apoptosis and inhibition of telomerase activity in colon cancer LS-174T cells.
Xi-Shan WANG ; Gui-Yu WANG ; Hai-Tao XU ; Kuan WANG ; Ming LIU ; Song-Bin FU ; Jing-Shu GENG ; Qi-Fan ZHANG ; Xin-Shu DONG ; Jia-Hong ZHAO
Chinese Journal of Oncology 2007;29(6):415-418
OBJECTIVETo study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma LS-174T cells and their activity of telomerase.
METHODSLS-174T cells and xenograft model of nude mice were treated with As2O3. The inhibitory effect of As2O3 on survival of LS-174T cells was determined by MTT assay. Apoptosis was determined by electron microscopy and fluorescence microscopy. Cell cycle was assessed by flow cytometry. Telomerase activity in LS-174T cells was determined by PCR-ELISA kit.
RESULTSWith the increasing concentration of As2O3, the ratio of living cells to dead cells decreased significantly, and the IC50 value was 5.23 micromol/L. Apoptosis curve appeared after 24 h and cells turned to apoptosis in a time-dependent manner. As2O3 inhibited the telomerase activity in cell extraction, obviously in a concentration-dependent and time-dependent manner. Inhibitiory effect of As2O3 on xenograft model of nude mice was observed by tumor volume and weight measurement, showing a significant difference between As2O3 and control groups (P < 0.05).
CONCLUSIONBoth the experiments in vitro and in vivo showed an inhibitory effect of As2O3 on colonrectal cancer S-174T cell growth, probably by induction of apoptosis and inhibition of telomerase activity.
Animals ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Colonic Neoplasms ; pathology ; prevention & control ; ultrastructure ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Microscopy, Fluorescence ; Oxides ; administration & dosage ; pharmacology ; Polymerase Chain Reaction ; methods ; Random Allocation ; Telomerase ; antagonists & inhibitors ; genetics ; metabolism ; Time Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays