5-烯丙基-7-二氟亚甲基白杨素对人卵巢癌裸鼠移植瘤生长的影响

目的:研究5-烯丙基-7-二氟亚甲基白杨素(ADFMChR)对人卵巢癌COC1裸鼠移植瘤生长的影响。方法:建立人卵巢癌COC1裸鼠皮下移植瘤模型,随机分为5组:生理盐水组、顺铂组(2mg/kg)、低剂量ADFMChR组(6mg/kg)、中剂量ADFMChR组(18mg/kg)和高剂量ADFMChR组(54mg/kg),每组4只。观察各组裸鼠移植瘤生长情况,裸鼠体重的变化,检测裸鼠血清谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、肌酐(CRE)及外周血白细胞计数;PI染色流式细胞术(FCM)测定移植瘤细胞凋亡率。结果:ADFM-ChR有明显抑制移植瘤生长的作用,低剂量组、中剂量组和高剂量组的瘤重抑制率分别为42.86%,62.76%和77.55%。ADFMChR3种剂量组处理裸鼠的外周血白细胞数和血清谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、肌酐(CRE)与生理盐水对照组的差异均无统计学意义(P>0.05)。PI流式细胞术结果显示ADFMChR诱导移植瘤细胞凋亡,呈剂量依赖性。结论:ADFMChR通过诱导细胞凋亡抑制人卵巢癌裸鼠移植瘤的生长。     

GE7导入系统介导抑癌基因NOEY2体内导入治疗人上皮性卵巢癌裸鼠网膜移植瘤的研究

目的 :研究GE7导入系统体内导入效率及介导抑癌基因NOEY2体内导入后对人上皮性卵巢癌裸鼠网膜移植瘤的治疗作用。方法 :将人上皮性卵巢癌细胞株Hey细胞种植于裸鼠皮下成瘤后半包埋缝于裸鼠脾区网膜建立网膜移植瘤模型。将GE7- β -gal四元复合体经腹腔注入荷瘤鼠体内用X -gal染色法检测基因导入效率 ,同法导入生理盐水、GE7-pcDNA3四元复合体及GE7-pcDNA3-NOEY2四元复合体 ,研究其抑制肿瘤生长的作用。结果 :人上皮性卵巢癌裸鼠网膜移植瘤的成瘤率达 10 0 % ,3周后瘤体达 3 68± 0 82g。GE7- β -gal四元复合体经腹腔注入荷瘤鼠体内 12h后 β -gal即有表达 ,4 8h后以瘤体、肝、脾表达率最高。GE7-pcDNA3-NOEY2四元复合体腹腔注射 3周后瘤体生长抑制率为 4 0 81% (P <0 0 5)。结论 :人上皮性卵巢癌裸鼠网膜移植瘤模型具有实用性。GE7导入系统体内导入基因效率高 ,具有相对肿瘤靶向性。GE7导入系统介导抑癌基因NOEY2体内导入后能有效抑制上皮性卵巢癌的生长。     

米非司酮对卵巢上皮性癌耐药细胞DNA修复基因表达和顺铂敏感性的影响

目的 研究米非司酮对卵巢上皮性癌(卵巢癌)耐药细胞DNA修复基因表达的调控,及对顺铂的增敏作用.方法 应用四甲基偶氮唑蓝比色法检测2.5、5.0、10.0 μmol/L米非司酮作用后卵巢癌顺铂耐药细胞株COC1/DDP的顺铂半数抑制浓度(IC50);用RT-PCR技术、流式细胞仪检测米非司酮联合顺铂作用后COC1/DDP细胞ERCC1、BRCA1、hMLH1 mRNA的表达水平及细胞周期和凋亡率的变化;建立COC1/DDP细胞裸鼠皮下移植瘤模型,分为顺铂组、米非司酮组、联合组和对照组,观察米非司酮在裸鼠体内对顺铂的增敏作用.结果 2.5、5.0、10.0 μmol/L米非司酮分别使COC1/DDP细胞对顺铂的IC50下降为(3.18±0.46)、(1.95±0.14)和(0.64±0.18)μg/ml,2.5 μmol/L米非司酮联合顺铂作用后的IC50与单用顺铂者[(3.71±0.38)μg/ml]比较,差异无统计学意义(P=0.076),其他浓度之间两两比较,差异均有统计学意义(P＜0.01).米非司酮下调ERCC1、BRCA1、hMLH1 mRNA表达水平,3种基因mRNA的相对表达量随米非司酮浓度的升高均呈下降趋势.2.5、5.0、10.0 μmol/L米非司酮联合顺铂对COC1/DDP细胞作用后,G0/G1,期细胞比例升高(分别为51.68%、53.74%、55.08%).2.5、5.0、10.0 μmol/L米非司酮与10 μg/ml顺铂联合作用使细胞凋亡率分别增加为5.11%、9.13%和12.24%.米非司酮联合顺铂治疗裸鼠皮下移植瘤的生长抑制率为70.1%,与顺铂组、米非司酮组(分别为22.5%、6.5%)比较,差异均有统计学意义(P＜0.05).结论 米非司酮通过下调ERCC1、BRCA1、hMLH1基因的表达及阻滞G0/G1期细胞、增加细胞凋亡率来增强顺铂对卵巢癌细胞的抗肿瘤敏感性.     

冻融抗原致敏的树突细胞对裸鼠人卵巢癌移植瘤治疗作用的研究

目的 :研究冻融抗原致敏的树突细胞 (DC)对裸鼠人卵巢癌移植瘤的治疗作用。方法 :联合应用粒性白细胞与巨噬细胞集落刺激因子 (GM CSF)及白介素 4 (IL 4 )从正常足月产妇分娩后新生儿脐血中培养出DC ,以人卵巢癌细胞系 3AO细胞冻融抗原激活DC ,测定其诱导的细胞毒性T淋巴细胞 (CTL)对 3AO的杀伤活性 ;CTL预防性接种于裸鼠皮下 ,观察裸鼠人卵巢癌移植瘤的发生率 ,以DC激活的CTL治疗裸鼠人卵巢癌移植瘤并观察治疗效果。结果 :体外抗原冲击致敏的DC能显著刺激T淋巴细胞增殖 ,其诱导的CTL对细胞系 3AO具有显著的杀伤作用 ,在效靶比为 4 0 :1、2 0 :1、10 :1、5 :1时 72h杀伤率平均分别为 90 .1%、67.4 %、4 0 .4 %、17.8%。DC激活的CTL能预防裸鼠人卵巢癌移植瘤的发生 (预防组 16.6% ,对照组 10 0 % ,P <0 .0 0 1) ,并能抑制移植瘤生长 ,对照组、治疗组移植瘤的大小分别为 (5 .6± 1.1)cm3 、(2 .7± 0 .78)cm3 (P <0 .0 1)。结论 :人卵巢癌细胞冻融抗原体外冲击致敏的DC可作为一种抗癌疫苗在免疫治疗卵巢癌患者中发挥重要作用     

人上皮性卵巢癌细胞系SKOV3-luc裸鼠皮下及原位移植瘤模型的建立与研究

目的:建立整体可视化人卵巢癌皮下和原位移植瘤模型,用于实时观察和分析人卵巢癌移植瘤发展和转移的规律,并比较两者的成瘤情况及生物学特性。方法:使用带有荧光素酶报告基因(Luciferase)的人上皮性卵巢癌细胞系SKOV3-luc分别接种于裸鼠右侧腋窝皮下和左侧卵巢内,建立人上皮性卵巢癌裸鼠皮下和原位移植瘤模型。实时观察卵巢癌细胞SKOV3-luc在裸鼠皮下和原位的生长情况,并切取肿瘤组织,应用病理组织学方法对裸鼠皮下移植瘤和原位移植瘤进行检测和评价。结果:人卵巢癌细胞系SKOV3-luc裸鼠皮下和原位移植瘤模型建立的成功率均较高。裸鼠皮下和左侧卵巢接种肿瘤细胞后,可通过活体成像实时观察肿瘤的生长情况,并且行定量分析肿瘤形成时间等。皮下移植瘤(皮下组)成瘤率为100%,左侧卵巢原位移植瘤(原位组)成功率为100%。注射后第7天,皮下组的肿瘤总荧光强度比值为(3.38±2.50)(Fold),原位组为(1.43±1.32)(Fold);第14天,皮下组为(15.73±11.70)(Fold),原位组为(6.44±7.26)(Fold),皮下组第7天和第14天的肿瘤总荧光强度比值均大于原位组(P<0.05)。结论:人上皮性卵巢癌裸鼠皮下移植瘤和卵巢原位移植瘤建模成功率高,并能很好地反应肿瘤的生物学行为,实时荧光成像便于观察肿瘤体内生长情况,为研究卵巢癌发展和转移提供了可靠的观察模型。     

TRAIL对3AO裸鼠移植瘤治疗作用的实验研究

目的 :探讨肿瘤坏死因子相关凋亡诱导配体 (TRAIL)对 3AO裸鼠皮下及腹腔移植瘤的治疗作用。方法 :将 5× 10 6 和 2× 10 7对数生长期的 3AO分别接种于BALB/C裸鼠右下肢皮下和腹腔内 ;待皮下组移植瘤长至 0 .2 5cm3,腹腔移植瘤组移植后 96h ,随机分为 5组。裸鼠皮下和腹腔移植瘤A、B组为TRAIL组 ,剂量分别为 0 .5 μg/ml和 1μg/ml;C组为TRAIL0 .5 μg/ml加cDDP 1.5mg/kg ,D组为cDDP 3mg/kg ;E组为对照组 (将生理盐水分别注射于瘤周和腹腔 ) ,观察移植瘤成瘤率、裸鼠生存期和生存期延长率。同时观察停药后 1d、1周、2周裸鼠移植瘤细胞的细胞凋亡率及CD95、Apo2 .7、P5 3、Bcl 2基因表达的变化。结果 :(1)A、B、C和D组裸鼠皮下移植瘤的抑制率分别为 2 3%、4 9.1%、6 2 .3%和 5 2 .6 % ,差异有显著性 (P <0 .0 5 ) ;(2 )腹腔移植瘤组 :A、B、C、D组裸鼠移植瘤的成瘤率分别为 89.1%、72 .3%、5 1.7%和 6 1.5 % ;差异有显著性 (P <0 .0 5 ) ;(3)TRAIL作用裸鼠移植瘤后CD95与Apo2 .7的表达均升高 ,P5 3基因表达稍升高 ,Bcl 2基因表达降低。结论 :(1)TRAIL对人卵巢癌裸鼠移植瘤有明显的抑制作用 ,TRAIL能明显降低裸鼠的成瘤率及死亡率 ,延长生存期 ;(2 )其机制可能与基因CD95、Apo2 .7、Bcl 2的调节有关     

mdr1启动子调控胞嘧啶脱氨酶-尿嘧啶磷酸核糖转移酶融合基因对卵巢癌裸鼠耐药移植瘤的抑制作用

目的:观察人多药耐药基因mdrl启动子调控的胞嘧啶脱氨酶-尿嘧啶磷酸核糖转移酶融合自杀基因(CD::upp)对紫杉醇耐药卵巢癌裸鼠皮下移植瘤的抑制作用及对荷瘤裸鼠生存时间的影响。方法:建立卵巢癌耐药及非耐药细胞的裸鼠模型,将含mdrl-CD::upp的重组腺病毒0．1ml(1×10~9 pfu/ml)注入裸鼠皮下移植瘤体内,腹腔内注射5-氟胞嘧啶(5-FC),观察各组裸鼠肿瘤生长速度及存活时间。结果:实验组裸鼠移植瘤明显受到抑制,与对照组的差异有统计学意义(P＜0．05)。实验组荷瘤裸鼠的生存时间明显延长,对照组在69天内全部死亡,差异有统计学意义(P＜0．001)。结论:mdrl启动子调控的CD::upp基因能特异性地抑制卵巢癌裸鼠耐药移植瘤的生长并延长生存时间。     

重组腺病毒bcl-xs基因对人卵巢癌裸鼠移植瘤作用的研究

目的 观察重组腺病毒bcl-xs基因（adv-bcl-xs基因,简称bcl-xs基因）对人卵巢癌裸鼠移植瘤的生长抑制和荷瘤裸鼠生存率的影响。为卵巢癌的基因治疗提供实验基础。方法 采用以复制缺陷型腺病毒bcl-xs基础感染的人胚肾细胞,使bcl-xs基因对NUTU-19细胞的生长抑制作用并检测其病毒滴度后,将bxl-xs基因导入人卵巢癌裸鼠移植瘤中,观察bcl-xs基因对腹水的生长抑制作用,计算裸鼠的生存时间,并观察bcl-xs基因对裸鼠全身和局部的毒副作用。电镜观察bcl-xs基因的病毒颗粒,以免疫细胞化学染色测定bcl-xs基因表达情况。结果 bcl-xs基因可在人胚肾细胞内扩增,对NUTU-19细胞有抑制和杀伤作用。并在裸鼠体内呈过度表达,使裸鼠腹水形成的时间由5-10d延长至11-23d,裸鼠平均生存时间由24d延长至39d,bcl-xs基因对裸鼠全身和局部无明显毒副作用。结论 bcl-xs基因导入人卵巢癌裸鼠移植肿瘤,能延缓腹水形成,延长裸鼠的生存时间,为卵巢癌的基因治疗提供了一种新方法。     

MG132对卵巢上皮性癌裸鼠移植瘤生长的影响及联合顺铂作用效应的研究

目的:探讨蛋白酶体抑制剂MG132应用于卵巢上皮性癌裸鼠移植瘤的新型治疗及联合顺铂协同抗肿瘤的潜在价值和可行性。方法:建立人卵巢癌裸鼠皮下移植瘤模型,20只裸鼠随机平均分为4组,每日腹腔内注射给药1次,共7日。对照组(0.2 ml的0.9%氯化钠液),MG132组(2 mg/kg),顺铂组(1 mg/kg),联合组[MG132(2 mg/kg)+顺铂(1 mg/kg)]。移植瘤模型建立4周后比较各组移植瘤质量抑制率,IHC、FIA、Western blot、RT-PCR检测各组肿瘤促凋亡基因(Caspase3)、自噬基因(Beclin1)的表达情况。结果:1顺铂组、MG132组、联合组对移植瘤的瘤质量抑制率分别为15.38%、53.85%、88.46%,顺铂联合MG132理论相加的瘤质量抑制率为60.95%;2IHC、FIA、Western blot检测:与对照组相比,顺铂组、MG132组、联合组Beclin1、Caspase3阳性表达均明显增强,其中联合组阳性表达更强。3RT-PCR检测:顺铂组、MG132组、联合组的Beclin1、Caspase3 mRNA表达均明显高于对照组(P0.05);且联合组又高于顺铂组、MG132组(P0.05)。结论:MG132对卵巢上皮性癌裸鼠移植瘤生长具有抑制作用,且与顺铂联合治疗卵巢癌具有协同抗肿瘤效应,有望成为治疗顺铂耐药型难治性卵巢癌的一种有效抗肿瘤药物。     

人卵巢癌裸鼠腹腔及网膜移植的研究

目的：建立既符合卵巢癌临床特征，又便于实验观察和分析的人卵巢癌裸鼠异种移植模型。方法：将体外培养的卵巢癌Ａｏ细胞接种于裸鼠皮下和腹腔内，并切取皮下移植瘤；在麻醉状态下对裸鼠进行网膜局部手术移植。结果：腹腔种植成瘤率为７０％（７／１０），肿瘤结节大小不一，分布广泛，其中２只腹水形成；网膜移植全部成瘤，移植瘤呈单一生长，易分离和切除，肿瘤重量一致性较好。结论：人卵巢癌裸鼠网膜异种移植模型直接反映肿瘤生物学行为，便于观察和分析实验结果，适于在卵巢癌实验研究中应用。     

Characteristics of calcifying odontogenic cyst in Taiwanese.

BACKGROUND AND PURPOSE: Calcifying odontogenic cyst (COC) is a rare type of odontogenic cyst. This retrospective study analyzed the clinical, radiographic, and histopathologic features of COC in Taiwanese. METHODS: Ten cases of COC in 2 male and 8 female patients with a mean age of 29 years (range, 11 to 48 years) treated from January 1985 to December 2002 were included. Microscopic slides, clinical histories, and radiographic features of these 10 COC cases were reviewed and analyzed. RESULTS: COCs occurred in the maxilla in 3 cases and in the mandible in 7 cases. COCs were associated with impacted teeth in 6 cases and with odontomas in 3 cases. All COCs appeared as either unilocular (9 cases) or multilocular (1 case) radiolucencies. In 7 cases, spotty radiopaque materials were scattered throughout the radiolucency. Histologically, all of the lesions were at least partially lined by epithelium with cuboidal to columnar basal cells and stellate reticulum-like suprabasal cells. Variable numbers of ghost cells, some of which were calcified, were observed in the lining epithelium or in the fibrous connective tissue wall of all 10 cases. Juxta-epithelial dentinoid was also found in all cases. However, proliferation of ameloblastoma-like tumor nests was observed in only 1 case. Based on the above histologic findings, 6 COC lesions were classified as simple unicystic type, 3 as unicystic odontoma-producing type, and 1 as unicystic ameloblastomatous proliferating type. CONCLUSIONS: COC occurs frequently in the second and third decades and is commonly associated with an impacted tooth or an odontoma. It usually appears as a mixed radiolucent and radiopaque lesion radiographically. Simple unicystic type is the most common type of COC. No recurrences were found after conservative surgical removal in this series.     

Oral contraceptives use and weight gain in women with a Central European life-style.

OBJECTIVES: The aim of the study was to check and present data on the relation between combined oral contraceptives (COC) use and body weight in young women living in Poland. METHODS: Observational study on the group of young women on COC and the control group of young women who never used COC. Candidates for study (145 women) and control (218 women) groups were recruited in selected gynecological clinics in Poland during the period of 1-31 January 2002 (with the use of randomization). RESULTS: Both groups (study and control) were almost identical in age, anthropometric characteristics, number of pregnancies and deliveries. On the basis of this investigation it was found that there was no relation between use of COC and weight gain. Observed (in both groups) weight gain in young women was most probably related rather to time-passing (patients were getting older). The higher risk for overweight and obesity was found in the group of young women who had already had problems with overweight in their childhood. and in the group of women with high weight gain during the first pregnancy. CONCLUSION: COC use is not associated with weight gain in young women with a Central European life-style.     

The effect of clomiphene citrate on osteoporosis in ovariectomized rats

OBJECTIVE: The aim of this study was to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contraindication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. STUDY DESIGN: This study was carried out in the Experimental Surgery Laboratory of the Brain Research Centre of the Medical Faculty of Ege University. Four-month-old Sprague-Dawley rats were used for the experiment. The study was carried out on six groups of animals each consisted of eight rats. Four groups of rats were ovariectomized and 2 groups of rats were used as control group. For 6 weeks every day, rats were injected physiological saline solution (1 ml/kg), clomiphene citrate (1 or 10 mg/1 ml/kg, Organon), 17beta-estradiol (50 microg/1 ml/kg, within susame oil, Sigma) or susame oil (1 ml/kg, Sigma). Drug administrations were carried out according to the weekly weight measurements. Group 1(PSS), n = 8, non-ovariectomized, were injected with physiological saline solution. Group 2(CC-1), n = 7, non-ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 3(OVX + CC-1), n = 7, ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 4(OVX + CC-10), n = 6, ovariectomized, were injected with CC (10 mg/1 ml/kg). Group 5(OVX + E), n = 8, ovariectomized, were injected with 17beta-estradiol (50 microg/1 ml/kg). Group 6(OVX), n = 8, ovariectomized, were injected with susame oil (1 ml/kg) Bone-specific serum alkaline phosphatase (ALP) levels were measured and statistical analyses were made by Kruskal Wallis test. Left femur bone histomorphometric studies were done. The uteri were dissected out to measure their weight and ANOVA was used to show the intergroup differences. RESULTS: The level of ALP in group 3 was significantly higher than the other five groups. Bone histomorphometric examination showed that total bone volume in group 3, 4, and 5 was higher than group 6, and group 4 had the highest level of bone volume compared to the rest of the groups. Uterus weights in group 1 were significantly higher than group 3 and 6 (P = 0.02, P = 0.01) and uterus weights in group 5 were significantly higher than group 3 and 4 (P = 0.00, P = 0.01) CONCLUSIONS: In ovariectomized rats, treatment with CC is seen as effective as estrogen treatment in preventing osteoporosis, without causing uterin hyperstimulation. Nevertheless, further investigations on more rats are needed to assess whether it is an alternative treatment method to estrogen.     

达那唑海藻酸钠微球用于兔子宫动脉栓塞术后对其卵巢功能和妊娠的影响

目的 观察达那唑海藻酸钠微球（DKMG）用于兔子宫动脉栓塞术后对其卵巢功能和妊娠的影响。方法 选择32只雌性大耳白家兔，随机分为3组，即DKMG栓塞组（DKMG组，12只）、海藻酸钠微球（KMG）栓塞组（KMG组，12只）和未进行子宫动脉栓塞组（对照组，8只）。比较3组兔栓塞术前和术后1～3个月血清雌二醇、卵泡刺激素（FSH）、黄体生成素（LH）、睾酮水平，观察DKMG用于子宫动脉栓塞术后对卵巢功能的影响，同时配种繁育观察DKMG对兔妊娠的影响。结果 子宫动脉栓塞术后1—3个月，3组兔血清雌二醇、FSH、LH、睾酮水平分别与自身栓塞术前比较，差异均无统计学意义（P〉0．05）。术后2～4个月的累积妊娠率，DKMG、KMG组均为0，与对照组（4／8）比较，差异有统计学意义（P〈0．05）；术后5～7个月的累积妊娠率，DKMG、KMG、对照组分别为17％（2／12）、25％（3／12）、5／8，3组间比较，差异无统计学意义（P〉0．05）；术后8—10个月的累积妊娠率，DKMG、KMG、对照组分别为42％（5／12）、50％（6／12）、6／8，3组间比较，差异也无统计学意义（P〉0．05）。结论 DKMG用于子宫动脉栓塞术后对兔卵巢功能没有明显影响；栓塞术后兔有成功妊娠，但近期妊娠率受到影响。     

单己糖神经酰胺与卵巢癌顺铂耐药性关系的研究

目的　研究单己糖神经酰胺 (ceramidemonohexoside ,CMH)与卵巢癌顺铂耐药细胞株COC1 DDP细胞的顺铂耐药性的关系 ,及其在COC1 DDP细胞凋亡中的作用。方法　分别提取、纯化COC1 DDP细胞 (用浓度为 1 2 5、5μmol L的米非司酮处理前、后 )和卵巢癌顺铂敏感细胞株COC1细胞的中性鞘糖脂 ,用高效薄层层析、凝胶光密度成像系统分析细胞中CMH的相对含量。将COC1 DDP细胞分为 :顺铂 ( 0 1、0 2 5、0 5、1 2 5、2 5μg ml)组、米非司酮 ( 1 2 5、2 5、5、10、2 0 μmol L)组、顺铂 ( 0 1～2 5μg ml) +米非司酮 ( 1 2 5、5μmol L)组 ,用四甲基偶氮唑蓝 (MTT)法检测各组细胞的生存率、琼脂糖凝胶电泳检测各组细胞DNA的变化、透射电子显微镜观察各组细胞的形态变化。结果　COC1 DDP细胞中CMH的相对含量为 ( 3 7 1± 3 3 ) % ,明显高于COC1细胞的 ( 14 1± 1 4) % (P <0 0 0 1) ;COC1 DDP细胞分别经 1 2 5、5μmol L米非司酮处理后 ,CMH的相对含量下降到 ( 2 6 6± 2 6) %和 ( 17 5±0 7) % ,分别与米非司酮处理前比较 ,差异均有显著性 (P <0 0 5,0 0 0 1)。MTT法检测显示 ,米非司酮浓度在 5μmol L以下时 ,对COC1 DDP细胞不产生明显的抑制作用 (P >0 0 5) ;顺铂 +米非司酮组COC1 DDP细胞抑制率较     

Caspase-3活性改变与人卵巢癌细胞系COC1/DDP耐药的关系

目的 探讨人卵巢癌顺铂耐药细胞株COC1/DDP中抗凋亡蛋白Bcl-XL、Bcl-2、细胞色素C的表达及半胱天冬氨酸蛋白酶-3(caspase-3)活性与人卵巢癌顺铂耐药的关系。方法:采用RT-PCR和Western Blot分析人卵巢癌顺铂敏感细胞株COC1和顺铂耐药株COC1/DDP中Bcl-XL、Bcl-2、细胞色素C的表达和caspase-3的活性。并用流式细胞术测定顺铂作用后COC1和COC1/DDP细胞株的凋亡率。结果:在COC1/DDP细胞中,Bcl-XL和Bcl-2的表达明显高于COC1细胞;顺铂作用后,在COC1/DDP细胞株中细胞色素C的表达明显减少,caspase-3活性明显降低(P<0.05);其凋亡率也明显低于COC1细胞株(P<0.05)。结论:人卵巢癌细胞株COC1/DDP对顺铂产生耐药可能与细胞内Bcl-XL、Bcl-2过度表达抑制了线粒体细胞色素C的释放及caspase-3活性有关。     

Effect on quality of life of switching to combined oral contraception based on natural estrogen: an observational,multicentre, prospective phase IV study (ZOCAL Study)

Objectives: This observational, multicentre, prospective phase IV study examined change in health-related quality of life (QOL) from baseline to 6 months in women initiating combined oral contraception (COC) based on natural estrogen.

Methods: Eligible women attending a baseline and 6-month gynaecology appointment belonged to one of three groups: group 1 used barrier contraception (condoms) and elected to continue this method; group 2 used condoms and elected to switch to COC based on natural estrogen; group 3 used COC based on ethinylestradiol and elected to switch to COC based on natural estrogen. The Spanish Society of Contraception (SEC)-QOL scale assessed health-related QOL. Secondary outcomes included symptoms of premenstrual syndrome, intermenstrual bleeding, duration and intensity of menstrual bleeding, contraception continuation rate, and tolerability.

Results: A total of 857 women were enrolled and 785 completed the study. Group 2 (n?=?224 completed) had significantly lower SEC-QOL global and dimension scores at baseline and significantly greater increases in SEC-QOL from baseline to 6 months compared with groups 1 (n?=?72) and 3 (n?=?489). Group 3 reported a similar SEC-QOL score to that of group 1 at baseline but showed significantly greater improvement in SEC-QOL global and psychological scores from baseline to 6 months. Among women receiving COC based on natural estrogen, the contraception continuation rate was 713/780 (91.4%); treatment-related adverse events were reported by 13/780 (1.7%).

Conclusions: Improved SEC-QOL after 6 months was found in women who were dissatisfied with their current contraception at baseline and chose to switch to COC based on natural estrogen.     

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15?μg ethinylestradiol [EE] and 120?μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30?μg EE and 3?mg drospirenone in healthy Chinese women aged 18–40 years.

Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.

Results: Participants were randomised either to the NuvaRing (n?=?732) or to the COC (n?=?214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.

Conclusions: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.     

RelA反义寡核苷酸对卵巢癌细胞株COC1凋亡的影响

目的　探讨RelA反义寡核苷酸对卵巢癌细胞株COC1凋亡的影响。方法　应用不同浓度的肿瘤坏死因子 (TNF)α或泰素结合RelA反义寡核苷酸 ,分别处理COC1细胞株 ;应用间接免疫荧光、Westernblot、流式细胞术、DNA凝胶电泳等方法 ,检测RelA活化及COC1细胞凋亡。结果　 5 0nmol/L的泰素单独及其与RelA反义寡核苷酸联合处理COC1细胞 12h后 ,COC1细胞的凋亡率分别为 (12 3± 0 6 ) %、(2 7 4± 0 5 ) % ,两者比较 ,差异有极显著性 (P <0 0 1) ;2 4h后 ,COC1细胞凋亡率分别为 (13 0± 0 5 ) %、(31 7± 0 3) % ,两者比较 ,差异有极显著性 (P <0 0 1)。 5 0 μg/L的TNFα单独及其与RelA反义寡核苷酸联合处理COC1细胞 12h后 ,COC1细胞凋亡率分别为 (13 2± 0 4 3) %、(30 8± 0 3) % ,两者比较 ,差异有极显著性 (P <0 0 1) ;同样 10 0 μg/L及 2 5 0 μg/LTNFα单独及其与RelA反义寡核苷酸联合处理COC1细胞的凋亡率相比 ,差异均有极显著性 (P <0 0 1)。结论　RelA反义寡核苷酸可增加TNFα或泰素诱导卵巢癌细胞凋亡的敏感性。     

Apoptosis induced by cisplatin and verapamil or SDZ PSC 833 in human ovarian cell lines]

OBJECTIVE: To study the pharmaceutical mechanisms of cisplatin (DDP), verapamil (VP) and SDZ PSC833, and the mechanism of developing acquired drug resistance. METHODS: Two ovarian carcinoma cell lines--one sensitive (COC(1)) and the other resistant (COC(1)/DDP) to cisplatin were used in this study. The cell viability was measured by trypan blue dye exclusion assay. The apoptotic cells were observed and distinguished by light and electron microscopy, and comet assay. Flow cytometry was used to measure the cell cycle. Six groups were set up according to drug(s) delivered: DDP, VP, SDZ PSC833, DDP and VP, DDP and SDZ PSC833, and control group. RESULTS: (1) VP or SDZ PSC833 enhanced cytotoxicity of DDP (q > 1, P < 0.01). (2) The most prominent effect of DDP on cell cycle kinetics was a slowdown in S-phase transit during which cells undergo apoptosis (P < 0.05). (3) COC(1) and COC(1)/DDP cells had different rates of apoptosis when DDP added. SDZ PSC833 enhanced apoptosis of COC(1)/DDP cells induced by DDP. CONCLUSIONS: VP and SDZ PSC833 increase sensitivity of the cell lines to DDP. SDZ PSC833 enhances apoptosis induced by DDP. Induction of apoptosis is one of the pharmaceutical mechanisms of DDP, and acquired drug resistance is associated with resistance to apoptosis. The most prominent effect of DDP on cell cycle kinetics is a slowdown in S-phase transit and apoptotic cells are at S-phase.