Aspirin use and endometrial cancer risk and survival

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E₂ suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use.     

子宫内膜癌肿瘤微环境内IGFBP-3表达及其对肿瘤侵袭能力的影响

目的:探讨子宫内膜癌肿瘤微环境内IGFBP-3表达与肿瘤-间质相互作用的关系,以及IGFBP-3表达对子宫内膜癌侵袭能力的影响。方法:免疫组化法检测子宫内膜癌、正常子宫内膜组织中IGFBP-3的表达情况。肿瘤相关成纤维细胞(CAF)、正常内膜成纤维细胞(NF)与子宫内膜癌Ishikawa细胞在Transwell小室内共培养,RT-PCR、ELISA法检测IGFBP-3表达水平的改变。Transwell侵袭实验评估IGFBP-3表达改变对Ishikawa细胞侵袭能力的影响。结果:子宫内膜癌组织中IGFBP-3表达显著低于正常子宫内膜组织(P0.01)。CAF、NF与Ishikawa细胞共培养后,两种间质成纤维细胞中IGFBP-3 mRNA表达水平均显著下降(P0.01);而在Ishikawa细胞,CAF可使其IGFBP-3 mRNA表达显著降低(P0.01),但NF对其无显著影响(P0.05)。CAF、NF均能促进Ishikawa细胞的侵袭能力;与单Ishikawa细胞组和NF+Ishikawa共培养组相比,CAF共培养能显著增加Ishikawa细胞的侵袭能力(113.33±8.50 vs 65.17±10.23、75.33±8.21,P0.01)。而加入外源性重组人IGFBP-3后,能显著抑制CAF的促侵袭作用。结论:子宫内膜癌肿瘤与间质相互作用可导致肿瘤微环境内IGFBP-3表达下降,而肿瘤微环境IGFBP-3表达的改变与子宫内膜癌的生长、侵袭和转移密切相关。     

Platelet-derived growth factor promotes endometrial epithelial cell proliferation

OBJECTIVE: Our purpose was to determine the effects of platelet-derived growth factor on the proliferation of endometrial epithelial cells. Platelet-derived growth factor and its receptors have been identified in the endometrium, and platelet-derived growth factor is a mitogen for endometrial stromal cells. Released from macrophages and platelets at sites of ectopic endometrial growth, platelet-derived growth factor could promote the progression of endometriosis and endometrial cancer.STUDY DESIGN: Endometrial epithelail cell lines were developed from proliferative-phase endometria from two patients without endometrial lesions. Cell lines were confirmed to be epithelial. Proliferation assays were conducted on both lines with recombinant human platelet-derived growth factor-AA, AB, and BB. Assays were also performed at different doses, times, and cell densities with platelet-derived growth factor-AB.RESULTS: All isoforms of platelet-derived growth factor were potent mitogens for both endometrial epithelial cell lines. The greatest proliferative responses were achieved at 10 ng/ml and at 24 hours. Responses decreased significantly in confluent cultures.CONCLUSIONS: These results suggest that endometrial epithelial cells have functional platelet-derived growth factor-α receptors that signal cell replication. The greater activity of platelet-derived growth factor in subconfluent cultures may indicate that receptor numbers or affinity are up-regulated when cell-cell contact is disrupted. These data support a role for platelet-derived growth factor in normal endometrial proliferation and in pathologic proliferation such as endometriosis and endometrial cancer.     

半枝莲体外抗子宫内膜癌活性的研究

目的:研究半枝莲不同极性部位体外抗子宫内膜癌细胞Ishikawa的活性作用。方法:采用MTT法检测半枝莲不同极性部位对子宫内膜癌细胞Ishikawa的增殖抑制作用;采用平板克隆形成实验检测活性最强部位对Ishikawa细胞克隆形成能力的影响;应用流式细胞仪检测活性最强部位对Ishikawa细胞周期分布的影响。结果:半枝莲不同极性部位对子宫内膜癌细胞Ishikawa均有不同程度的抑制作用,其中氯仿部位的抑制作用最强(IC50=146.494μg/ml)。随着供试药物浓度的升高,细胞克隆形成能力降低;半枝莲氯仿部位对Ishikawa细胞表现为S期、G2/M期阻滞作用。结论:半枝莲氯仿部位是半枝莲抗子宫内膜癌细胞Ishikawa的最主要有效部位。     

Perimenopausal use of reproductive hormones effects on breast and endometrial cancer

The effect of reproductive hormone use in the form of oral contraception or HRT on endometrial cancer incidence is not caused by simply bias: the epidemiologic studies are consistent; the effect of ERT is large; the biologic rationale cited is a plausible mechanism; and the response to progestin in oral contraception or combined HRT tends to confirm the biologic mechanism. In contrast, it remains unclear whether changes in breast cancer incidence following use of oral contraception and HRT are caused by hormone exposure or to other factors: the results of epidemiologic studies are not entirely consistent, and the smaller relative effect on risk of breast cancer is susceptible to bias and other sources of error. Although the exact nature of the association between repro ductive hormone use and breast cancer incidence is not yet clear, breast cancer is a common neoplasm in older women. Prescribers and users should take this into account in weighing benefits to ensure that unnecessary risks are avoided.     

氧化苦参碱抑制子宫内膜癌细胞株Ishikawa的实验研究

目的:观察不同浓度氧化苦参碱(oxymatrine,Oxy)对人子宫内膜癌细胞株Ishikawa增殖抑制及诱导凋亡作用。方法:培养人子宫内膜癌细胞株Ishikawa,通过细胞形态学观察、CCK-8比色法检测细胞增殖,流式细胞仪检测细胞凋亡及细胞周期人工重组基底膜侵袭小室(transwell)观察细胞的侵袭力。结果:Oxy明显抑制Ishikawa增殖,并呈时效和量效关系,24h、48h、72h的IC50分别为8.07,4.62,3.22mg/ml;细胞周期发生明显改变。随着药物浓度增高,G1期细胞比例增加,S期细胞减少;流式细胞仪可检测到细胞凋亡现象,当Oxy浓度为10mg/ml时,细胞凋亡率65.4%;荧光显微镜可见细胞凋亡形态学变化;Ishikawa细胞侵袭基底膜的能力明显被抑制。结论:Oxy可抑制Ishikawa增殖,诱导Ishikawa细胞凋亡,有可能成为治疗子宫内膜癌的有效药物。     

5-氮杂脱氧胞苷对子宫内膜癌细胞的生长及RASSF1A基因表达的影响

目的 探讨DNA甲基转移酶抑制剂--5-氮杂脱氧胞苷(5-Aza-CdR)对子宫内膜癌细胞的生长及RASSF1A基因表达的影响.方法 5-Aza-CdR作用后,采用锥虫蓝染色法、流式细胞仪分别检测子宫内膜癌细胞株HEC-1B细胞的生长及凋亡情况,采用RT-PCR技术、甲基化特异性PCR(MSP)技术分别检测HEC-1B细胞中RASSF1A mRNA的表达和RASSF1A基因启动子的甲基化状态.结果 (1)HEC-1B细胞的生长及凋亡情况:5-Aza-CdR对HEC-1B细胞生长的抑制作用呈明显的剂量和时间依赖性(P＜0.01);且HEC-1B细胞的凋亡率也呈明显的剂量依赖性(P＜0.01).(2)HEC-1B细胞中BASSF1A mRNA的表达:未经5-Aza-CdR作用的HEC-1B细胞中BASSF1A mRNA表达缺失;不同浓度5-Aza-CdR(分别为0.05、0.1、1、5、10 nmol/ml)作用后,HEC-1B细胞中RASSF1AmRNA表达不同程度地上升,其相对表达水平分别为0.074±0.004、0.105±0.004、0.167±0.006、0.334±0.005、0.484±0.007,分别与未经5-Aza-CdR作用的细胞(为0)比较,差异均有统计学意义(P＜0.01).(3)HEC-1B细胞中RASSF1A基因启动子的甲基化状态:未经5-Aza-CdR作用的HEC-1B细胞中RASSF1A基因启动子呈高甲基化状态;加入低浓度(即0.05、0.1、1、5 nmol/ml)的5-Aza-CdR后,HEC-1B细胞中RASSF1A基因启动子的甲基化水平下降,呈半甲基化状态(即同时出现甲基化和非甲基化条带);当5-Aza-CdR浓度为10 nmol/ml时,HEC-1B细胞中RASSF1A基因启动子呈非甲基化状态.结论 (1)5-Aza-CdR可抑制HEC-1B细胞增殖、促进HEC-1B细胞凋亡.(2)5-Aza-CdR能使HEC-1B细胞重新表达RASSF1A mRNA,能逆转RASSF1A基因启动子的高甲基化状态.     

Clinical studies on endometrial cancer

One hundred and fifty-two cases with endometrial carcinoma were treated in our clinic between 1973 and 1985. The average age was 55.89 years, and the age range was from 29 to 76 years. Thirty-six cases (23.7%) were nulligravidas and 42 cases (27.6%) were nulliparas. One hundred and ten cases (72.4%) were postmenopausal and the average age at menopause was 49.1 years. The most frequent chief complaint was atypical genital bleeding which was noted in 128 cases (84.2%). The result of a cytologic examination of the uterine cervix was positive in 50.7% and suspicious in 16.9% but results for the endometrium were positive in 63% and suspicious in 21.9%. The cases in this study were classified into 88 cases (57.9%) of T1a, 36 cases (23.7%) of T1b, 12 cases (7.9%) of T2, 3 cases (2.0%) of T3 and 1 case (0.7%) of T4. As to the postoperative diagnosis, there were classified into 86 cases (56.6%) of pT1a, 30 cases (19.7%) of pT1b, 19 cases (12.5%) of pT2, 10 cases (6.6%) of pT3 and 5 cases (3.3%) of pT4. Histopathologically almost all 140 cases (91.41%) were of adenocarcinoma and classified into 88 cases (57.9%) of G1, 39 cases (25.7%) of G2 and 13 cases (8.6%) of G3. The cumulative survival rates after Kaplan-Meier were 95% in pT1a cases, 75.6% in pT1b cases, 67.3% in pT2 cases, 42.2% in pT3 cases and 0% in pT4 cases.     

RANKL对人子宫内膜癌细胞上皮间质转化的影响

目的:探讨RANKL对人子宫内膜癌细胞转移和上皮间质转化的影响。方法:体外构建针对细胞核因子κB受体活化因子(RANK)的过表达质粒载体(p IRES2-3FLAG-EGFP-RANK),脂质体法转染人子宫内膜癌HEC-1A细胞株,形成HEC-1ARANK细胞(过表达质粒组),并与HEC-1A~Control细胞(空白质粒组)相对照。给予1μg/ml可溶性细胞因子sRANKL处理后,细胞划痕试验检测细胞迁移能力,CCK-8试验检测细胞的增殖能力,实时荧光定量PCR(qRT-PCR)和Western blot技术分别检测EMT相关指标E-cadherin、N-cadherin及Vimentin mRNA及蛋白的表达变化。结果:经1μg/ml sRANKL刺激后,HEC-1ARANK细胞迁移能力增强(P0.01),增殖效应没有明显改变(P0.05),上皮性标记物E-cadherin mRNA及蛋白的表达水平下降,间质性标记物N-cadherin、Vimentin mRNA及蛋白的表达水平显著上调(P0.01)。结论:RANKL可通过诱导HEC-1A细胞发生上皮间质转化促进子宫内膜癌的转移。     

阿司匹林对宫颈癌细胞系Caski的生长抑制作用

目的　探讨阿司匹林对宫颈癌细胞系Caski作用。方法　利用细胞计数法对宫颈癌细胞系Caski细胞进行活细胞计数 ,利用流式细胞仪检测细胞DNA含量。结果　阿司匹林对宫颈癌细胞系Caski细胞的抑制呈剂量依赖性 ,在 1- 5mM浓度范围内 ,生长抑制率为 2 0 %～ 86 %。阿司匹林作用后的Caski细胞呈现出G1和G2期细胞数目增加 ,而S期细胞数目减少的趋势。结论　阿司匹林对宫颈癌细胞系Caski有抑制作用