人肿瘤坏死因子-α基因转导绒癌耐药细胞系体外耐药逆转的研究

目的 将人肿瘤坏死因子-alpha(hTNF-α)基因导入已建立的绒癌耐药细胞系，观察hTNF-α基因转导后对绒癌细胞耐药性逆转的体外作用。方法 通过阳离子脂质体将hTNF-α基因转导绒癌耐药细胞系，用新霉素筛选含hTNF-α片段的单细胞克隆，用RT-PCR方法和细胞免疫组织化学方法，检测转导hTNF-α基因的耐药细胞中MDRl mRNA和MDRl蛋白(P-gp)表,达水平的改变。采用四甲基偶氮唑蓝比色法，检测转导hTNF-α基因的耐药细胞对足叶乙甙(VP-16)的耐药指数。结果 转导hTNF-α基因后，绒癌耐药细胞中检测出hTNF-α mRNA表达，转导hTNF-α基因在mRNA水平能一定程度的逆转绒癌耐药细胞的MDRl，而在P-gp蛋白水平几乎能完全逆转绒癌耐药细胞的MDRl。转导hTNF-α基因的细胞的耐药指数明显降低。结论 hTNF-α基因转导后，可通过调节MDRl的表达，来逆转绒癌耐药细胞系的耐药性。     

滋养细胞肿瘤153例临床分析

目的 分析滋养细胞肿瘤的临床特点和综合治疗后的预后转归，探讨滋养细胞肿瘤临床各期的最佳治疗方法。方法 收集1988年1月至2000年12月收治的恶性滋养细胞肿瘤共153例，分析经化疗或手术治疗后的临床转归。结果 绒癌治愈率76．19％，侵蚀性葡萄胎治愈率为90，99％。结论 滋养细胞肿瘤的化疗效果可靠，对于Ⅱ期以上病例，采用以全身化疗为主，辅以多种途径的给药方式，疗效更佳。     

介入治疗绒毛膜癌的疗效分析

目的探讨经动脉灌注化疗(TAC)在绒毛膜癌的治疗中的优点及其临床应用价值.方法统计23例行TAC治疗绒癌病例,采用Seldinger法,动脉插管后选择性置管于肿瘤供血动脉内,灌注5-氟尿嘧啶(5-Fu)、平阳霉素(PYM),治疗间隔20～25天,随访观察临床表现、肿瘤情况和病人的生存时间.结果绒癌多发于生育期妇女,Ⅰ期绒癌治愈率达80%以上,有效率超过95%.结论介入治疗是绒癌的有效治疗手段,介入治疗效果显著,且保留子宫,提高生存及生命质量,治愈率高,较静脉化疗更为优越.     

化疗联合甲羟孕酮治疗侵蚀性葡萄胎与绒毛膜癌的疗效观察

目的观察化学治疗（化疗）加用甲羟孕酮（MPA）治疗侵蚀性葡萄胎及绒毛膜癌（绒癌）患者的临床疗效。方法侵蚀性葡萄胎及绒癌患者25例，进行自身对照。按常规方法应用氟尿嘧啶、更生霉素8 d疗程，第1疗程不用MPA为对照组，第2疗程开始前1周加用MPA 200 mg·d 1口服为试验组；远期10例Ⅲ期为远期组（未用MPA），近期10例Ⅲ期为近期组（加用MPA）。观察化疗前后两组食欲、恶心、呕吐、口腔溃疡等情况；两组化疗前后白细胞变化及细胞因子白细胞介素 6（IL 6）的变化；比较近期组和远期组化疗疗程数及肺转移结局。结果试验组食欲、恶心、呕吐、口腔溃疡等明显好于对照组（P＜0.01)；试验组化疗前后白细胞无明显变化（P＞0.05），对照组化疗后白细胞明显下降(P＜0.01)；试验组细胞因子IL 6明显低于对照组（P＜0.01)；近期组化疗疗程数明显低于远期组，肺转移灶消失时间短于远期组（P＜0.01）。结论MPA降低了细胞因子IL 6血清水平，改善了肿瘤化疗患者的生活质量；保护骨髓免于化疗毒性作用，增加了患者对化疗的耐受性；MPA良好的临床作用与其抑制肿瘤新生血管作用有关。     

An autopsy case of primary mixed choriocarcinoma and mature teratoma located in the thymic region associated with elevated human chorionic gonadotropin levels and characteristic testicular changes

An autopsy case of a 19-year-old male Japanese student with a primary mixed choriocarcinoma and mature teratoma in the thymic region is reported. The patient died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior mediastinal mass was found to be in contact with the thymic gland. The mass weighed 270 g and measured 12.5 cm × 10 cm × 5 cm. The left thoracic cavity contained 2200 ml bloody pleural effusion and 200 g coagula due to hemorrhage from the tumor. Metastasized choriocarcinoma was seen in both lungs and the liver. High serum levels of human chorionic gonadotropin (HCG, 1 634 000 mIU/ml) and a decreased weight of the testes (2.0 g each) with Leydig cell hyperplasia/hypertrophy and the seminiferous tubules with hyaline ghost tubules or Sertoli cell only tubules were seen; other male reproductive organs were histologically normal. Although the serum testosterone level was within the normal range (5.75 ng/ml), luteinizing hormone (LH, 0.1 mIU/ml) and follicle-stimulating hormone (FSH, 0.3 mIU/ml) levels were decreased. High serum levels of HCG and characteristic testicular changes are drscribed.     

Choriocarcinome gestationnel révélé par une métastase rénale

Gestational choriocarcinoma (GC) belongs to a group of gestational trophoblastic tumors. This rare tumor has a great metastatic potential and thus requires an early and adapted treatment. Herein We report a case of GC in a 35-year-old patient who presents with hematuria from a renal metastasis. Clinical improvement was noted after nephrectomy and chemotherapy. This observation underlines the importance of the dosage of the beta-HCG and the polymorphic clinical presentation of gestational choriocarcinoma.     

AKR1C3 Overexpression Mediates Methotrexate Resistance in Choriocarcinoma Cells

Background: Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX.Methods: RNA interference technology, colony formation, and MTT assays were used to investigate the role of aldo-keto reductase family 1, member C3 (AKR1C3) in MTX resistance in choriocarcinoma cells.Results: AKR1C3 expression was higher in JeG-3R cells compared to JeG-3 cells and targeted inhibition of AKR1C3 expression with shRNA suppresses growth of choriocarcinoma cells as measured by colony formation and MTT assays. Overexpression of AKR1C3 increased chemotherapeutic resistance in JeG-3 cells. Furthermore, AKR1C3 silencing increases sensitivity to MTX in JeG-3R choriocarcinoma cells. Increasing MTX sensitivity spears to be related to DNA damage induction by increased reactive oxygen species (ROS), apoptosis, and cell cycle arrest.Conclusions: Data show that AKR1C3 is critical to the development of methotrexate resistance in choriocarcinoma and suggest that AKR1C3 may potentially serve as a therapeutic marker for this disease.     

Non-myxoma neoplastic cerebral aneurysms: A systematic review

Neoplastic cerebral aneurysms (NCAs) are highly rare lesions characterized by invasion of cancerous cells within the wall of an artery leading to aneurysm formation. While NCAs caused by myxomas are well characterized in the clinical literature, rarer etiologies have also been reported and are typically associated worse clinical outcomes. We performed the first PRISMA-compliant systematic literature review of true, non-myxoma neoplastic cerebral aneurysms using the PubMed/MEDLINE, Embase, Scopus, and Google Scholar databases. Data of interest included age, sex, aneurysm size, number of aneurysms, aneurysm location, neoplasm type, aneurysm treatments, cancer treatments, risk of rupture, intracerebral hemorrhage prevalence, subarachnoid hemorrhage prevalence, and survival at 90 and 180 days. A total of 50 studies met our inclusion criteria. The mean age of the patient population was 37.4 years (SD: ±16.8) and had an overall female preponderance (39/50, 78%). Of these NCA cases, 29/50 (58.0%) were choriocarcinomas, 10/50 (20.0%) were related to lung cancer, and 11/50 (22.0%) had other origins of variable pathologies. 90-day survival rates were 60.0% (15/25) for choriocarcinomas, 28.6% (2/7) for the lung cancer group, and 14.3% (1/7) for the other origins group. 180-day survival rates were 52.0% (13/25) for the choriocarcinoma group, 14.3% (1/7) for the lung cancer group, and 0% (0/7) for the other origins group. Prognosis of NCA patients ultimately depends on the course of disease progression and cancer management. Further research is needed to better understand optimal treatment modalities for patients with NCAs.     

乙酰肝素酶与绒毛膜癌侵袭能力的关系

目的 通过研究乙酰肝素酶（Hpa）在绒毛膜癌高、低侵袭力细胞系及正常早孕绒毛组织中的表达情况,探讨Hpa与绒毛膜癌侵袭能力的关系。方法 通过Matrigel体外侵袭实验检测不同侵袭力绒毛膜癌细胞系JEG-3和JAR的体外侵袭能力;应用免疫细胞化学方法及蛋白印迹法（westem blot）检测Hpa蛋白在不同绒毛膜癌细胞系及正常早孕绒毛组织中的表达,并进行相关性分析。结果 （1）JEG-3细胞的穿膜细胞数[（191±17）个]较JAR细胞的穿膜细胞数[（106±13）个]明显增多,两者比较,差异有统计学意义（P〈0．05）。（2）Hpa蛋白在绒毛膜癌细胞JEG-3、JAR中均有表达,且主要定位于细胞质。（3）在正常早孕绒毛组织、JEG-3细胞和JAR细胞中均可检测到Hpa蛋白,JEG-3细胞中Hpa蛋白的表达量（1．560±0．180）明显高于JAR细胞Hpa蛋白的表达量（0．610±0．170）,绒毛膜癌细胞系中Hpa蛋白的表达量又显著高于正常早孕绒毛组织Hpa蛋白的表达量（0．190±0．008）,两两比较,差异均有统计学意义（P〈0．05）。（4）相关性分析显示,Hpa蛋白的表达量与绒毛膜癌细胞体外侵袭能力呈正相关关系（r=0．89,P〈0．05）。结论 Hpa蛋白在绒毛膜癌细胞中表达较正常绒毛组织高;Hpa蛋白在滋养细胞中的表达随滋养细胞侵袭能力的增加其表达上调;滋养细胞产生过量的Hpa对基底膜蛋白的水解作用在绒毛膜癌的侵袭、转移中发挥重要作用。     

IMP1 promotes choriocarcinoma cell migration and invasion through the novel effectors RSK2 and PPME1

Objective

Oncofetal protein insulin-like growth factor II mRNA-binding protein 1 (IMP1) regulates cellular proliferation and migration. Expression of IMP1 is limited to a few adult human tissues. However, it commonly expresses in a variety of cancers. Our objective was to study the regulatory mechanism of IMP1 on the cellular functions of choriocarcinoma (CC) JAR cells.

Methods

IMP1 protein levels were measured in CC tissues via immunohistochemistry. Specific siRNAs were used to down-regulate gene expressions. The abilities of migration and invasion were estimated by wound-healing and Matrigel chamber assays. The profile of IMP1-binding genes was investigated with an Agilent microarray. RT-qPCR, RNA immunoprecipitation, and IMP1 rescue experiments were performed to confirm the association between IMP1 and its binding genes. Gene expression was further analyzed by using RT-PCR and Western blotting.

Results

Strong IMP1 expressions were frequently detected in CC tissues. Knockdown of IMP1 expression in JAR cells inhibited cell migration and invasion, but did not affect cellular proliferation and morphology. Microarray and RNA-immunoprecipitation results revealed several candidate genes regulated by IMP1. Among them, ribosomal protein S6 kinase (RSK2) and protein phosphatase methylesterase 1 (PPME1) were confirmed to be down-regulated in IMP1-depleted JAR cells. Re-expression of IMP1 into the cells restored the expressions of RSK2 and PPME1. Furthermore, the depletion of RSK2 or PPME1 decreased the migration and invasion of JAR cells.

Conclusion

Our results suggest that IMP1 plays an essential role in the regulation of migration and invasion of human CC cells, possibly through the novel effectors RSK2 and PPME1.