铁死亡相关机制与子宫内膜癌

子宫内膜癌是女性生殖系统三大恶性肿瘤之一,严重危害女性健康。近年研究发现,铁死亡在子宫内膜癌的发生、发展中起到重要作用。作为一种细胞程序性死亡方式,铁死亡与铁代谢、脂质代谢和氧化应激等生物过程密切相关。研究发现通过调控子宫内膜癌细胞铁代谢及氧化应激,可以促进癌细胞铁死亡,抑制肿瘤细胞增殖,且调控铁死亡的相关通路可以影响子宫内膜癌患者化疗敏感性,分析铁死亡相关基因表达可以预测子宫内膜癌患者预后。因此,铁死亡通路相关蛋白有望成为子宫内膜癌治疗新靶点。综述铁死亡的发生机制及其在子宫内膜癌的发生、治疗中的作用,并分析铁死亡相关分子作为一种新型的分子分型预测子宫内膜癌预后的潜在应用价值,为铁死亡在子宫内膜癌治疗领域中的应用提供新思路。     

Unexpected uterine smooth muscle tumor of uncertain malignant potential and sarcoma: A single center cohort study in South Korea

ObjectiveTo evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation.Material and methodsData were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017.ResultsA total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785).ConclusionThe risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.     

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset

ObjectiveRecent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS).MethodsArchival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed.ResultsSomatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively).ConclusionPPP2R1A mutations might have a role in dismal prognosis of advanced EC.     

Clinicopathologic and protein markers distinguishing the “polymerase epsilon exonuclease” from the “copy number low” subtype of endometrial cancer

ObjectiveThe need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (POLE) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish the POLE from the copy number (CN)-low subtype in EC.MethodsNinety-one samples (15 POLE, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort.ResultsBody mass index (BMI) and tumor grade were significantly associated with the POLE subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the POLE from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the POLE than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683.ConclusionBMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the POLE from the CN-low subtype. Cyclin B1 IHC may replace POLE sequencing in molecular classification of EC.     

黏液瘤病毒作用PI3K/AKT通路诱导子宫内膜癌细胞凋亡

目的 探讨黏液瘤病毒（MV）对子宫内膜癌HEC-IB细胞凋亡和增殖的作用.方法 通过荧光染色等观察细胞核固缩和染色体碎片等形态学变化,MTT法测定MV对HEC-IB细胞的生长抑制作用,采用流式细胞仪和免疫印迹实验检测HEC-IB细胞的生长凋亡情况及其相关蛋白的表达变化.结果 MV对子宫内膜癌HEC-IB细胞具有明显的生长抑制作用,并能诱导细胞发生凋亡,随着作用时间的延长,细胞的生长抑制率及细胞凋亡率均明显升高.MV抑制细胞生长及诱导细胞发生凋亡的过程中,细胞磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B（AKT）、糖原合酶激酶3（GSK3）表达水平及活性显著降低.结论 MV能够通过多条信号途径促进人子宫内膜癌HEC-IB细胞发生凋亡,通过抑制PI3K/AKT的活性是其体外诱导人子宫内膜癌HEC-IB细胞发生凋亡和抑制增值的重要作用机制.     

中晚期子宫内膜癌术后放疗效果的系统评价

目的系统评价术后放疗在中晚期子宫内膜癌的治疗效果、安全性及成本效果。方法电子检索Cochrane图书馆、The Cochrane Central Register of Controlled Trials（CENTRAL）、The National Research Register、Health technology assessment database（HTA）、MEDLINE、EMbase、CancerLit、CBMdisc、VIP、万方学位论文数据库、CNKI并辅以手工检索。检索时间截至2007年3月，收集子宫内膜癌（EC）术后放疗与术后非放疗比较的随机对照试验（RCT）。由两名研究者按Cochrane系统评价方法，独立选择试验，提取资料、评价纳入研究的方法学质量，提取有效数据进行Meta分析。结果共纳入符合标准的RCT3个，患者1126例，3个RCT均是术后盆腔放疗与术后化疗的比较，其中2个RCT为放疗与CAP化疗方案比较，包括730例患者；1个RCT为放疗与AP化疗方案比较，包括396例患者。Meta分析结果显示：对子宫内膜癌Ⅰc、Ⅱ、Ⅲ期患者，其5、7年总体生存率、疾病无进展存活率及5年局部复发率、远处复发率、总复发率，在放疗组与化疗组的差异无统计学意义；对子宫内膜癌Ⅲ、Ⅳ期患者，其5年总体生存率、疾病无进展存活率，化疗组优于放疗组；在3／4级消化系统及泌尿生殖系毒性反应方面，化疗组与放疗组的差异无统计学意义；而3／4级血液学毒性反应方面，化疗组高于放疗组。结论对子宫内膜癌Ⅰc、Ⅱ、Ⅲ期患者，术后盆腔放疗的效果和化疗相似；但对子宫内膜癌Ⅲ、Ⅳ期患者，放疗的效果比化疗差；放疗的骨髓抑制作用比化疗小，在胃肠道和泌尿生殖系3／4级毒性反应，两者差异无统计学意义。     

子宫内膜癌组织中内皮抑素的表达及与血管形成的关系

目的:探讨内皮抑素(Endostatin)在子宫内膜样腺癌组织中的表达及其与肿瘤血管形成的关系.方法:应用免疫组织化学方法(MaxVision法)检测66例子宫内膜样腺癌组织及26例增生期子宫内膜组织中内皮抑素的表达及CD34标记的MVD.结果:内皮抑素和MVD在子宫内膜样腺癌组织中高表达(P<0.01),与子宫内膜样腺癌分期有关(P<0.05).结论:内皮抑素检测可作为评价子宫内膜样腺癌生物学参数的参考指标之一.     

Endometriosis-associated endometrioid adenocarcinoma of the fallopian tube synchronized with endometrial adenocarcinoma: A case report

BACKGROUND Endometriosis is a common gynecological disorder that affects women of reproductive age. It is characterized by a cancer-like invasion of the extra-uterine endometrium and exhibits a strong association with ovarian clear cell cancer and endometrioid cancer. Endometriosis-associated fallopian tube endometrioid adenocarcinoma synchronized with endometrial adenocarcinoma was rarely reported.CASE SUMMARY A 49-year-old woman was referred to our hospital complaining about abnormal vaginal b...     

绝经后子宫内膜癌患者彩超检验结果分析

目的:综合分析彩超判断子宫内膜厚度在绝经后妇女子宫内膜癌中的诊断效果。方法:在2014年8月至2016年8月选取我院收治的120例绝经后阴道出血妇女患者临床资料作为研究对象,其中有30例子宫内膜癌患者(A组)、30例子宫内膜增生患者(B组)、30例子宫内膜炎患者(C组)以及30例正常子宫内膜患者(D组)。分析四组患者的平均子宫内膜厚度、内膜均匀厚度以及血流特征等参数指标。结果:A组患者子宫内膜厚度显著高于B、C、D三组患者(P0.05);A组患者与B、C、D三组患者的内膜均匀程度比较无统计学意义(P0.05);A组患者血流特征≤4的比例显著高于B、C、D三组患者(P0.05)。结论:彩超判断子宫内膜厚度在绝经后妇女子宫内膜癌中的诊断效果比较高。     

多参数MRI及PET在子宫内膜癌的应用进展

子宫内膜癌(EC)是发生于子宫内膜的一组上皮性恶性肿瘤,为女性生殖系统三大恶性肿瘤之一,好发于围绝经期和绝经后女性,常伴随不规则阴道出血。术前准确分期对选择治疗方案和改善预后至关重要。多参数MRI(如DCEMR、DWI、MRS)及PET/CT、PET/MR在EC的术前诊断、肿瘤分期及术后评估中各具优势。本文围绕MRI及PET对EC的研究进展进行综述。