Endometrial cancer (EC) is a common gynecological malignancy and its mortality has been increasing in the last twenty years. A growing body of evidence suggests that circulating tumor cells (CTCs) may provide a more complete tumor profile, facilitate the understanding of the molecular mechanism and individual management of EC patients. In this review, we presented the presence and clinical applications of CTCs and disseminated tumor cells (DTCs) in EC, particularly for EC prognosis and management, also highlighted the diagnostic value of tumor cells in urine of EC patients, aim to help researchers better focus on their study in this field.
Nectin-3 and nectin-4 belong to the immunoglobulin (Ig) superfamily, and are Ca2+ -independent homophilic cell adhesion molecules. Nectin-3 is ubiquitous in adult tissues, and it enhances normal levels of synaptic formation. In contrast, nectin-4 is weakly-to-moderately expressed in normal human tissues. In recent years, studies have shown that nectin-3 is highly expressed in the nervous system. Moreover, it is associated with poor prognostic factors in distant metastases and malignant tumors with high vascular invasion such as pancreatic, lung and breast cancers. In particular, nectin-4 is overexpressed in various malignant tumors, and it is associated with proliferation, angiogenesis, metastasis, drug resistance, tumor relapse, DNA repair, cancer stemness, and poor prognosis. Unlike nectin-3, nectin-4 has become a potential prognostic biomarker and specific therapeutic target for cancer as there is no consensus on the significance of abnormal expression of nectin-3 in various cancers.
铁死亡是一种不同于自噬、凋亡和坏死的新型细胞死亡方式,通过细胞铁过载和脂质过氧化启动.近年来,越来越多的研究探索铁死亡相关机制在卵巢癌中的作用,发现改变卵巢癌细胞内铁和脂质的代谢,以及P53、Yes相关蛋白(Yes-associated protein,YAP)和基于PDZ结合基序的转录共激活因子(transcriptional co-activator with PDZ-binding motif,TAZ)的表达可以调控癌细胞铁死亡,进而影响卵巢癌进展.研究还证实铁死亡不仅可以提高卵巢癌细胞对铂类药物的敏感性,增强化疗效果,而且可以改善卵巢癌细胞对多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂的耐药性,提高卵巢癌患者PARP抑制剂治疗的临床获益,而PARP抑制剂与免疫治疗又能促进卵巢癌细胞铁死亡,表明铁死亡与化疗、PARP抑制剂和免疫治疗在抑制卵巢癌细胞生长方面具有协同作用,铁死亡可能成为未来卵巢癌治疗的一个新靶点.
子宫内膜血管肉瘤是一种临床比较罕见的间质性肉瘤,其临床症状不典型,诊断相对困难,确诊主要依据组织活检,目前尚无标准的治疗方案.报道1 例子宫内膜血管肉瘤患者的诊治情况.患者因阴道异常出血 1个月余就诊,期间出血量多于平时月经量.入院后完善专科查体、妇科超声及盆腔磁共振成像等检查,综合外院诊断性刮宫子宫内膜病理切片,考虑子宫内膜肉瘤.行广泛性子宫切除术+双侧附件切除术+盆腔淋巴结切除术+腹主动脉旁淋巴结活检术.术后病理示子宫内膜血管肉瘤,临床分期ⅢC1 期,术后患者未行辅助治疗,术后 5 个月复查考虑复发转移.子宫内膜血管肉瘤术后复发时间短且具有远处转移的风险,术后辅助性放化疗、免疫治疗及靶向治疗可以提高患者的存活率.
Lynch syndrome(LS), an autosomal dominant genetic disorder caused by mismatch repair gene defects, is characterized by the susceptibility to multi-system malignancies. LS associated endometrial cancer(LS-EC) is the most common extraintestinal sentinel cancer of LS. In the era of precision medicine, early screening of LS-EC is of great significance to preventing the occurrence of other LS related malignant tumors. This paper reviews the research progress on screening methods and prevention of LS-EC, in order to provide reference for precise diagnosis and prevention of LS-related tumors.
报告1例较罕见的同时性宫颈腺癌合并卵巢癌双原发癌的病例.该患者为56岁女性,临床主要表现为异常阴道出血和下腹痛,血清肿瘤标志物水平显著升高,盆腔CT示子宫后壁片状强化减低,电子阴道镜下取活检示部分腺上皮高级别上皮内瘤变,不除外更重病变.该患者于2020年6月2日在气管插管全身麻醉下行开腹探查术+子宫扩大切除术+双侧附件切除术+盆腔粘连松解术+盆腔淋巴结清扫术+腹腔引流术,术后行6次化疗及1次盆腔三维适形调强放疗,后因肿瘤复发导致肠梗阻去世.复习国内外报道的宫颈癌合并卵巢癌双原发癌的病例资料,以期提高临床医生对妇科双原发肿瘤的认识.
目的 探讨艾拉光动力疗法(ALA-PDT)治疗子宫颈上皮内瘤变(CIN)的临床效果及其安全性.方法 收集2020年8月至2021年8月在兰州大学第一医院宫颈疾病中心接受ALA-PDT治疗的38例CIN患者的临床资料,分析ALA-PDT的治疗效果、不良反应及预后.结果 患者在经ALA-PDT治疗前人乳头瘤病毒感染率为92.1%,治疗后感染率为48.6%,随访期间无病例复发.所有接受治疗的患者均可耐受光照,8例治疗后出现分泌物增多、下腹坠胀、局部不适、灼烧感等,无远期不良反应发生.结论 ALA-PDT治疗CIN安全、有效且可重复性高,尤其适用于年轻且有生育要求的CIN患者.
二甲双胍是公认治疗2型糖尿病(T2 DM)的一线药物,近年来,多项研究表明二甲双胍在包括子宫内膜癌(EC)、宫颈癌(CC)和卵巢癌(OC)等在内的多种恶性病变中具有抗肿瘤作用,从而提高妇科恶性肿瘤患者术后生存期.因此,深入探讨二甲双胍在妇科恶性肿瘤中的潜在作用对临床恶性肿瘤的辅助治疗具有重要意义.本文通过查阅大量文献,阐述其在不同妇科恶性肿瘤中的作用机制及应用疗效,为临床妇科恶性肿瘤治疗提供借鉴.
子宫破裂是一种严重的、危及孕产妇及新生儿生命的不良产科事件,具有极高的大出血率和死亡率.子宫破裂主要的危险因素是瘢痕子宫,既往无子宫手术史的孕妇发生子宫破裂极其罕见.本文报道1例罕见的非瘢痕子宫妊娠子宫不完全性破裂的病例,对其病情发展及诊治经过进行整理,并对相关文献进行复习,分析该类孕妇的临床特征,以期提高临床医生对此类疾病的警惕性,做到及早发现和及早干预,避免不良围产结局的发生.
Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein–protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a “drug component–target gene–disease” network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.
子宫脂肪平滑肌瘤是子宫肌瘤的一种特殊类型,由不同比例的成熟平滑肌细胞、脂肪细胞和纤维组织组成.其病因及发病机制不明确,仅有几种普遍接受的理论可以解释,包括错位胚胎脂肪细胞的成脂细胞分化、结缔组织或平滑肌纤维向脂肪细胞的化生以及多能干细胞沿子宫神经和血管的迁移和脂肪浸润.其临床表现及一般检查、影像学检查均无特异性,目前诊断主要靠术后病理诊断.由于其发生率低,目前研究较少,未建立起规范化治疗指南,无症状者可加强监测,有症状者可行手术治疗,包括经腹腹腔镜、宫腔镜子宫肌瘤切除术,以及经腹腹腔镜或开腹或阴道下行或不行双侧附件切除术的全子宫切除术,手术方式取决于肿瘤大小、位置、数量、患者要求和可用的手术设施.大多数脂肪平滑肌瘤预后较好,尚无研究报道子宫脂肪平滑肌瘤的恶变率.因此,研究子宫脂肪平滑肌瘤的生物学机制以及如何选择最佳的个性化治疗方案至关重要.
宫颈癌是女性生殖系统最常见的恶性肿瘤,持续性高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染是导致宫颈上皮内瘤变及癌变的必要因素.目前临床上针对宫颈癌的早期筛查方法有HPV检测、宫颈脱落细胞学和阴道镜检查.临床上多数宫颈癌患者HPV检测结果为HR-HPV阳性,但有不足1%的宫颈癌患者HPV检测结果为HR-HPV阴性.与HR-HPV阳性宫颈癌患者相比,多数HR-HPV阴性宫颈癌患者的预后较差.因此寻找HR-HPV阴性宫颈癌的发病机制、探索特异性生物标志物及新的治疗靶点成为目前最为迫切的问题.综述HR-HPV阴性宫颈癌的发病原因、临床特征及分子生物学研究,以期为HR-HPV阴性宫颈癌的诊疗提供新的临床思路及依据.
随着癌症发病的年轻化,患有子宫内膜癌的育龄期女性越来越多.为了保留生育能力,大部分患者倾向于保守治疗.故而众多研究者提出了子宫内膜不典型增生和早期子宫内膜癌的保守治疗方案,并在临床上进行了小样本研究.传统治疗以口服大剂量孕激素为主,然而多数口服孕激素治疗的患者复发率高、并发症多.左炔诺孕酮宫内缓释节育系统通过局部作用于子宫内膜,可减少大量孕激素对机体造成的不良反应.宫腔镜能够精准切除病灶,保护正常子宫内膜,相对降低了发生不孕、流产风险.二甲双胍的抗肿瘤作用能增加孕激素的有效率.通过综述子宫内膜不典型增生和早期子宫内膜癌各种保守治疗后的缓解率、复发率和妊娠结局,为临床上在治疗前对每位患者的自身因素及疾病特点进行评估,以采取对患者最有益的治疗方案及管理模式提供依据.
卵巢癌是恶性程度最高的妇科恶性肿瘤.近年来,组蛋白修饰(histone modifying enzymes,HMEs)作为表观遗传修饰的重要部分在卵巢癌中被广泛研究,包括组蛋白甲基转移酶及去甲基酶、组蛋白乙酰转移酶及去乙酰化酶在内的多种组蛋白修饰酶通过对组蛋白及非组蛋白进行修饰,在卵巢癌细胞的增殖、迁移等方面发挥了重要作用,并且能够调控化疗耐药的发生.多种组蛋白修饰酶的抑制剂通过促进细胞生长停滞及凋亡、抑制肿瘤细胞的侵袭、增加化疗敏感性等在卵巢癌中发挥良好的抗肿瘤作用,有望成为卵巢癌精准治疗的新策略.本文将针对参与甲基化及乙酰化过程的组蛋白修饰酶在卵巢癌中的作用机制及治疗潜力作一综述.
管状绒毛状腺瘤是一种常见于胃肠道的易发生恶变的良性肿瘤.原发性阴道管状绒毛状腺瘤较罕见,其病理学特征与胃肠道腺瘤相似,且易复发.其临床症状不典型,易误诊,确诊主要依据组织活检.此类病例发病率较低且报道较少,因此目前尚无标准的诊断与治疗方法.报道1例原发性阴道管状绒毛状腺瘤伴局部癌变,回顾该患者的临床表现、影像学特征及病理特征,并查阅大量文献,总结其特点,以提高临床医师对该病的认知.
Cervical cancer is the most common gynecological malignancy in developing countries. Scholars at home and abroad call cervical cancer younger than 35 years old as cervical cancer in young women (referred to as young cervical cancer). In recent years, with the promotion of cervical cancer screening, the incidence of young cervical cancer has gradually increased. This case reports a 17-year-old teenager with stage IV cervical squamous cell carcinoma with human papillomavirus type 16 and 18 positive and abnormal lipid metabolism. The onset is early, the clinical symptoms are typical, the disease progresses rapidly, and the prognosis is poor. Review the patient’s family history, morbidity, sexual life history and related clinical examination indicators, and consult relevant literature to find factors related to the onset of cervical cancer, and summarize the characteristics of the case to improve clinicians’ awareness and clinical diagnosis of the disease, And at the same time discuss whether the initial screening age for special populations should be treated specially.
Purpose: To investigate the anticancer effects of cisplatin (DDP) in combination with matrine on cervical cancer U14 cell tumor-bearing mice. Methods: The cell proliferation of cervical cancer U14 cells treated with DDP (25, 20, 15, 10 and 5 μg/mL); matrine (2.5, 2.0, 1.5, 1.0 and 0.5 mg/mL); or DDP (15 μg/mL) + matrine (2.5, 2.0, 1.5, 1.0 and 0.5 mg/mL) was determined with MTT assay. The anticancer effect of DDP + matrine in U14 tumor-bearing mice was also investigated, based on expression of tumor suppressor lung cancer 1 (TSLC1) using quantitative real time-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Results: The inhibition of proliferation of U14 cells ranged from 26.68–70.25, 10.20–61.73, and 51.89–89.75 % for DDP, matrine and DDP + matrine, respectively. In mice with U14 solid tumors, the DDP group had 12.3 % weight loss (p < 0.05). Treatment with DDP, matrine, and DDP + matrine reduced tumor growth by 64.56, 42.22–56.67, and 67.78–81.11 %, respectively (p < 0.01). Results from RT-qPCR and immunohistochemistry showed corresponding increases in expression levels of TSLC1. Conclusion: These results indicate that the anticancer activity of DDP + matrine is higher than that of a single treatment with either DPP or matrine. The likely mechanism of action might be related to promotion of TSLC1 expression. This finding provides a potential strategy for the management of cervical cancer.
Synaptic cell adhesion molecules (SynCAMs) are single transmembrane proteins that belong to the immunoglobulin superfamily of cell adhesion molecules. In the present study, a decrease in SynCAM levels in ovarian tumor tissues compared with normal tissues is reported; the downregulation was accompanied by the grade malignancy. The observations suggested that SynCAM may be essential for important novel functions in ovarian cancer. Further experiments showed that low SynCAM expression inhibited membrane palmitoylated protein 6 (MPP6) expression, a member of the palmitoylated membrane protein subfamily of peripheral membrane-associated guanylate kinases. In addition, low levels of MPP6 in ovarian tumor tissues correlated with shorter patient survival. A SynCAM-regulated pathway may provide molecular targets for the treatment of ovarian cancer and novel biomarkers to be used in clinical diagnosis.
Previous studies have shown that cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is frequently inactivated but functions as a tumor suppressor in many solid tumors. However, the characterization of CADM1 expression in ovarian cancer cells and the mechanisms of its tumor suppressor function are not fully understood. We generated ovarian cancer cell lines in which CADM1 was stably upregulated or downregulated. CADM1 expression was significantly decreased in ovarian cancer tissue and cells lines. Functionally, knockdown of CADM1 promoted the growth, migration and invasion of ovarian cancer cells. Conversely, further experimental evidence indicated that overexpression of CADM1 inhibited the migration and invasion of ovarian cancer cells potentially through inhibition of the PI3K/Akt/mTOR signaling pathway by regulating upstream regulators (LXR/RXR, IGF1, IFI44L and C4BPA) and downstream effectors (APP, EDN1, TGFBI and Rap1A). In conclusion, CADM1 inhibits ovarian cancer cell proliferation and migration by potentially regulating the PI3K/Akt/mTOR signaling pathway. CADM1 could be a potential therapeutic target for ovarian cancer.
Aim: Research on novel mutant genes may develop the treatment of cervical cancer (CC). The role of miRNA-526b in epithelial-mesenchymal transition (EMT) of CC was investigated. Methods: The role and the molecular mechanism of miRNA-526b in CC and its effect on EMT were analyzed in clinical specimens and oncology experiments. Results: miRNA-526b was proved to be decreased in CC and associated with malignant clinicopathological characters. The character of miRNA-526b in EMT was also inspected in CC cells and tumor models. miRNA-526b was found to be able to inhibit the EMT property of CC cells by directly targeting PBX3. Conclusion: miRNA-526b restoration may be deliberated as a new treatment strategy of CC.