NF-κB信号通路与子宫内膜癌关系的研究进展

NF-κB信号通路是一个复杂的网络,该通路的异常激活可导致肿瘤相关基因的异常表达,在肿瘤的发生、发展中起着抑制细胞凋亡、促进细胞增殖、促进肿瘤转移的重要作用。目前研究表明,该信号通路与子宫内膜癌细胞凋亡、增殖、侵袭、转移、血管生成及治疗有关。本文就NF-κB信号通路与子宫内膜癌关系的研究进展做一综述。     

端粒酶逆转录酶与子宫内膜癌的研究进展

人端粒酶逆转录酶(hTERT)是端粒酶的核心组分,与包括子宫内膜癌在内的多种肿瘤的发生、发展密切相关。hTERT表达和端粒酶活性增高可以促进肿瘤的发生。检测hTERT表达和端粒酶活性有助于子宫内膜癌的诊断。调控hTERT转录,抑制端粒酶活性有望成为治疗子宫内膜癌的新方法。现将hTERT与子宫内膜癌的研究进展作一综述。     

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。     

脂联素与子宫内膜癌发生发展的关系研究

脂联素是一类由脂肪细胞分泌,具有调节能量代谢、胰岛素增敏、促进抗炎作用的脂肪因子。近年发现,脂联素在子宫内膜癌的发生发展中起着重要作用。其可通过AMPK/LKB1/ERK、JAK2/STAT3等通路直接抑制子宫内膜癌细胞生长并促其凋亡,也可间接通过胰岛素增敏、改变炎症因子水平、抑制肿瘤新生血管形成抑制子宫内膜癌的发生发展。本文就脂联素在子宫内膜癌发生发展过程中的作用做一综述。     

糖代谢异常与子宫内膜癌关系的研究进展

机体糖、脂及蛋白质代谢异常导致的糖尿病、肥胖和高血压是子宫内膜癌发病的高危因素,代谢紊乱性疾病发生发展的各个环节与子宫内膜癌的发病机制密切相关,两者存在共同的激素水平异常及代谢酶类和细胞因子的表达异常。其中,糖代谢异常的可能致病基础胰岛素抵抗导致多种肿瘤的发生发展,其与子宫内膜癌发病的关系也日益受到重视。通过改善机体糖代谢状况,治疗糖尿病以及控制体质量等提高内膜癌治愈率,成为指导预防及治疗内膜癌的有效手段。     

肿瘤相关成纤维细胞在子宫内膜癌中的研究进展

肿瘤微环境（tumor microenvironment,TME）中不同类型细胞的相互作用在子宫内膜癌（endometrial cancer）的发生、发展中起到了关键作用。其中肿瘤相关成纤维细胞（cancer-associated fibroblasts,CAFs）作为TME的重要组成部分,通过直接或间接作用的方式调控子宫内膜癌细胞的恶性生物学行为,促进肿瘤进展。研究表明CAFs参与调节子宫内膜癌细胞的增殖、迁移、侵袭和代谢等途径,同时在TME的基质重塑、血管生成和免疫调节等方面发挥着重要作用。以CAFs为靶点的临床试验研究打破了子宫内膜癌传统治疗手段的局限性,为终末期子宫内膜癌患者带来了新的治疗选择,然而仅有部分患者获益,其中CAFs的来源及功能异质性与治疗抵抗密切相关。综述CAFs在子宫内膜癌中的研究进展,以深入了解CAFs的特性及功能,为子宫内膜癌的诊治提供新的思路。     

PI3K/PKB信号传导通路与子宫内膜癌研究进展

磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(PKB)信号通路是许多生长因子、细胞因子等的下游信号传导通路,通过抑制细胞凋亡,促进细胞生长、增殖、迁移、侵袭和肿瘤血管生成而与肿瘤发生发展密切相关。许多与子宫内膜癌相关的因素通过PI3K/PKB通路参与肿瘤发生发展,这为子宫内膜癌病因学研究及寻找新的治疗靶点提供了新思路。     

P13K／PKB信号传导通路与子宫内膜癌研究进展

磷脂酰肌醇3激酶（P13K）/蛋白激酶B（PKB）信号通路是许多生长因子、细胞因子等的下游信号传导通路，通过抑制细胞凋亡，促进细胞生长、增殖、迁移、侵袭和肿瘤血管生成而与肿瘤发生发展密切相关。许多与子宫内膜癌相关的因素通过P13K／PKB通路参与肿瘤发生发展．这为子宫内膜癌病因学研究及寻找新的治疗靶点提供了新思路。     

PI3K/PKB信号传导通路与子宫内膜癌研究进展

磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(PKB)信号通路是许多生长因子、细胞因子等的下游信号传导通路,通过抑制细胞凋亡,促进细胞生长、增殖、迁移、侵袭和肿瘤血管生成而与肿瘤发生发展密切相关.许多与子宫内膜癌相关的因素通过PI3K/PKB通路参与肿瘤发生发展,这为子宫内膜癌病因学研究及寻找新的治疗靶点提供了新思路.     

Matriptase与子宫内膜癌侵袭转移相关性的研究进展

侵袭和转移是恶性肿瘤的重要生物学特征之一,也是造成肿瘤患者死亡的主要原因。肿瘤的侵袭和转移是一个复杂的病理过程,涉及多种蛋白酶,包括基质金属蛋白酶和丝氨酸蛋白酶等。近来研究发现一种Ⅱ型跨膜丝氨酸蛋白酶Matriptase可通过激活尿激酶型纤溶酶原激活物、肝细胞生长因子/扩散因子、蛋白酶活化受体2和前列腺蛋白酶原促进肿瘤细胞的侵袭和转移,与多种恶性肿瘤,如乳腺癌、食管癌、前列腺癌、宫颈癌、卵巢癌、子宫内膜癌等的发生、发展密切相关。因而Matriptase有望成为恶性肿瘤一个新的诊断和治疗靶标。综述Matriptase与子宫内膜癌侵袭转移的相关性。     

妇科常见恶性肿瘤中自噬的研究进展

妇科恶性肿瘤是女性常见的恶性疾病之一,严重影响女性的健康,主要包括宫颈癌、子宫内膜癌、卵巢癌、阴道癌和外阴癌五大主要类型。其中,以宫颈癌、子宫内膜癌和卵巢癌最为常见。治疗妇科肿瘤的方法通常包括手术、放疗和化疗。然而,其高患病率和高致死率以及对化疗耐药严重制约着妇科肿瘤治愈率的提高。近年来,随着对肿瘤研究的不断深入,另一种细胞死亡的生物学过程——自噬现象,逐渐受到重视。自噬对肿瘤的发生、发展具有非常重要的作用。此外,肿瘤细胞可以通过自噬增强其对化疗药物的敏感性。卵巢癌、子宫内膜癌及宫颈癌等常见妇科恶性肿瘤组织中都存在自噬现象。自噬为妇科肿瘤的治疗提供了一种新思路。通过对自噬反应的干预,有可能成为妇科肿瘤生物治疗中的新方向。     

子宫内膜癌中肿瘤干细胞的研究进展

子宫内膜癌是妇科常见的三大恶性肿瘤之一,严重影响女性的生活和健康。现行的治疗手段主要包括手术、放射治疗(放疗)和化学治疗(化疗),但对放疗或化疗后复发病例的治疗,仍是极大的挑战。肿瘤干细胞是一类存在于肿瘤组织中具有自我更新能力和多向分化潜能的肿瘤细胞亚群,目前肿瘤干细胞的研究方兴未艾。在子宫内膜癌发病机制的研究中,大量研究证实具有干细胞潜能的稀有的子宫内膜癌肿瘤细胞在疾病发生、发展、转移和复发中起关键作用。就肿瘤干细胞的性质、来源做一总结,并对子宫内膜癌中肿瘤干细胞存在的证据及其标记物的研究进展作一综述。     

Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors

BACKGROUND: A high level of estrogen receptor-alpha (ER-alpha) is believed to be favorable in the prognosis and treatment of endometrial, ovarian, and breast cancer. High levels of ER-alpha have been shown to inhibit the growth and invasive, metastatic potential of breast cancer cell lines. To bring about these inhibitory effects, ER-alpha probably acts through other cellular factors involved in the regulation of cell growth. OBJECTIVE: To investigate the role of high levels ER-alpha in growth inhibition of endometrial cancer cells. METHODS: A human ER-alpha cDNA was stably overexpressed in an endometrial cancer cell line, namely, Ishikawa. ER-alpha-overexpressing, parent, and control Ishikawa cells were grown in vitro and their growth rates were compared by cell count. ER-alpha-overexpressing and parent Ishikawa cells were also grown in vitro as tumors in a chicken chorioallantoic membrane (CAM) model, and tumor growth and angiogenesis was measured. Finally, levels of angiogenesis-modulating factors, nitric oxide synthase (NOS), and vascular endothelial growth factor (VEGF) were examined in relation to ER overexpression. RESULTS: The growth of Ishikawa cells was found inhibited in culture as well as in the CAM model. Angiogenesis of CAM tumors was also found inhibited in ER-overexpressing cells. Angiogenic factor VEGF was inhibited whereas the activity of NOS was found elevated following ER overexpression. CONCLUSION: Our work on the Ishikawa cell line indicates that high levels of ER-alpha in endometrial cancer may inhibit cancer growth by modulating angiogenic factors, thereby limiting the blood supply to the growing tumor. Our results support the earlier data from other groups that have shown a positive correlation between high ER content and better prognosis of endometrial cancers.     

RUNX3在妇科肿瘤中的研究进展

宫颈癌、子宫内膜癌和卵巢癌是妇科最常见的三大恶性肿瘤,严重威胁女性的生命安全.DNA甲基化是重要的表观遗传学机制之一,可导致抑癌基因的沉默,最终促成肿瘤的发生.RUNX3是目前抑癌基因研究的热门之一,在细胞生长、增殖、分化、凋亡和信号转导中有着重要作用.RUNX3启动子甲基化会导致其表达沉默,在妇科肿瘤的发生发展中有着...     

肿瘤干细胞与子宫内膜癌的关系研究进展

子宫内膜癌是妇科常见的三大恶性肿瘤之一,其发病率近年来呈上升趋势,严重威胁女性健康。对其发病机制和分型的深入研究旨在寻找一种新的有效的治疗方式,其中肿瘤干细胞学说的提出为肿瘤治疗提供了新途径。肿瘤干细胞是一类具有自我更新、无限增殖、多向分化潜能及高致瘤性的肿瘤细胞亚群。已有大量的研究证实肿瘤干细胞在子宫内膜癌的发生、发展、转移及复发中发挥关键作用,可能是导致子宫内膜癌治疗失败的原因。根据子宫内膜癌肿瘤干细胞表面特异性标志物(如CD133、CD44等)或用细胞生物学特性(如侧群细胞法)进行分离鉴定;此外,也可利用子宫内膜癌肿瘤干细胞高表达乙醛脱氢酶1(ALDH1)及Musashi-1,识别出肿瘤组织中的肿瘤干细胞,使针对肿瘤干细胞的相关靶向治疗成为可能。现就肿瘤干细胞的特性、来源及其与子宫内膜癌相关特殊表面标志物的研究进行综述。     

Immunological factors and their role in the genesis and development of endometriosis

The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation.     

Role of Toll-like receptors in cervical,endometrial and ovarian cancers: A review

Objective

The Toll-like receptors (TLRs) have been implicated in inflammation, innate immunity and cancer. The goal of this paper is to review the available published research about Toll-like receptors and their roles in gynecologic malignancies.

Methods

A Medline search was conducted and published articles from the late 1990s to the present (2014) were reviewed using search phrases, Toll-like receptors and cervical, endometrial and ovarian cancers.

Results

TLR4 and TLR5 are commonly absent in normal cervix, however TLR5 expression is strong in high grade cervical dysplasia as well as invasive cancer. The expression of TLR3 and TLR4 is low in endometrial cancer. TLR2, TLR3, TLR4 and TLR5 are highly expressed in normal and neoplastic ovarian epithelium. TLR3 has been shown to have a dual function: it can contribute to tumor elimination by upregulation of interferons α and β (INF) and natural killer cell (NK) activation or it can indirectly contribute to tumor progression.

Conclusions

Inflammation is an essential element in tumorigenesis. Toll-like receptors can trigger an inflammatory response and cell survival in the tumor micro-environment. TLRs are critical immunomodulators that may play an important role in the development of gynecologic cancers. Currently TLR agonists are being investigated for a potential role as an adjuvant in the treatment of gynecologic malignancies.