二甲双胍在早期子宫内膜癌中的应用

近年来子宫内膜癌的发病率逐年升高且有年轻化的趋势.保留生育功能成为越来越多年轻患者的诉求.目前子宫内膜癌保守治疗的主要方法是以孕激素为基础的药物治疗.尽管这种方法在临床上取得一定效果,但仍然面临高复发率、低妊娠率等问题.二甲双胍是一种常用的降糖药,除早期糖尿病病人外,也用于多囊卵巢综合征患者的治疗.近几年有研究者将二甲...     

二甲双胍与子宫内膜癌发病机制关系的研究进展

子宫内膜癌（endometrial carcinoma,EC）以其逐年增加的发病率及病死率成为生殖道三大恶性肿瘤之一,其发病机制及治疗手段的研究受到越来越多研究者的关注。二甲双胍（metformin）最初作为肥胖型糖尿病的治疗药物,近年来被用于子宫内膜癌治疗的思路受到很多基础实验的支持。本文就近年来有关子宫内膜癌发病机制及二甲双胍对其细胞影响的基础实验进行综述,结果显示二甲双胍对子宫内膜癌细胞的增殖、凋亡、迁徙都具有明显的影响,为子宫内膜癌的治疗提供了新的思路。     

二甲双胍在结直肠癌治疗中的研究进展

结直肠癌是常见的胃肠道肿瘤之一,与2型糖尿病等代谢疾病关系密切.二甲双胍作为2型糖尿病防治指南中推荐的一线用药,除了可以降低血糖外,还具有一定的抗肿瘤作用.近年来,二甲双胍在结直肠癌中的研究受到越来越多的关注.二甲双胍不仅可以通过多种机制抑制结直肠癌细胞的增殖、迁移及侵袭,还可以促进其凋亡.此外,它还可以增加结直肠癌对...     

二甲双胍在肿瘤细胞代谢中的研究进展

二甲双胍是2型糖尿病的一线降糖药物,其机制主要通过抑制肝脏葡萄糖的输出,并提高机体外周组织对胰岛素的敏感程度,从而增加葡萄糖的摄取和利用.不仅如此,现在有研究认为二甲双胍还可能通过激活酶的信号系统而发挥多方面的代谢调节作用.近年来二甲双胍表现出了除降糖以外的多种作用,如抗炎、抗肿瘤、延长寿命、预防脱发以及改善肠道菌群失...     

二甲双胍联合醋酸甲地孕酮治疗子宫内膜癌的效果及对患者肿瘤标志物的影响

目的 探讨二甲双胍联合醋酸甲地孕酮治疗子宫内膜癌的效果及对患者肿瘤标志物的影响.方法 依据治疗方式的不同将65例子宫内膜癌患者分为二甲双胍组(n=33,给予二甲双胍治疗)及联合治疗组(n=32,给予二甲双胍联合醋酸甲地孕酮治疗).比较两组患者的临床疗效、血清肿瘤标志物[结缔组织生长因子(CT-GF)、血管生成素-2(A...     

二甲双胍在肿瘤治疗基础研究中的进展

二甲双胍是治疗2型糖尿病的一线药物。临床流行病学研究发现在2型糖尿病患者中, 相较于胰岛素及其他口服降糖药物治疗组, 二甲双胍治疗组的恶性肿瘤发病率和死亡率均显著降低。同时, 基础研究证实在体外培养细胞及体内动物模型中二甲双胍可抑制多种恶性肿瘤细胞的生长。其可能的机制为调节体内胰岛素/IGF-1轴间接抑制肿瘤生长; 直接作用于肿瘤细胞并抑制其生长。这些结果提示二甲双胍具有抗肿瘤的作用, 可能成为恶性肿瘤辅助治疗的新手段之一。      

二甲双胍对子宫内膜癌的抗肿瘤作用及对其生存期的影响

子宫内膜癌是女性最常见的恶性肿瘤之一,过去的十年,其死亡率明显上升,尤其以发展中国家为甚。二甲双胍作为治疗2型糖尿病的一线药物而被大家了解,目前许多研究提供了二甲双胍抗肿瘤作用的证据,并有学者进行小规模的临床研究表明口服二甲双胍可以提高子宫内膜癌患者的生存率,降低复发风险,这些发现均为临床上治疗子宫内膜癌提供了新的思考方向。本文对二甲双胍与子宫内膜癌生存率之间的关系以及其抗肿瘤作用进行综述。     

二甲双胍在肿瘤免疫治疗中的进展和挑战

二甲双胍属于双胍类口服降糖药物,广泛应用于2型糖尿病的治疗。流行病学和临床研究表明,二甲双胍除了具有降血糖作用外,对肿瘤的预防、治疗和预后均有裨益。这使得二甲双胍可能成为癌症预防和治疗的候选药物。免疫检查点抑制剂(ICIs)已成为许多肿瘤的有效治疗手段。新近研究表明,二甲双胍用作ICIs辅助用药可以使某些肿瘤患者获益,这对研究新型免疫治疗模式,提高免疫治疗的疗效,以期取得更持久的生存获益意义重大。本文就二甲双胍改善免疫微环境的机制、二甲双胍辅助ICIs治疗的相关研究进展展开综述,并探讨联合用药的不良反应,以期指导临床用药。     

二甲双胍在乳腺癌中抗肿瘤作用研究进展

临床前研究表明降糖药二甲双胍对乳腺癌有抗肿瘤作用,能降低糖尿病患者乳腺癌发病风险和死亡风险,也能提高乳腺癌患者新辅助化疗后病理完全缓解率。体内外实验表明二甲双胍有效抑制各种乳腺癌细胞和移植瘤,并和化疗药物、HER2靶向药物、新型抗肿瘤药物有良好协同作用。主要分子机制包括全身性下调胰岛素及相关信号通路、肿瘤细胞内激活LKBl／AMPK、抑制下游mTOR通路等。目前各国开展了多个临床试验评估--sp双胍在乳腺癌防治中的应用价值。     

二甲双胍在恶性肿瘤放疗中的应用研究进展

二甲双胍(C4H11N5)是治疗2型糖尿病的主要药物.有研究显示,二甲双胍可以抑制肿瘤生长,改善恶性肿瘤患者的预后.近年越来越多的研究发现,二甲双胍可以改善肿瘤细胞的放疗敏感性.然而,二甲双胍增强恶性肿瘤放疗敏感性的具体机制尚未完全阐明.本研究将对有关二甲双胍联合放疗应用的最新发现进行综述,并着重介绍其在不同肿瘤中的疗...     

维生素D及其受体在妇科癌症中的研究进展

在过去的二十几年中,国内外大量的研究是关于维生素D及维生素D受体(vitamin D receptor,VDR)在癌症发生、发展中所起的作用.维生素D的活性代谢产物1,25(OH)2 D3除了维持体内矿物质的稳态和骨骼的功能外,还具有抑制细胞增殖、诱导细胞分化、凋亡及免疫调节的作用.近些年,越来越多的研究证据表明,维生...     

Predictors for long-term survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers

BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection.     

长链非编码RNA在妇科恶性肿瘤中的研究进展

长链非编码RNA(LncRNAs)是一组转录本长度超过200bp,但很少具有完整蛋白编码功能的RNA。研究者发现这些非编码RNA在表观遗传水平、转录及转录后水平等多个方面发挥着重大调控作用,从而调节机体的多种生理和病理过程。目前已有大量研究表明异常表达的LncRNAs在肿瘤生物学方面起着重要作用,在肿瘤发生中充当原癌基因或抑癌基因的双重角色。近年来,针对妇科恶性肿瘤的LncRNA的报道逐年增多,本文结合国内外最新报道,对妇科恶性肿瘤相关的LncRNA研究情况进行汇总,旨在为妇恶性科肿瘤的诊疗及预后提供新依据与思路。     

Intracavitary brachytherapy in the treatment of gynecologic neoplasms

Modern intracavitary brachytherapy carefully combined with megavoltage external beam radiotherapy is responsible for the high cure rates achieved with radiation treatment of invasive cervical cancers. Pelvic disease recurrence is rare after treatment of patients with tumors <5 cm in diameter, and even patients with massive tumors 8–10 cm in diameter are cured in 30–50% of cases. Inoperable adenocarcinomas of the endometrium and superficial cancers of the vagina are also effectively treated with intracavitary irradiation. The relative radioresistance of the uterus and vagina, physical advantages resulting from exploitation of the inverse square law, and the radiobiological advantages of low dose rate radiation have combined to make intracavitary irradiation a critical tool in the management of many gynecologic neoplasms. J. Surg. Oncol. 1997;66:141–147. © 1997 Wiley-Liss, Inc.     

Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer

Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin. In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice. These findings indicate that hyperglycemia inhibits the anti-cancer effects of metformin in vitro and in vivo. Furthermore, our results suggest that metformin may elicit stronger responses in normoglycemic vs. hyperglycemic patients, highlighting the need for prospective clinical testing in patients without diabetes.     

长链非编码RNA H19在妇科肿瘤中的研究进展

随着研究进展,长链非编码RNAs在疾病中的作用越来越受到重视,成为最新研究热点.其中H19是第一个被发现与癌症密切相关的lncRNA,在胚胎时期高表达,出生后表达减退,而在肿瘤中又重新出现,并积极参与到肿瘤发生发展的各个环节.尽管越来越多的证据支持H19是重要的癌基因之一,但其在肿瘤中的作用一直存在争议.本文综述H19在常见妇科肿瘤领域的研究进展,为妇科常见肿瘤的诊断、治疗及预后评估提供新的依据和方向.     

Gene therapy in gynecological cancer

Gynecological malignancies remain a major source of morbidity and mortality worldwide. In the USA alone, more than 77,000 women are diagnosed annually and over 28,000 die of some form of a gynecological malignancy. Many of these women will fail conventional therapy, leaving few remaining treatment options. Gene therapy presents one possible alternative treatment modality although, unfortunately, it is currently more theoretical than practical. Here, some of the basic science behind gene therapy is reviewed, different delivery systems used to transport the therapeutic gene are discussed, different methods of achieving a therapeutic effect are examined, some of the key trials in ovarian, endometrial, cervical and vulvar cancer research are highlighted and the future of gene therapy is explored.     

Early triple malignancies of the female genital tract: A case report

A case of early triple malignancies originating in the uterine cervix, endometrium and ovary is reported. A 35-year-old Japanese woman was treated for carcinoma in situ of the cervix by laser conization. Fourteen months later she underwent a modified radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy for a diagnosis of endometrial carcinoma and possible ovarian cancer. The histology of the endometrial cancer revealed an adenoacanthoma without myometrial invasion and a coexisting atypical hyperplasia. The ovarian cancer was an endometrioid adenocarcinoma with a benign cystadenoma in the adjacent area, thus giving the diagnosis of simultaneously occurring, independent primary lesions. Becuase peritoneal cytology was negative and no metastasis was observed, each of the endometrial and ovarian cancers was classified as stage la. This case of triple primary malignancies originating from the genital tract is rare. Only 13 previous cases are reported in the literature.     

Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers

Metabolic alterations are increasingly recognized as important novel anti-cancer targets. Among several regulators of metabolic alterations, fructose 2,6 bisphosphate (F2,6BP) is a critical glycolytic regulator. Inhibition of the active form of PFKFB3^ser461 using a novel inhibitor, PFK158 resulted in reduced glucose uptake, ATP production, lactate release as well as induction of apoptosis in gynecologic cancer cells. Moreover, we found that PFK158 synergizes with carboplatin (CBPt) and paclitaxel (PTX) in the chemoresistant cell lines, C13 and HeyA8MDR but not in their chemosensitive counterparts, OV2008 and HeyA8, respectively. We determined that PFK158-induced autophagic flux leads to lipophagy resulting in the downregulation of cPLA2, a lipid droplet (LD) associated protein. Immunofluorescence and co-immunoprecipitation revealed colocalization of p62/SQSTM1 with cPLA2 in HeyA8MDR cells uncovering a novel pathway for the breakdown of LDs promoted by PFK158. Interestingly, treating the cells with the autophagic inhibitor bafilomycin A reversed the PFK158-mediated synergy and lipophagy in chemoresistant cells. Finally, in a highly metastatic PTX-resistant in vivo ovarian mouse model, a combination of PFK158 with CBPt significantly reduced tumor weight and ascites and reduced LDs in tumor tissue as seen by immunofluorescence and transmission electron microscopy compared to untreated mice. Since the majority of cancer patients will eventually recur and develop chemoresistance, our results suggest that PFK158 in combination with standard chemotherapy may have a direct clinical role in the treatment of recurrent cancer.