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Modulating the tumor immune microenvironment as an ovarian cancer treatment strategy. 调节肿瘤免疫微环境作为卵巢癌治疗策略。
Pub Date : 2012-09-01 DOI: 10.1586/eog.12.41
Uciane K Scarlett, Jose R Conejo-Garcia

After more than 30 years of iterations of surgical debulking plus chemotherapy, the need for complementary ovarian cancer treatments has become clear. In the ovarian cancer microenvironment, myeloid immunosuppressive leukocytes, lymphocytes, fibroblasts and endothelial cells, as well as their secreted products, surface molecules and paracrine survival factors, all provide opportunities for novel interventions. The potential of targeting microenvironmental elements in ovarian cancer patients is underscored by recently successful anti-angiogenic therapies. The compartmentalized nature of ovarian cancer, its immunogenicity and its accessibility make it an ideal disease for targeting non-tumor host cells. This review discusses the 'state-of-the-art' of the field, with an emphasis on the potential of modulating the activity of abundant microenvironmental immune cells, which govern both angiogenesis and immunosuppression.

经过30多年的手术减瘤加化疗的迭代,卵巢癌补充治疗的必要性已经变得很明显。在卵巢癌微环境中,髓系免疫抑制白细胞、淋巴细胞、成纤维细胞和内皮细胞及其分泌产物、表面分子和旁分泌生存因子都为新型干预提供了机会。最近成功的抗血管生成疗法强调了靶向卵巢癌患者微环境因素的潜力。卵巢癌的区隔性、免疫原性和可及性使其成为针对非肿瘤宿主细胞的理想疾病。这篇综述讨论了该领域的“最新技术”,重点是调节丰富的微环境免疫细胞活性的潜力,这些微环境免疫细胞控制着血管生成和免疫抑制。
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引用次数: 18
PI3K–AKT–mTOR inhibitors for the systemic treatment of endometrial cancer PI3K-AKT-mTOR抑制剂用于子宫内膜癌的全身治疗
Pub Date : 2012-09-01 DOI: 10.1586/EOG.12.51
D. Church, Romana Koppensteiner, T. Yap, D. Fink, K. Dedes
Advanced and metastatic endometrial cancer (EC) is associated with a poor prognosis, despite the availability of systemic treatments including endocrine therapy and combination cytotoxic chemotherapy. Response rates of systemic treatments are associated with high toxicity, have poor response rates and responses are genenrally short-lived. Recent findings on the molecular aberrations of the subtypes of EC have enabled in vitro and in vivo studies to exploit targeted treatment for this disease. One of the most common molecular aberrations in EC is the PI3K–AKT–mTOR pathway being activated through different mechanisms in both type I and type II ECs. The aim of this review is to summarize the numerous preclinical and clinical studies, and discuss the future directions.
晚期和转移性子宫内膜癌(EC)预后较差,尽管有包括内分泌治疗和联合细胞毒性化疗在内的全身治疗。全身治疗的反应率与高毒性有关,反应率低,反应通常是短暂的。最近关于EC亚型分子畸变的发现使体外和体内研究能够开发针对该疾病的靶向治疗。EC中最常见的分子畸变之一是PI3K-AKT-mTOR通路在I型和II型EC中通过不同的机制被激活。本文综述了大量临床前和临床研究,并讨论了未来的发展方向。
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引用次数: 2
Timing of planned delivery in uncomplicated monochorionic diamniotic twin pregnancies: a review of the literature 无并发症单绒毛膜双羊膜双胎妊娠的计划分娩时机:文献综述
Pub Date : 2012-09-01 DOI: 10.1586/EOG.12.44
K. Flood
Monochorionic diamniotic (MCDA) twins comprise of 20–30% of twin pregnancies; roughly 50% will be undelivered and ‘uncomplicated’ beyond 32 weeks gestation. This review details accumulating data regarding the risk of intrauterine fetal demise (IUFD) in ‘uncomplicated’ MCDA twins and risks associated with prematurity. ‘Uncomplicated’ MCDA twins are at increased risk for IUFD, even when under intensified surveillance in tertiary care centers. The prospective risk of IUFD in uncomplicated MCDA varies among different studies, with reported rates of up to 3.3% at 34 weeks and 2.2% at 36 weeks. If single IUFD occurs, it exposes the surviving co-twin to potential significant morbidity and mortality. It had been suggested that elective preterm delivery would eliminate this risk, but recent evidence of prematurity morbidity are accumulating. With more intensified monitoring from 32 weeks, it is possible that the rate of IUFD is lower than anticipated. We reviewed the data regarding these risks and their contribution to the decision-making process.
单绒毛膜双胎(MCDA)双胞胎占双胞胎妊娠的20-30%;大约50%的孕妇在怀孕32周后将无法分娩,而且“没有并发症”。本综述详细介绍了有关“无并发症”MCDA双胞胎的宫内胎儿死亡(IUFD)风险以及与早产相关的风险的累积数据。即使在三级保健中心加强监测,“非复杂”MCDA双胞胎发生IUFD的风险也会增加。在不同的研究中,无并发症MCDA中IUFD的前瞻性风险有所不同,据报道,34周时的发生率为3.3%,36周时为2.2%。如果发生单个IUFD,则使存活的同卵双胞胎暴露于潜在的显著发病率和死亡率。曾有人建议,选择性早产可以消除这种风险,但最近有关早产发病率的证据越来越多。从32周开始加强监测,IUFD的发生率可能低于预期。我们回顾了有关这些风险及其对决策过程的影响的数据。
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引用次数: 3
’-omics’ technology and human reproduction: reproductomics “组学”技术与人类生殖:生殖组学
Pub Date : 2012-09-01 DOI: 10.1586/EOG.12.48
J. Bellver, M. Mundi, F. Esteban, Sandra Mosquera, J. Horcajadas
The success of assisted reproduction technology is highly dependent on a precise selection of gametes and embryos and determining the best endometrial window for embryo implantation. For many years, morphological criteria have constituted the only way to assess spermatozoon, oocytes, embryos and endometrial samples in order to improve outcomes. However, this approach has reached a ceiling of success and has been related to unacceptably high rates of multiple pregnancies. New technologies have been developed in order to improve the results and reduce risks via better selection of those gametes and embryos with the highest pregnancy potential, and of more favorable endometrial environments for embryo implantation. In addition, these technologies should ideally be objective, accurate, fast and affordable. Lately, the global strategies that are being employed in reproductive medicine include genomic, transcriptomic, proteomic, metabolomic profiling of oocytes, cummulus cells, granulosa cells, embryos, endomet...
辅助生殖技术的成功高度依赖于配子和胚胎的精确选择,并确定胚胎着床的最佳子宫内膜窗口。多年来,形态学标准一直是评估精子、卵母细胞、胚胎和子宫内膜样本以改善结果的唯一方法。然而,这种方法已经达到了成功的上限,并与多胎妊娠率高得令人无法接受有关。为了更好地选择具有最高妊娠潜力的配子和胚胎,以及为胚胎着床提供更有利的子宫内膜环境,从而提高结果和降低风险,新技术已经发展起来。此外,理想情况下,这些技术应该是客观、准确、快速和负担得起的。最近,生殖医学中采用的全球策略包括卵母细胞、卵丘细胞、颗粒细胞、胚胎、子宫内膜的基因组学、转录组学、蛋白质组学、代谢组学分析……
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引用次数: 7
Postpartum hemorrhage caused by uterine artery pseudoaneurysm and uterine rupture after vaginal delivery 阴道分娩后因子宫动脉假性动脉瘤及子宫破裂引起的产后出血
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.33
M. Origoni, C. Gelardi, F. Pasi, S. Salvatore, M. Candiani
A case of massive hemoperitoneum determined by uterine rupture and uterine artery pseudoaneurysm dissection after vaginal delivery, requiring an emergency laparotomy with arterial ligation, is reported. The authors reviewed the published literature, finding 12 cases of uterine artery pseudoaneurysm and associated postpartum hemorrhage after vaginal delivery, but no cases with uterine rupture have ever been published. Diagnosis is based upon imaging, and management options include arterial embolization, arterial ligation and hysterectomy in particularly severe and life-threatening situations. Vaginal bleeding is associated with favorable outcomes and conservative treatment, while the absence of external blood loss seems to be correlated with a worsened prognosis and the need for an invasive treatment option. Uterine artery pseudoaneurysm rupture after vaginal delivery is a very rare condition of life-threatening postpartum hemorrhage, being more frequently associated with cesarean section. Uterine artery pseudoaneurysm dissection should be suspected in any patient presenting with early or delayed postpartum hemorrhage after a vaginal delivery and can be associated with uterine rupture.
本文报道一例阴道分娩后因子宫破裂及子宫动脉假性动脉瘤夹层导致大量腹膜出血,需要紧急开腹并动脉结扎的病例。作者回顾了已发表的文献,发现12例阴道分娩后子宫动脉假性动脉瘤合并产后出血的病例,但未见报道子宫破裂的病例。诊断基于影像,治疗方案包括动脉栓塞、动脉结扎和子宫切除术,特别是在严重和危及生命的情况下。阴道出血与良好的预后和保守治疗相关,而没有外部失血似乎与预后恶化和需要侵入性治疗方案相关。阴道分娩后子宫动脉假性动脉瘤破裂是一种非常罕见的危及生命的产后出血,多与剖宫产术相关。阴道分娩后出现早期或迟发性产后出血的患者应怀疑子宫动脉假性动脉瘤夹层,并可能与子宫破裂有关。
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引用次数: 0
Genetic factors influencing recurrent pregnancy loss: lessons learnt from recent studies 影响复发性流产的遗传因素:从最近研究中吸取的教训
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.32
S. Dasgupta, Aruna Meka, B. M. Reddy
Recurrent miscarriage (RM) is the loss of three or more consecutive pregnancies before the 24th week of gestation. RM occurs chiefly owing to either a problem with the pregnancy or the environment where it implants and further development occurs. A large number of pathological factors have been attributed to the etiology of RM. A number of genetic association studies in different populations, including that of India, have been conducted, yet with no definite conclusions. This review analyzes various genetic association studies that have been conducted based on the underlying immunological, thrombophilic and endocrine factors in RM, and outlines the salient features of the findings and lessons from those, suggesting possible future directions for research in this area.
复发性流产(RM)是指在妊娠24周之前连续三次或更多的流产。RM的发生主要是由于怀孕或其植入和进一步发育的环境问题。大量的病理因素被归因于RM的病因。在包括印度在内的不同人群中进行了一些遗传关联研究,但没有得出明确的结论。本文分析了基于RM潜在的免疫学、亲血栓性和内分泌因素进行的各种遗传关联研究,并概述了这些研究结果的显著特征和教训,提出了该领域未来可能的研究方向。
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引用次数: 0
First-trimester ultrasound volumetry: measurement techniques and potential application in the prediction of pregnancy complications 孕早期超声容量测定:测量技术及其在妊娠并发症预测中的潜在应用
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.37
Kwok-Yin Leung, T. Ma, B. Lau, Min Chen
First-trimester prediction of intrauterine growth restriction (IUGR), preeclampsia (PE), birthweight, aneuploidy, miscarriage, complications in multiple pregnancies and homozygous α0-thalassemia is a challenging and emerging field. Placenta volumes (PV) and embryo volume/fetal volume ratios are correlated with crown–rump length (CRL) or gestational age. Measurement of PV or placental quotient (PV/CRL ratio) is an early method to identify impaired trophoblast invasion and predict subsequent development of IUGR or PE. In early-onset IUGR caused by triploidy, or trisomy 13 or 18, a larger deficit in fetal volume than CRL is observed. Fetal and placental volume measurements may be applied to predict other conditions such as aneuploidy, miscarriage or stillbirth. Standardization of the 3D volumetric methodology is needed to improve reproducibility of measurement. Further studies are required to determine the use of first-trimester volumetry alone or in combination with Doppler ultrasound and other parameters t...
子宫内生长受限(IUGR)、先兆子痫(PE)、出生体重、非整倍体、流产、多胎妊娠并发症和纯合子α0-地中海贫血的早期妊娠预测是一个具有挑战性的新兴领域。胎盘体积(PV)和胚胎体积/胎儿体积比与冠臀长(CRL)或胎龄相关。测量PV或胎盘商(PV/CRL比率)是早期识别受损滋养细胞侵袭和预测IUGR或PE后续发展的方法。在由三倍体或13或18三体引起的早发性IUGR中,胎儿体积的缺陷比CRL更大。胎儿和胎盘体积测量可用于预测其他情况,如非整倍体、流产或死胎。为了提高测量的再现性,需要对三维体积测量方法进行标准化。需要进一步的研究来确定孕早期体积测定单独使用或与多普勒超声和其他参数联合使用。
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引用次数: 1
Precancerous lesions and an emerging model of endometrial serous carcinogenesis: clinical implications 癌前病变和子宫内膜浆液性癌的新模型:临床意义
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.27
O. Fadare, Wenxin Zheng
Endometrial serous carcinomas (ESCs; also known as uterine papillary serous carcinomas) only represent approximately 10% of endometrial carcinomas [1], but are responsible for up to 40% of all deat...
子宫内膜浆液性癌;子宫乳头状浆液性癌(也称为子宫乳头状浆液性癌)仅占子宫内膜癌的约10%[1],但占所有死亡病例的40%。
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引用次数: 0
Looking to the future: developments in preimplantation genetic diagnosis 展望未来:胚胎植入前遗传学诊断的发展
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.28
J. Traeger-Synodinos, G. Kakourou, C. Vrettou, E. Kanavakis
Since the first clinical preimplantation genetic diagnosis (PGD) cycles carried out in 1989, continuous technical improvements have supported progression from what was initially perceived to be an experimental procedure to a widely acceptable alternative to conventional prenatal diagnosis. PGD requires the use of assisted reproductive technology (ART) to create the preimplantation-stage embryo, followed by biopsy to obtain cell(s) for genetic analysis and, finally, transfer of selected embryos to the womb to establish a pregnancy. PGD is an important reproductive option for parents at high risk of transmitting a single-gene or specific chromosomal abnormality to their children (high-risk PGD), supporting the establishment of a healthy pregnancy while precluding possible pregnancy termination. Alternatively, embryos may be tested for ploidy status, a test widely known as preimplantation genetic screening (PGS). PGS is considered to be a lowrisk form of PGD, offered to women of advanced maternal age or couples with poor reproductive history, which aims to select euploid embryos for transfer to improve the implantation and live birth rates after ART. However, low-risk PGD is controversial and constitutes one of the most highly debated topics in reproductive medicine over the last decade, chiefly because it was introduced into routine clinical practice before its clinical benefit was clarified. Reports to date evaluating ART outcomes following PGS have shown contradicting evidence, mainly complicated by the numerous parameters involved in PGS procedures, many of which may introduce bias. It is paramount to resolve this issue and the only way is through large multicenter randomized controlled studies, such as one currently being organized with the support of the European Society of Human Reproduction and Embryology (ESHRE) [1].
自1989年进行第一次临床植入前遗传学诊断(PGD)周期以来,不断的技术改进支持了从最初被认为是实验性程序到被广泛接受的传统产前诊断替代方案的进展。PGD需要使用辅助生殖技术(ART)来创造着床前阶段的胚胎,然后进行活组织检查以获得细胞进行遗传分析,最后将选定的胚胎移植到子宫中以建立妊娠。PGD是将单基因或特定染色体异常遗传给子女(高风险PGD)的高风险父母的重要生殖选择,支持建立健康妊娠,同时排除可能的终止妊娠。另外,也可以对胚胎进行倍性状态测试,这种测试被广泛称为植入前遗传筛查(PGS)。PGS被认为是一种低风险的PGD,提供给高龄产妇或生育史较差的夫妇,目的是选择整倍体胚胎进行移植,以提高ART后的着床率和活产率。然而,低风险PGD是有争议的,并且在过去十年中构成了生殖医学中最具争议的话题之一,主要是因为在其临床益处被澄清之前,它被引入了常规临床实践。迄今为止评估PGS后ART结果的报告显示了相互矛盾的证据,主要是由于PGS程序中涉及的众多参数而复杂化,其中许多参数可能会引入偏倚。解决这一问题至关重要,唯一的方法是通过大型多中心随机对照研究,例如目前在欧洲人类生殖与胚胎学会(ESHRE)的支持下组织的研究[1]。
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引用次数: 2
Germline stem cells: new insights into female infertility management 生殖系干细胞:对女性不育管理的新见解
Pub Date : 2012-07-01 DOI: 10.1586/EOG.12.34
S. Lalitkumar, P. Lalitkumar, K. Gemzell‐Danielsson
Evaluation of: White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med. 18(3), 413–421 (2012).Ovarian aging was long considered to be irrevocable in the journey of a woman´s reproductive life. But with the identification of germline stem cells, differentiating into oocytes is a landmark innovation in the field of reproductive medicine. The existing clinical and biochemical information about the ovarian reserve has been very limited. As global infertility rates are increasing, research in recent years has focused on ingenious treatments, offering promising solutions to infertile couples with ovarian failure. The article under evaluation demonstrates for the first time that candidate oogonial stem cells can be reliably isolated from adult mice and human ovaries through a FACS-based approach. This was achieved by targeting the cytoplasmic germ cell proteins Ddx4 and DDX4 in mice and humans, respecti...
[2]刘建军,刘建军,刘建军,刘建军。从育龄妇女卵巢中纯化有丝分裂活性生殖细胞形成卵母细胞。中华医学杂志,18(3),413-421(2012)。长期以来,卵巢衰老被认为是女性生殖生命旅程中不可逆转的。但随着生殖系干细胞的鉴定,分化为卵母细胞是生殖医学领域具有里程碑意义的创新。现有的关于卵巢储备的临床和生化信息非常有限。随着全球不孕症发病率的上升,近年来的研究集中在巧妙的治疗上,为卵巢功能衰竭的不孕夫妇提供了有希望的解决方案。这篇正在评估的文章首次证明了候选的卵子干细胞可以通过基于facs的方法从成年小鼠和人类卵巢中可靠地分离出来。这是通过分别靶向小鼠和人类细胞质生殖细胞蛋白Ddx4和Ddx4来实现的。
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引用次数: 1
期刊
Expert Review of Obstetrics & Gynecology
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