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【资讯翻译】Can Chemotherapy Affect Developing Ovaries in Female Fetus?

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发表于 2016-8-11 09:08:49 | 显示全部楼层 |阅读模式
Can Chemotherapy Affect Developing Ovaries in Female Fetus?Chemotherapy is considered relatively safe for the fetus when administered in the second or third trimester of pregnancy, and recent studies have yielded reassuring data. However, new findings from a study in mice suggest that chemotherapy could affect the developing ovaries in a female fetus, with adverse effects not becoming apparent until years later.


The new findings come from a study published online August 11 in BMC Cancer.


"In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb," said study author Norah Spears, DPhil, professor of reproductive physiology at the University of Edinburgh, United Kingdom, in a release.


"This study suggests that chemotherapy treatment may have important longer-term effects on the babies of women who undergo chemotherapy while pregnant, which would only become apparent in adulthood," said Dr Spears. "This is an issue that has not been explored until now."


Previous Reassuring Data Are Short Term


Cancer during pregnancy is relatively uncommon ― it is diagnosed in about 1 of every 1000 pregnancies. Depending on the cancer type and stage, chemotherapy may be recommended.


Chemotherapy administration during the first trimester is now largely avoided, owing to the risk for congenital malformations and spontaneous abortion.


However, recent studies evaluating the use of chemotherapy have found no detrimental effect on the developing fetus when it is administered after the first trimester, as previously reported by Medscape Medical News.


These studies were headed by Frederic Amant, MD, gynecologic oncologist at the University Hospitals Leuven, Belgium, and the Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands, and his group. Their findings showed that chemotherapy did not have any clear adverse effects on growth in the postnatal period, cognitive or cardiac function, or physical or mental development.


However, the follow-up from these studies is short, and long-term effects, which reach into adulthood, have not been evaluated in these patients.


The new study, although early and experimental, suggests that there may be detrimental, late effects many years after exposure.


The researchers used etoposide, which is commonly used in the treatment of ovarian and lung cancers, leukemias, and lymphomas and is considered safe for use during the second and third trimesters of pregnancy.


For their study, Dr Spears and colleagues collected fetal and neonatal ovaries from mice and cultured them in vitro with varying amounts of etoposide. However, the concentrations of etoposide used in their study were lower than those occurring in cancer patients, the researchers note.


The team reports that when the fetal ovaries were exposed to etoposide before follicle formation, damage occurred that was dependent on the dose of etoposide. The total number of follicles declined by 72% to 90% in response to medium and high doses of etoposide.


The fetal ovaries that were treated before follicular formation were damaged by 150 ng/ml etoposide, resulting in a nearly complete absence of healthy follicles.


However, for neonatal ovaries after follicle formation, exposure to etoposide was associated with only minor effects. Even at a dose of 200 ng/ml, there was no effect on the number of follicles, and the effect on follicle health was minor.


Therefore, note the authors, once the follicles have formed, the oocytes appear to be less susceptible to the deleterious effects of etoposide.


The study was supported by grants from the Medical Research Council. Dr Spears and most coauthors have disclosed no relevant financial relationships. Coauthor Nicola Powles-Glover is employed by AstraZeneca.

http://www.medscape.com/viewarticle/867318




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发表于 2016-8-11 14:29:10 | 显示全部楼层
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发表于 2016-8-11 16:28:09 | 显示全部楼层
化疗可以影响女性胎儿发育吗?

化疗被认为在妊娠中期和末期对胎儿的发育影响相对较小,最近的研究提供了可信的数据。然而,一项最新的小鼠研究表明化疗可能会影响女性胎儿卵巢的发育,这种副作用杂数年后会变得更加明显。

这项研究在线发表在8月11号的BMC cance的杂志上。

该项研究的作者来自英国英国爱丁堡大学再生生理学教授Norah Spears说: “在这项涉及到小鼠组织中的研究中,我们发现依托泊苷可以损害胎儿的卵巢发育”

Spears 说:“这项研究表明怀孕期间的妇女接受化学治疗可对胎儿造成长期的影响,而这种副作用可能在婴儿成年后变得更加显著”。他同事指出:“这项问题目前还没有被研究探索”。

之前可靠的数据并不可靠

怀孕期间发生癌症通常不易发生,大约1000个怀孕者只有一个诊断为癌症。根据不同癌症类型以及时期,化疗会被推荐使用。

在妊娠早期化疗是被禁止的,主要是由于这会提高先天性畸形和自然流产的风险。

然而,最新的研究评估了在妊娠早期后使用化学疗法对胎儿的发育没有不利的作用,正如Medscape医学新闻之前报道的一样。

这些研究是由来自鲁汶大学医院以及安东尼范列文虎克医院的妇科肿瘤专家Frederic Amant及其团队牵头的。这些发现表明化疗在产后期的生长没有明显的副作用,认知、心脏功能以及身体和心理的发育均无明显影响。

然而,这些研究的随访时间较短,而当成人后化疗的长期影响则未在这些病人当中进行评估。

这项早期和实验性的研究表明在化疗后的多年时间里,化疗可能会产生一些有害的副作用。

研究者们使用依托泊苷药物,该种药物经常被用作治疗卵巢癌、肺癌、白血病以及淋巴瘤。而且改种药物被认为是在妊娠中期和末期中使用时安全的。

在这项研究中,Spears医生及其同事收集了小鼠的胎儿和新生儿的卵巢并使用不同量的依托泊苷进行体外培养。研究者指出,在这项研究中使用的依托泊苷的浓度比在癌症病人治疗使用的量要低。


该团队报道称在卵泡形成之前将卵巢暴露在依托泊苷中,对卵巢的损害是剂量依赖性的。在培养基和不同剂量的药物下,总卵泡数量由72%下降到90%。

胎儿卵巢在卵泡形成之前已经被150 ng/ml的依托泊苷所破坏,直接导致了没有健康的卵泡的产生。

然而,对卵泡形成后的新生儿卵巢依托泊苷暴露仅仅有很小的副反应。即使在200ng/ml的浓度,对卵泡数量也无影响同时对卵巢的健康影响也较小。

因此,作者注意到一旦卵泡形成,卵母细胞更不容易受到依托泊苷的有害影响。

这项研究是由来自医学研究委员会的课题支持。Spears医生以及大多数作者宣布无相关的利益冲突。共同作者Nicola Powles-Glover是AstraZeneca的雇员。

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 楼主| 发表于 2016-8-12 16:32:14 | 显示全部楼层
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