84 research outputs found
Nutri-epigenetics and gut microbiota: How birth care, bonding and breastfeeding can influence and be influenced?
Maternal lifestyle is an important factor in the programming of an infantâs epigenome, in particular when considered alongside the mode of birth and choice of feeding method (i.e., breastfeeding or formula feeding). Beginning in utero, and during the first two years of an infantâs life, cells acquire an epigenetic memory of the neonatal exposome which can be influential across the entire lifespan. Parental lifestyle (e.g., malnutrition, alcohol intake, smoke, stress, exposure to xenobiotics and/or drugs) can modify both the maternal and paternal epigenome, leading to epigenetic inheritance in their offspring. This review aims to outline the origin of early life modulation of the epigenome, and to share this fundamental concept with all the health care professionals involved in the development and provision of care during childbirth in order to inform future parents and clinicians of the importance of the this process and the key role it plays in the programming of a childâs health
Soluble Flt-1 and PlGF: new markers of early pregnancy loss?
Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (nâ=â40), from asymptomatic controls (nâ=â32) and from non- pregnant women in their luteal phase (nâ=â14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P10 fold) and MS PlGF (âŒ2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (âŒ25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss
The relevance of reducing Veress needle overshooting
Safe insertion of the Veress needle during laparoscopy relies on the surgeonsâ technical skills in order
to stop needle insertion just in time to prevent overshooting in the underlying organs. To reduce this
risk, a wide variety of Veress needle systems were developed with safety mechanisms that limit the
insertion speed, insertion depth or decouple the driving force generated by the surgeonâs hand on
the needle. The aim of this study is to evaluate current surgeonsâ perceptions related to the use of
Veress needles and to investigate the relevance of preventing overshooting of Veress needles among
members of the European Association of Endoscopic Surgery (EAES). An online survey was distributed
by the EAES Executive Office to all active members. The survey consisted of demographic data and
14 questions regarding the use of the Veress needle, the training conducted prior to usage, and the
need for any improvement. A total of 365 members residing in 58 different countries responded the
survey. Of the responding surgeons, 36% prefer the open method for patients with normal body mass
index (BMI), and 22% for patients with high BMI. Of the surgeons using Veress needle, 68% indicated
that the reduction of overshoot is beneficial in normal BMI patients, whereas 78% indicated that this
is beneficial in high BMI patients. On average, the members using the Veress needle had used it for
1448 (SD 3031) times and felt comfortable on using it after 22,9 (SD 78,9) times. The average years
of experience was 17,6 (SD 11,1) and the surgeons think that a maximum overshoot of 9.4 (SD 5.5)
mm is acceptable before they can safely use the Veress needle. This survey indicates that despite the
risks, Veress needles are still being used by the majority of the laparoscopic surgeons who responded.
In addition, the surgeons responded that they were interested in using a Veress needle with an extra
safety mechanism if it limits the risk of overshooting into the underlying structures.peer-reviewe
Epithelioid trophoblastic tumour : a case with genetic linkage to a child born over seventeen years prior, successfully treated with surgery and pembrolizumab
Epithelioid trophoblastic tumours are rare neoplasms showing differentiation towards the chorion leave-type intermediate cytotrophoblast, with only a handful of cases being reported in the literature. These tumours are slow-growing and are typically confined to the uterus for extended periods of time. While the pathogenesis is unclear, they are thought to arise from a remnant intermediate trophoblast originating from prior normal pregnancies or, less frequently, gestational trophoblastic tumours. A protracted time period between the gestational event and tumour development is typical. This case describes a 49-year-old previously healthy female who presented with a completely asymptomatic uterine mass, discovered incidentally during a routine gynaecological assessment. The pathological analysis of the hysterectomy specimen confirmed an epithelioid trophoblastic tumour, involving the uterus and cervix. This is a rare gynaecological tumour. A comparative short tandem repeat analysis revealed genetic similarities to a previous healthy gestation seventeen years prior. She was successful treated with adjuvant pembrolizumab, with no evidence of disease recurrence to date.peer-reviewe
Could MicroRNAs be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview
Gynecological cancers pose an important public health issue, with a high incidence among
women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal
tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma
and melanoma of the female genital tract, are defined as rare with an annual incidence of
<6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and
given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience
and limited therapeutic options. There has been a growing interest in the field of microRNAs
(miRNAs), a class of small non-coding RNAs of 22 nucleotides in length, because of their potential
to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational
repression by interacting with the 30 untranslated region (30-UTR) of target mRNAs, as well as
other regions and gene promoters, as well as activating translation or regulating transcription under
certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the
diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few
studies have been performed on RGCs. In this review, we summarize the data currently available
regarding RGCs.peer-reviewe
An overview of the role of long non-coding RNAs in human choriocarcinoma
Funding: The publication of this manuscript was funded by the European Cooperation in Science & Technology Program (EU COST)âCOST Action CA18117: GYNOCARE- âEuropean network for Gynaecological Rare Cancer research: From Concept to Cureâ. R.D.F., S.S., A.F., S.A.O., J.J.O., M.P.W., J.B., M.S., P.O., A.Y., M.V.-S., B.E., A.G., and J.C.-A. are Action management committee members and/or form part of Working Groups 1â3, and J.C.-A. is the Chairperson of this Action.Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.publishersversionpublishe
GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic TumorsâCurrent Challenges and Future Directions
More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of â€6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on expert opinion, retrospective studies, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges through the creation of a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, âBasic and Translational Research on Rare Gynecological Cancerâ) have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state-of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide
Serum Concentrations of Soluble Flt-1 Are Decreased among Women with a Viable Fetus and No Symptoms of Miscarriage Destined for Pregnancy Loss
Miscarriage is the most common complication of pregnancy. Pre-clinical miscarriage has an estimated incidence of 30%, whilst clinical miscarriage has an incidence of 12-15%. Two thirds of pregnancies lost to miscarriage are believed to be attributable to defective placentation, thus a number of studies have sought to identify markers of defective placentation that could be used as clinical biomarkers of miscarriage. Decreased soluble FMS-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) in the maternal circulation during the first trimester have recently been proposed as potential markers of pregnancy loss. However, in these studies clinical samples were only obtained once women had presented with symptoms of miscarriage. In this study we prospectively screened serum samples collected from asymptomatic women with a viable fetus. We assessed maternal serum levels of sFlt1, PlGF and sEng across the first trimester of normal pregnancy and compared levels between women who continued to a live birth, to those who subsequently miscarried. Both sFlt1 and PlGF significantly (pâ€0.05) increased across gestation in normal pregnancy with serum levels rising from 0.65±0.12 ng/ml at 6 weeks to 1.85±0.24 ng/ml at 12 weeks for sFlt1, and 57.2±19.2 pg/ml to 106±22.7 pg/ml for PlGF. sEng remained unchanged throughout the the first trimester. Importantly we detected a significant (35%, pâ€0.05) decrease in sFlt1 levels between our control and miscarriage cohort, however there was significant overlap between cases and controls, suggesting serum sFlt1 is unlikely to be useful as a clinical biomarker in asymptomatic women. Nevertheless, our data suggests a dysregulation of angiogenic factors may be involved in the pathophysiology of miscarriage
GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic TumorsâCurrent Challenges and Future Directions
More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of â€6 per 100, 000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on retrospective studies, expert opinion, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges by creating a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, âBasic and Translational Research on Rare Gynecological Cancerâ) have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide
LncRNA MORT (ZNF667-AS1) in cancer â is there a possible role in gynecological malignancies?
Gynecological cancers (GCs) are currently among the major threats to female health.
Moreover, there are different histologic subtypes of these cancers, which are defined as ârareâ due to
an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a
poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development
of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes
or oncogenes, depending on their function within the cellular context and the signaling pathways
in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due
to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the
mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in
humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT;
alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the
human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in
several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent
studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer.
Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker
and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).peer-reviewe
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