DEVELOPING MOLECULAR THERAPEUTICS AND DIAGNOSTICS FOR PREGNANCY COMPLICATIONS

High-dose compared with low-dose oxytocin for induction of labour of nulliparous women at term

Natasha Prichard, Anthea Lindquist, Richard Hiscock, Sophie Ruff, Stephen Tong, Fiona C Brownfoot

2019-02-01

BACKGROUND: The optimal oxytocin infusion regimen to induce labour with the lowest caesarean section rate, instrumental delivery r..

EGFL7 gene expression is regulated by hypoxia in trophoblast and altered in the plasma of patients with early preeclampsia

Clare L Whitehead, Tu'uhevaha J Kaitu'u-Lino, Natalie K Binder, Sally Beard, Natasha De Alwis, Fiona Brownfoot, Stephen Tong, Natalie J Hannan

2018-10-01

INTRODUCTION: Preeclampsia is a severe complication of pregnancy, and likely arises from abnormal placental development in early p..

Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia

Natalie J Hannan, Natalie K Binder, Sally Beard, Nguyen Tuong-Vi, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong

2018-04-11

Preeclampsia is one of the most serious complications of pregnancy. Currently there are no medical treatments. Given placental oxi..

Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy

Roxanne Hastie, Elgene Lim, Pavel Sluka, Lisa Campbell, Andrew W Horne, Lenore Ellett, Natalie J Hannan, Fiona Brownfoot, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong

2018-03-01

Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that repl..

Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and decreasing endothelial dysfunction - implications for treating preeclampsia

Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Sally Beard, Ping Cannon, Roxanne Hastie, Tuong V Nguyen, Natalie K Binder, Stephen Tong, Natalie J Hannan

2018-02-21

INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors ..

Activating Transcription Factor 3 Is Reduced in Preeclamptic Placentas and Negatively Regulates sFlt-1 (Soluble fms-Like Tyrosine Kinase 1), Soluble Endoglin, and Proinflammatory Cytokines in Placenta

Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Roxanne Hastie, Ashwini Chand, Ping Cannon, Minh Deo, Laura Tuohey, Clare Whitehead, Natalie J Hannan, Stephen Tong

2017-11-01

Preeclampsia is a major pregnancy complication associated with poor placental perfusion and placental hypoxia. Systemic and placen..

Epidermal Growth Factor Rescues Endothelial Dysfunction in Primary Human Tissues In Vitro

Roxanne Hastie, Stephen Tong, Natalie J Hannan, Fiona Brownfoot, Ping Cannon, Tu'uhevaha J Kaitu'u-Lino

2017-09-01

Preeclampsia is a hypertensive disorder of pregnancy, responsible for over 60 000 maternal deaths annually. Endothelial dysfunctio..

Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction - implications as a preeclampsia treatment

Natalie J Hannan, Fiona C Brownfoot, Ping Cannon, Minh Deo, Sally Beard, Tuong V Nguyen, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2017-05-12

Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angio..

Key players of the necroptosis pathway RIPK1 and SIRT2 are altered in placenta from preeclampsia and fetal growth restriction

Natalie J Hannan, Sally Beard, Natalie K Binder, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino, Qi Chen, Laura Tuohey, Manarangi De Silva, Stephen Tong

2017-03-01

INTRODUCTION: Preeclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of perinatal morbidity and mortali..

Maternal plasma concentrations of the placental specific sFLT-1 variant, sFLT-1 e15a, in fetal growth restriction and preeclampsia

Kirsten R Palmer, Tu'uhevaha J Kaitu'u-Lino, Ping Cannon, Laura Tuohey, Manarangi S De Silva, Manuel Varas-Godoy, Stephanie Acuna, Jose Galaz, Stephen Tong, Sebastian E Illanes

2017-03-01

OBJECTIVE: sFLT-1 e15a is a recently described sFlt-1 variant that is placental and primate specific. As such, it may have potenti..

Placental-specific sFLT-1: role in pre-eclamptic pathophysiology and its translational possibilities for clinical prediction and diagnosis

KR Palmer, S Tong, TJ Kaitu'u-Lino

2017-02-01

Pre-eclampsia is a common obstetric complication globally responsible for a significant burden of maternal and perinatal morbidity..

Nuclear factor of activated T-cells (NFAT) regulates soluble fms-like tyrosine kinase-1 secretion (sFlt-1) from human placenta

Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot

2016-12-01

INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypox..

Steroid sulfatase is increased in the placentas and whole blood of women with early-onset preeclampsia

Amy M Gratton, Louie Ye, Fiona C Brownfoot, Natalie J Hannan, Clare Whitehead, Ping Cannon, Minh Deo, Peter J Fuller, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino

2016-12-01

INTRODUCTION: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies. Our team identified 137 genes highl..

ATF3 is a negative regulator of inflammation in human fetal membranes

Ratana Lim, Gillian Barker, Stella Liong, Caitlyn Nguyen-Ngo, Stephen Tong, Tu'uhevaha Kaitu'u-Lino, Martha Lappas

2016-11-01

INTRODUCTION: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9..

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening

Paul A Cohen, Nicola Flowers, Stephen Tong, Natalie Hannan, Mark D Pertile, Lisa Hui

2016-08-24

BACKGROUND: Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. P..

A comparison of sample collection methods for quantifying cell-free fetal neurodevelopment transcripts in amniotic fluid.

Lisa Hui, Stephen Tong, Tu'Uhevaha J Kaitu'u-Lino, Natalie J Hannan

2016-07-07

BACKGROUND: Cell-free RNA (cfRNA) transcripts known to be expressed by the fetal brain are detectable by quantitative reverse tran..

Effects of simvastatin, rosuvastatin and pravastatin on soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion from human umbilical vein endothelial cells, primary trophoblast cells and placenta

Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Roxanne Hastie, Ping Cannon, Tu'uhevaha J Kaitu'u-Lino

2016-05-20

BACKGROUND: Preeclampsia is associated with the placental release of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endog..

Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation

Clare L Whitehead, Helen McNamara, Susan P Walker, Maria Alexiadis, Peter J Fuller, Daniel K Vickers, Natalie J Hannan, Roxanne Hastie, Laura Tuohey, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong

2016-04-01

BACKGROUND: Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk o..

Loss of Akt increases soluble endoglin release from endothelial cells but not placenta

Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Natalie J Hannan, Fiona Brownfoot, Manarangi De Silva, Ping Cannon, Laura Tuohey, Stephen Tong

2016-04-01

INTRODUCTION: Preeclampsia is a serious pregnancy complication for which there are no medical treatments. Soluble endoglin is an a..

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction

Fiona C Brownfoot, Roxanne Hastie, Natalie J Hannan, Ping Cannon, Laura Tuohey, Laura J Parry, Sevvandi Senadheera, Sebastian E Illanes, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong

2016-03-01

BACKGROUND: Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and sol..

Placental Insufficiency in Fetuses That Slow in Growth but Are Born Appropriate for Gestational Age: A Prospective Longitudinal Study

Nadia Bardien, Clare L Whitehead, Stephen Tong, Antony Ugoni, Susan McDonald, Susan P Walker

2016-01-05

OBJECTIVES: To determine whether fetuses that slow in growth but are then born appropriate for gestational age (AGA, birthweight >..

Expectant management of severe preterm preeclampsia: a comparison of maternal and fetal indications for delivery

Samantha S Mooney, Rilka M Lee, Stephen Tong, Fiona C Brownfoot

2016-01-01

OBJECTIVE: To examine the delivery indication (maternal or fetal) for patients with preterm preeclampsia and assess whether diseas..

Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity

Kirsten R Palmer, Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Natalie J Hannan, Louie Ye, Natalie Binder, Ping Cannon, Laura Tuohey, Terrance G Johns, Alexis Shub, Stephen Tong

2015-12-01

In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal..

Heme Oxygenase-1 Is Not Decreased in Preeclamptic Placenta and Does Not Negatively Regulate Placental Soluble fms-Like Tyrosine Kinase-1 or Soluble Endoglin Secretion

Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Kenji Onda, Sally Beard, Roxanne Hastie, Natalie K Binder, Cathy Cluver, Laura Tuohey, Clare Whitehead, Fiona Brownfoot, Manarangi De Silva, Natalie J Hannan

2015-11-01

Elevated placental release of the antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG),..

A wash step at collection of placental biopsies from preeclamptic pregnancies does not adversely affect levels of sFlt-1 or endoglin

Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan, Manarangi De Silva, Natalie Binder, Laura Tuohey, Ping Cannon, Stephen Tong

2015-10-01

There is recent interest for uniform placental collection protocols so laboratories can share samples. However, concerns have been..

YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia

Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Roxanne Hastie, Ping Cannon, Laura Tuohey, Tu'uhevaha J Kaitu'u-Lino

2015-09-15

Preeclampsia is a serious complication of pregnancy with no medical treatment. It is caused by intermittent placental hypoxia and ..

Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia

Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Natalie K Binder, Susan P Walker, Ping Cannon, Roxanne Hastie, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino

2015-09-01

UNLABELLED: Preeclampsia is a major pregnancy complication where excess placental release of soluble fms-like tyrosine kinase-1 (s..

Transcription factors E2F1 and E2F3 are expressed in placenta but do not regulate MMP14

TJ Kaitu'u-Lino, R Hastie, P Cannon, H Nguyen, S Lee, NJ Hannan, S Tong

2015-08-01

INTRODUCTION: Preeclampsia is a serious complication of pregnancy for which there are no efficacious medical treatments. Soluble e..

Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation

Owen Stock, Lavinia Gordon, Jada Kapoor, Susan P Walker, Clare Whitehead, Tu'uhevaha J Kaitu'u-Lino, Gabrielle Pell, Natalie J Hannan, Stephen Tong

2015-07-01

BACKGROUND: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of..

Paternal obesity in a rodent model affects placental gene expression in a sex-specific manner

Natalie K Binder, Sally A Beard, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Natalie J Hannan, David K Gardner

2015-05-01

Fetal growth restriction (FGR) is a major obstetric complication stemming from poor placental development. We have previously demo..

Sofalcone Upregulates the Nuclear Factor (Erythroid-Derived 2)-Like 2/Heme Oxygenase-1 Pathway, Reduces Soluble fms-Like Tyrosine Kinase-1, and Quenches Endothelial Dysfunction Potential Therapeutic for Preeclampsia

Kenji Onda, Stephen Tong, Anzu Nakahara, Mei Kondo, Hideaki Monchusho, Toshihiko Hirano, Tu'uhevaha Kaitu'u-Lino, Sally Beard, Natalie Binder, Laura Tuohey, Fiona Brownfoot, Natalie J Hannan

2015-04-01

Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfun..

Molecular diagnostics and therapeutics for ectopic pregnancy

Stephen Tong, Monika M Skubisz, Andrew W Horne

2015-02-01

Ectopic pregnancies are a serious gynaecological emergency that can be fatal. As such, prompt diagnosis and safe timely treatment ..

Placental SEMA3B expression is not altered in severe early onset preeclampsia

TJ Kaitu'u-Lino, R Hastie, P Cannon, NK Binder, S Lee, O Stock, NJ Hannan, S Tong

2014-12-01

Recent evidence suggests that Semaphorin 3B (SEMA3B) is upregulated in severe preeclampsia, and a major driver of cytotrophoblast ..

Stability of absolute copy number of housekeeping genes in preeclamptic and normal placentas, as measured by digital PCR

TJ Kaitu'u-Lino, R Hastie, P Cannon, S Lee, O Stock, NJ Hannan, R Hiscock, S Tong

2014-12-01

Measuring mRNA expression is fundamental to placental research. Ideally, mRNA transcript numbers are directly quantified. However,..

Characterization of protocols for primary trophoblast purification, optimized for functional investigation of sFlt-1 and soluble endoglin

Tu'uhevaha J Kaitu'u-Lino, Stephen Tong, Sally Beard, Roxanne Hastie, Laura Tuohey, Fiona Brownfoot, Kenji Onda, Natalie J Hannan

2014-10-01

OBJECTIVES: Soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) are the most studied molecules in preeclampsia..

Peptides do not prevent cleavage of endoglin to produce soluble endoglin

Roxanne Hastie, Stephen Tong, Ping Cannon, Fiona Brownfoot, Natalie J Hannan, Tu'uhevaha Kaitu'u-Lino

2014-10-01

MMP14 cleaves membrane bound endoglin to produce soluble endoglin (sEng), an anti-angiogenic factor that causes endothelial dysfun..

Soluble endoglin production is upregulated by oxysterols but not quenched by pravastatin in primary placental and endothelial cells

FC Brownfoot, N Hannan, K Onda, S Tong, T Kaitu'u-Lino

2014-09-01

INTRODUCTION: Preeclampsia is a serious pregnancy complication. Soluble endoglin (sEng) is released from the placenta and contribu..

Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series

AW Horne, MM Skubisz, S Tong, WC Duncan, P Neil, EM Wallace, TG Johns

2014-07-01

Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortali..

Measuring hypoxia-induced RNA in maternal blood: a new way to identify critically hypoxic fetuses in utero?

Clare L Whitehead, Stephen Tong

2014-06-01

Severe fetal hypoxia causes stillbirth and permanent childhood disability. Unfortunately, none of the current tests is precise at ..

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Natalie J Hannan, Katerina Bambang, Tu'uhevaha J Kaitu'u-Lino, Justin C Konje, Stephen Tong

2014-04-03

BACKGROUND: We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 ..

Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage

EM Menkhorst, T Gamage, C Cuman, TJ Kaitu'u-Lino, S Tong, E Dimitriadis

2014-03-01

INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implanta..

Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in utero fetal hypoxic status

Clare Whitehead, Wan Tinn Teh, Susan P Walker, Cheryl Leung, Sonali Mendis, Luke Larmour, Stephen Tong

2013-12-08

BACKGROUND: Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses..

Combination Gefitinib and Methotrexate Compared With Methotrexate Alone to Treat Ectopic Pregnancy

Monika M Skubisz, Andrew W Horne, Terrance G Johns, Ulrika W Nilsson, W Colin Duncan, Euan M Wallace, Hilary OD Critchley, Stephen Tong

2013-10-01

OBJECTIVE: To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnanc..

Effects of Gefitinib, an Epidermal Growth Factor Receptor Inhibitor, on Human Placental Cell Growth

Ulrika W Nilsson, Terrance G Johns, Tania Wilmann, Tu'uhevaha Kaitu'u-Lino, Clare Whitehead, Eva Dimitriadis, Ellen Menkhorst, Burcu Saglam, Yane Gao, Sameer A Greenall, Andrew W Horne, Stephen Tong

2013-10-01

OBJECTIVE: Placenta has the highest expression of epidermal growth factor (EGF) receptor of all tissues, a cell signaling pathway ..

Plasma MIC-1 and PAPP-A Levels Are Decreased among Women Presenting to an Early Pregnancy Assessment Unit, Have Fetal Viability Confirmed but Later Miscarry

Tu'uhevaha J Kaitu'u-Lino, Katerina Bambang, Joseph Onwude, Richard Hiscock, Justin Konje, Stephen Tong

2013-09-12

BACKGROUND: We have recently shown first trimester Macrophage inhibitory cytokine-1 (MIC-1) and Pregnancy Associated Plasma Protei..

Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study

Mathis Grossmann, Rudolf Hoermann, Claire Francis, Emma J Hamilton, Aye Tint, Tu'uhevaha Kaitu'u-Lino, Kent Kuswanto, Martha Lappas, Ken Sikaris, Jeffery D Zajac, Michael Permezel, Stephen Tong

2013-05-14

BACKGROUND: There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the ris..