Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor

2000 ◽  
Vol 278 (5) ◽  
pp. C982-C988 ◽  
Author(s):  
Roni Levy ◽  
Steven D. Smith ◽  
Kala Chandler ◽  
Yoel Sadovsky ◽  
D. Michael Nelson
Keyword(s):  
Cell Differentiation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Caspase Inhibitor ◽  
Trophoblast Differentiation ◽  
Epidermal Growth ◽  
Induced Apoptosis

Preeclampsia and fetal growth restriction are associated with placental hypoperfusion and villous hypoxia. The villous response to this environment includes diminished trophoblast differentiation and enhanced apoptosis. We tested the hypothesis that hypoxia induces apoptosis in cultured trophoblasts, and that epidermal growth factor (EGF), an enhancer of trophoblast differentiation, diminishes hypoxia-induced apoptosis. Trophoblasts isolated from placentas of term-uncomplicated human pregnancies were cultured up to 72 h in standard ([Formula: see text]= 120 mmHg) or hypoxic ([Formula: see text] < 15 mmHg) conditions. Exposure to hypoxia for 24 h markedly enhanced trophoblast apoptosis as determined by DNA laddering, internucleosomal in situ DNA fragmentation, and histomorphology, as well as by the reversibility of the apoptotic process with a caspase inhibitor. Apoptosis was accompanied by increased expression of p53 and Bax and decreased expression of Bcl-2. Addition of EGF to cultured trophoblasts or exposure of more differentiated trophoblasts to hypoxia significantly lowered the level of apoptosis. We conclude that hypoxia enhances apoptosis in cultured trophoblasts by a mechanism that involves an increase in p53 and Bax expression. EGF and enhancement of cell differentiation protect against hypoxic-induced apoptosis.

scholarly journals Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1778
Author(s):  
Lewis J. Renshall ◽  
Frances Beards ◽  
Angelos Evangelinos ◽  
Susan L. Greenwood ◽  
Paul Brownbill ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Cell Turnover ◽  
Placental Dysfunction ◽  
Healthy Control ◽  
Epidermal Growth

Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.

Epidermal Growth Factor—Interactions with Normal and Malignant Urothelium: In Vivo and in Situ Studies

1987 ◽  
Vol 138 (5) ◽  
pp. 1329-1335 ◽  
Author(s):  
Edward M. Messing ◽  
Patricia Hanson ◽  
Peter Ulrich ◽  
Edrogen Erturk
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
In Situ Studies ◽  
Epidermal Growth ◽  
Factor Interactions

Increased Likelihood of Mastectomy in Human Epidermal Growth Factor Receptor 2-positive Ductal Carcinoma In Situ

2014 ◽  
Vol 80 (10) ◽  
pp. 936-939 ◽  
Author(s):  
Anna Weiss ◽  
Vivi Tran ◽  
Jennifer Baker ◽  
Hasteh Farnaz ◽  
Anne M. Wallace ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Patients with human epidermal growth factor receptor 2 (HER2neu)-positive breast invasive cancer are known to have larger, more aggressive tumors. Little research exists on the relationship between HER2neu status and extent of ductal carcinoma in situ (DCIS). A retrospective review of a single-institution database was performed for patients with DCIS between the years 2002 and 2011. A single blinded breast radiologist reviewed preoperative imaging. Pathology was reviewed for extent of DCIS. Primary outcome was mastectomy. Multivariate logistic regression was used to determine adjusted mastectomy risk. There were 166 cases, 34 HER2neu-positive. HER2neu receptor-positive patients had larger lesions on imaging: 4.0 versus 2.7 cm, by 2.9 versus 1.5 cm ( P = 0.0499 and 0.0182). HER2neu-positive patients with DCIS were more likely than HER2neu-negative to undergo mastectomy than lumpectomy (53 vs 28%, P = 0.006). Pathology revealed a trend toward larger lesions in HER2neu-positive patients (2.96 vs 2.22 cm, nonsignificant). Patients with HER2neu-positive disease were three times more likely to undergo mastectomy (odds ratio, 2.9; 95% confidence interval, 1.23 to 6.78). Patients with HER2neu-positive DCIS had greater extent of disease by imaging and were more likely to undergo mastectomy than HER2neu-negative. These findings will help surgeons counsel patients on surgical treatment.

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