scholarly journals Assessment of heparanase and heparin-binding growth and angiogenesis factors in the uterine cavity fluid in women with impaired reproduction

2014 ◽  
Vol 83 (4) ◽  
pp. 299-305
Author(s):  
Przemysław Wirstlein ◽  
Mateusz Mikołajczyk ◽  
Jana Skrzypczak

Introduction. Numerous reports lead to conclusion that either the absence or insufficient amounts of heparanase and heparin binding growth factors on the luminal surface of the epithelium in the endometrium may be associated with impaired reproduction. The aim of this study was to assess the suitability of the fluid from the uterus to predict reproductive disorders. Material and methods. The group consisted of 32 women with 2 or more consecutive unexplained miscarriages, and 33 idiopathic infertility patients; the control group comprised 22 women with normal reproductive potential. Concentration of the studied factors was assayed by ELISA in uterine fluid.Results. The uterine flushings from women with two or more consecutive miscarriages showed significantly lower concentrations of HPA1 (p < 0.001) compared to the control group and infertile patients. In contrast, we didn't observe statistically significant differences of concentration of HB-EGF, VEGF, FGF2 in the studied groups. Statistically significant correlations were obtained between the levels of HPA1 and growth factors in all groups p < 0.05. The ROC curve was used to test the diagnostic value of HPA1. With a cut-off point of 8.56 U/L for HPA1 levels, we achieved 58.6% sensitivity and 84.6% specificity in the detection of women with recurrent miscarriage compared to fertile controls and infertile women combined. The area under curve (AUC) value was 0.751. Conclusions. The procedure for determining the concentrations of HPA1, HB-EGF, VEGF, FGF2 by ELISA in fluids derived from the uterine cavity is insufficient to predict either success of reproduction or reproductive disorders.

1994 ◽  
Vol 107 (2) ◽  
pp. 401-411
Author(s):  
N. Flint ◽  
F.L. Cove ◽  
G.S. Evans

Heparin is a sulphated glycosaminoglycan derived from mast cells and has a number of functions including the inhibition of proliferation in several cell types and interactions with a range of heparin-binding growth factors. We report that heparin is a trophic factor in primary cultures of rat small intestinal epithelium. Heparin elicits a dose-dependent increase in epithelial proliferation and inhibits the growth of associated mesenchyme. The trophic effect of this molecule is not reproduced by other glycosaminoglycans including heparan sulphate but is dependent upon extensive molecular sulphation. Highly sulphated polysaccharides that are structurally unrelated to heparin (e.g. dextran sulphate and pentosan polysulphate) also stimulate epithelial proliferation in primary cultures. Heparin may act by the potentiation of mesenchyme-derived heparin-binding growth factors and these data suggest an in vivo role for mast cell-derived heparin in mucosal wound regeneration.


2002 ◽  
Vol 23 (1) ◽  
pp. 33-48 ◽  
Author(s):  
Patrick Soulié ◽  
Mélanie Héroult ◽  
Isabelle Bernard ◽  
Marie-Emmanuelle Kerros ◽  
Pierre Emmanuel Milhiet ◽  
...  

1989 ◽  
Vol 556 (1 Heparin and R) ◽  
pp. 166-172 ◽  
Author(s):  
Y. SHING ◽  
M. KLAGSBRUN ◽  
J. FOLKMAN

2000 ◽  
Vol 82 (6) ◽  
pp. 1233-1238 ◽  
Author(s):  
D G Jayne ◽  
S L Perry ◽  
E Morrison ◽  
S M Farmery ◽  
P J Guillou

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4306-4306
Author(s):  
Karène Mahtouk ◽  
Dirk Hose ◽  
Thierry Reme ◽  
John De Vos ◽  
Michel Jourdan ◽  
...  

Abstract Multiple myeloma (MM) is characterized by the accumulation of clonal malignant plasma cells in the bone marrow. One of the hallmarks of plasma cells is the expression of the heparan-sulfate proteoglycan syndecan-1. In epithelial cells, syndecan-1 plays a major role as a coreceptor for heparin-binding growth factors and chemokines. This stresses that heparin-binding growth factors may play a major role in the biology of MM cells. Recently we have demonstrated that heparin-binding EGF-like growth factor (HB-EGF), one of the ten members of the Epidermal Growth Factor (EGF) family, is produced by the tumor microenvironment and is able to trigger myeloma cell growth. As amphiregulin (AREG) is another member of the EGF family that also binds heparan-sulphate chains, we investigated its role in MM. We looked for AREG expression on a panel of 7 normal plasmablastic cells (PPCs), 7 normal bone marrow plasma cells (BMPCs), purified MM cells from 65 patients and 20 myeloma cell lines (HMCLs), with Affymetrix U133A+B microarrays. We showed that primary MM cells overexpress AREG compared to normal BMPCs and PPCs. We then investigated the expression of the ErbB receptors with real-time RT-PCR. Myeloma cells variably expressed the 4 ErbB receptors. Normal BMPCs also expressed ErbB1 and ErbB2 unlike PPCs that did not express any ErbB receptors. We demonstrated that the high AREG expression by primary myeloma cells may have a dual effect. On the one hand, AREG stimulated IL-6 production and growth of bone-marrow stromal cells that highly express the AREG ErbB1 receptor. On the other hand, AREG could promote HMCL proliferation, suggesting that a functional autocrine loop involving AREG and ErbB receptors is involved in MM cell growth. Finally, we looked for the effect of ErbB inhibitors on MM cells of 14 patients cultured for 6 days together with their bone marrow environment. A pan-ErbB inhibitor (PD-169540, Pfizer) and an ErbB1-inhibitor (IRESSA, Astrazeneca) induced strong MM cell apoptosis in respectively 71% of patients (10 of 14) and 29% of patients (4 of 14). Of major interest, when PD169540 or IRESSA were combined with dexamethasone, they induced a dramatic myeloma cell death (respectively 92% and 69% inhibition of MM cell survival), while non-myeloma cells were unaffected. Thus ErbB activation is critical to trigger MM-cell survival in short-term culture. In conclusion, our findings provide evidence for a major role of AREG and HB-EGF in the biology of multiple myeloma and identify ErbB receptors as putative therapeutic targets. These data emphasize the interest of clinical evaluation of specific-ErbB-inhibitors in patients with MM, either used alone or in combination with dexamethasone.


PRILOZI ◽  
2014 ◽  
Vol 35 (2) ◽  
pp. 95-103
Author(s):  
Gligor Tofoski ◽  
Vesna Antovska

Abstract Introduction: Patients with congenital uterine anomalies (CUA) have decreased reproductive potential and an unfavourable reproductive outcome compared to the population with normal uterine cavity. Patients with untreated CUA have a higher abortion rate, higher foetal loss rate and decreased live birth rate. Hysteroscopic metroplasty is a standard, safe and minimally invasive method for the treatment of correctible types of congenital uterine anomalies. The aim of the study was to analyse the reproductive outcome in certain groups of patients with CUA and infertility, before and after hysteroscopic metroplasty. Material and methods: We analyzed 115 patients on whom 129 hysteroscopic metroplasty interventions were performed at the University Clinic of Obstetrics and Gynaecology in Skopje over a one-year period, between 01.01.2011 and 31.12.2011. Patients and their reproductive outcome were monitored over a two-year period and the same group served as a control group, taking into account their previous reproductive history before and after metroplasty. Statistical analysis was performed using the Chi-square test and p < 0.05 was considered to be statistically significant. Results: The most common CUA were types 5b and 6, represented by 83.3%. In a follow-up period of two years, there were 55 patients with previous foetal loss treated by hysteroscopic metroplasty, and 31 of them had pregnancies. There was a statistically significant decrease of abortion rate from 88.5% to 19.3%, and a significant increase in term delivery rate from 2.3% to 71%. Conclusion: Hysteroscopic metroplasty significantly improves the reproductive outcome in patients with previous foetal loss.


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