Biomedical subjects

J-M Foidart

Publications and source records attributed to J-M Foidart.

17 recordsLinked to original sources

PubMed2006

Regulation of vimentin by SIP1 in human epithelial breast tumor cells.

The expression of Smad interacting protein-1 (SIP1; ZEB2) and the de novo expression of vimentin are frequently involved in epithelial-to-mesenchymal transitions (EMTs) under both normal and pathological conditions. In the present study, we investigated the potential role of SIP1 in the regulation of vimentin during the EMT associated with breast tumor cell migration and invasion. Examining several breast tumor cell lines displaying various degrees of invasiveness, we found SIP1 and vimentin expression only in invasive cell lines. Also, using a model of cell migration with human mammary MCF10A cells, we showed that SIP1 is induced specifically in vimentin-positive migratory cells. Furthermore, transfection of SIP1 cDNA in MCF10A cells increased their vimentin expression both at the mRNA and protein levels and enhanced their migratory abilities in Boyden Chamber assays. Inversely, inhibition of SIP1 expression by RNAi strategies in BT-549 cells and MCF10A cells decreased vimentin expression. We also showed that SIP1 transfection did not activate the TOP-FLASH reporter system, suggesting that the beta-catenin/TCF pathway is not implicated in the regulation of vimentin by SIP1. Our results therefore implicate SIP1 in the regulation of vimentin observed in the EMT associated with breast tumor cell migration, a pathway that may contribute to the metastatic progression of breast cancer.

Base Sequence↗

PubMed2006

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC).

A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A(165) and VEGF-A(121)). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression.

ADAM Proteins↗

PubMed2005

Identification of factors important for the success of suicide gene therapy after a comparative study of Varicella zoster and Herpes simplex viral thymidine kinases efficacy on breast cancer cells.

One of the most frequently studied therapeutic strategies in the field of suicide gene therapy is based on the expression by tumor cells of the Herpes simplex virus thymidine kinase gene (HSVtk) followed by a ganciclovir (GCV) treatment. In order to investigate the potential of other enzyme/prodrug strategies, we studied in vitro and in vivo the ability of the Varicella zoster virus thymidine kinase gene (VZVtk) to act as a suicide gene and to kill non-transduced bystander cells, and compared this activity to that of its HSV counterpart. Four different antiviral compounds were tested as prodrugs. Our comparative study demonstrates the superiority of the HSVtk/GCV system among the different combinations tested and underlines the importance of both the tumor cell type and the prodrug in the success of a prodrug/suicide gene strategy.

Animals↗

PubMed2005

Automated method for the determination of a new matrix metalloproteinase inhibitor in ovine plasma and serum by coupling of restricted access material for on-line sample clean-up to liquid chromatography.

A fully automated liquid chromatographic method was developed for the determination of Ro 28-2653, a new synthetic inhibitor of matrix metalloproteinases (MMPs), in ovine serum and plasma. The method was based on the coupling of a pre-column packed with restricted access material, namely LiChrospher RP-8 ADS (alkyl diol silica), for sample clean-up to an analytical column containing octyl silica stationary phase. One hundred microl of biological sample, to which 2-propanol was automatically added, were injected onto the ADS pre-column, which was then washed with a washing liquid consisting of a mixture of 25 mM phosphate buffer (pH 7.0) and acetonitrile (90:10; v/v) for 10 min. By rotation of the switching valve, the analyte was then eluted in the back-flush mode with the LC mobile phase composed of a mixture of acetonitrile and 25 mM phosphate buffer (pH 7.0) (57:43; v/v). The UV detection was performed at 395 nm. The main parameters likely to influence the sample preparation technique were investigated. The method was then validated over a concentration range from 17.5 to 1950 ng/ml, the first concentration level corresponding to the lower limit of quantitation. At this concentration level, the mean bias and the R.S.D. value for intermediate precision were -2.4% and 4.2%, respectively.

Animals↗

PubMed2005

[Prenatal determination of fetal RHD in maternal plasma: two-years experience of routine clinical use].

OBJECTIVES: To evaluate the predictive value of RHD fetal genotype in maternal plasma of Rh D negative mothers after 10 weeks of gestation in a clinical use. MATERIAL AND METHOD: Prospective, comparative study between fetal RHD genotyping in maternal plasma, with amplification of exons 4,5,10 of the RHD gene, by real-time multiplex PCR, and Rh D serology at birth, in 218 pregnancy and their 223 babies, between November 2002 and 2004. RESULTS: Combining the amplification of three exons, the concordance rate of fetal Rh D genotyping in maternal plasma and baby phenotyping at delivery was 100%. Four women whose the babies were Rh D negative were positive for RHD exon 10 during pregnancy. This positivity was, in three cases, correlated with the presence of RHDpsi pseudogene and in last case, with a haplotype Cdes (r's). RHD genotyping was performed for five twin pregnancies. CONCLUSION: Multiplex PCR using maternal plasma provides perfect prenatal prediction of fetal RHD gene. These results confirm that this non invasive procedure is the preferred method for assessing Rh D fetal status in Rh negative mothers. Using this method for two years in routine practice has led us to modify our management scheme for sensitized Rh D-negative pregnant women.

Female↗

PubMed2005

Added benefits of drospirenone for compliance.

Drospirenone is a novel progestogen that possesses antimineralocorticoid activity. This activity is seen clinically in its effects on physiological parameters, body weight, general well-being and fluid-related symptoms. Clinical studies with an oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany) and a new continuous combined oral hormone replacement therapy (HRT) containing 1 mg 17beta-estradiol and 2 mg drospirenone (Angeliq, Schering AG) were all designed specifically to evaluate treatment effects on body weight and cardiovascular function, both of which can be influenced by aldosterone receptor antagonism. Weight gain during traditional oral contraceptive and HRT use has been one of the main reasons for poor compliance and discontinuation. Women receiving hormone therapy with 1 mg 17beta-estradiol/2 mg drospirenone had either no weight change or a small decrease, while those receiving estradiol alone tended to increase in weight. Mean body weight after 1 year of treatment with 1 mg 17beta-estradiol/2 mg drospirenone decreased by 1.2 kg (p < 0.001). Studies using different drospirenone doses in combination with estradiol indicate that the effect on body weight is dependent on the dose of drospirenone, and that this is due to drospirenone's antimineralocorticoid activity. These data are in agreement with previous studies that compared the changes in body weight in young women receiving for 13 or 26 cycles the oral contraceptives 30 microg ethinylestradiol/3 mg drospirenone or 30 microg ethinylestradiol/150 microg desogestrel (Marvelon, Organon International); 30 microg ethinylestradiol/3 mg drospirenone had a more favorable effect on body weight, with the mean body weight remaining lower than baseline for the majority of women. A variety of physical and emotional changes have been linked to hormonal fluctuations during the menstrual cycle. Fluid retention-related symptoms, such as breast tenderness, swelling, abdominal bloating and skin changes, may affect well-being and quality of life. Improvements in these cycle-dependent disorders, together with some psychological symptoms, such as fatigue and depressive mood, are well documented with the use of 30 microg ethinylestradiol/3 mg drospirenone. Therefore, the effects of hormone therapy with 1 mg 17beta-estradiol/2 mg drospirenone on quality of life were assessed in the Women's Health Questionnaire. Significant improvements were observed in quality of life during treatment with 1 mg 17beta-estradiol/2 mg drospirenone, which also resulted in higher mean scores than estradiol alone. Improvements were mainly seen in somatic symptoms, anxiety/fears and cognitive difficulties.1 mg 17beta-estradiol/2 mg drospirenone has unique antimineralocorticoid properties, which can be attributed to drospirenone. This combination prevents salt and water retention elicited by estrogens, and thereby prevents increases in blood pressure and maintains a stable body weight. Its additional beneficial impact on premenstrual symptomatology and health-related quality of life may improve well-being and clinical tolerance.

Androstenes↗

PubMed2005

[The metalloproteinases in cancer].

Tumor growth and metastatic dissemination are associated to important tissue remodelling involving matrix metalloproteinases (MMPS) acting in a concerted manner with serine proteases. Initially, it was generally accepted that proteases produced by tumor cells promote their invasive capacities by degrading extracellular matrix components. On the opposite, protease inhibitors were viewed as anti-cancer molecules. Recently, new insights into the understanding of peritumoral proteolysis were given by complete human genome sequencing and by improvement in transgenesis leading to the generation of mice deficient for genes of different proteolytic systems. Our work has evidenced the production of proteases and their inhibitors by host cells rather than by tumor cells themselves. It demonstrates the multifunctionality of proteases which can exert different effects by controlling several steps of cancer progression such as tumor growth, angiogenesis and invasion. It identifies these cells, whose genome is more stable than that of cancer cells, as potential therapeutic targets.

Animals↗

PubMed2004

Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium.

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion.

Adolescent↗

PubMed2004

Cyclodextrins as a potential carrier in drug nebulization.

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations.

Administration, Inhalation↗

PubMed2004

Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features.

Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2.

Amino Acid Sequence↗

PubMed2003

3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo.

In search for new anticancer agents, we have evaluated the antiinvasive and antimigrative properties of recently developed synthetic coumarin derivatives among which two compounds revealed important activity: 3-chlorophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate and 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate. Both drugs were able to inhibit cell invasion markedly in a Boyden chamber assay, the bromo derivative being more potent than the reference matrix metalloprotease (MMP) inhibitor GI 129471. In vivo, tumour growth was reduced when nude mice grafted with HT1080 or MDA-MB231 cells were treated i.p. 3 days week(-1) with the bromo coumarin derivative. These effects were not associated with the inhibition of urokinase, plasmin, MMP-2 or MMP-9. The mechanism of action of the drugs remains to be elucidated. However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents.

Animals↗

PubMed2003

Twin pregnancy obtained with frozen-thawed embryos after in vitro maturation in a patient with polycystic ovarian syndrome.

PURPOSE: A twin pregnancy was obtained in a patient with polycystic ovary syndrome after the transfer of three in vitro maturation-derived day 3 embryos that has been frozen and thawed. METHODS: The patient had received mild hMG stimulation followed by hCG injection. After culture for 24-48 h, mature oocytes were fertilized by ICSI. Embryos were cultured until day 3; supernumerary embryos were cryopreserved using a slow protocol. RESULTS: Among 15 nonatretic oocytes, 9 matured, 8 were fertilized. Four embryos were transferred but they did not implant. The subsequent transfer of three frozen-thawed embryos resulted in the delivery of two healthy girls. CONCLUSIONS: These results indicate that a pregnancy could be obtained with in vitro maturation-derived day-3 frozen-thawed embryos.

Adult↗

PubMed2003

Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway.

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.

Biomarkers↗

PubMed2003

[Anemia prevalence in pregnant and breast-feeding women in Lubumbashi (Democratic Republic of the Congo). Impact of malaria and intestinal helminthiasis].

OBJECTIVE: To determine the prevalence of anemia and associated factors (malaria and intestinal helminthiasis) in high risk groups of Lubumbashi, Congo, particularly in pregnant and breast-feeding women and children aged 1-2 years. MATERIAL AND METHODS: From March to May 2002, 632 pregnant women, 570 breast-feeding women, and 570 infants (1-2 years) were examined in three medical centers in Lubumbashi, Congo. Some of the subjects lived in deprived semi-urban areas (Bongonga and Sendwe), others in urban areas with a satisfactory socio-economic situation (University Clinic). RESULTS: Overall frequency of anemia was estimated between 50 and 80% in the study populations. The proportion of anemic cases was clearly higher in the Sendwe and Bongonga populations (70-80%) than in the other urban populations (50%) (P<0.01). For the three categories of examined subjects, anemia was found to be most prevalent among pregnant women (P<0.05). Anemia was found to be associated with malaria in 40% of the patients and with intestinal parasitism (ascaris / ankylostoma) in 9%. CONCLUSION: Considering these results, systematic screening and treatment of anemia and associated factors such as malaria and intestinal helminthiasis is needed for the Lubumbashi population.

Anemia↗

PubMed2002

Macrophage migration inhibitory factor (MIF) expression in human glioblastomas correlates with vascular endothelial growth factor (VEGF) expression.

Macrophage migration inhibitory factor (MIF) is a peptide released upon hypothalamo-pituitary stimulation that acts as a potent endogenous antagonist of the glucocorticoid inhibition of acute inflammatory response and subsequent antigen-specific response. MIF also sustains tumour growth as it promotes angiogenesis, overcomes p53-mediated cell growth arrest and inhibits tumour-specific immune responses. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, we studied MIF expression in 35 human glioblastomas and two normal brains. We compared these results with the expression of vascular endothelial growth factor (VEGF), the most potent angiogenic factor in glioblastomas. We detected MIF in normal cortical neurons and glial cells. All glioblastomas were positive for MIF mRNA with expression levels similar to or higher than those of normal brain. MIF immunoreactivity was seen mainly in tumour cells and less frequently in hyperplastic endothelial cells. The expressions of MIF and VEGF mRNA were strongly correlated (P < 0.0001). Our results demonstrate the expression of MIF in human glioblastomas, and indicate a close relationship with VEGF expression. This is of particular interest given the potential modulation of MIF by glucocorticosteroids.

Adult↗

PubMed2002

Human endometrial epithelial cells modulate the activation of gelatinase a by stromal cells.

Metalloproteinases (MMPs) are central effectors in endometrial physiology. Their production is tightly regulated by ovarian steroids and cytokines. Using zymography, we investigated MMP-2 production by human endometrial cells treated with estradiol-17beta + progesterone (E(2)+P) and by various key cytokines in endometrial physiology (IL-1beta, LIF, TGF-beta, and TNF-alpha). No gelatinase activity was detected in the culture media of epithelial cells. In basal conditions, stromal cells produced the pro form of MMP-2. MMP-2 production/activation was not directly affected by cytokine treatment. Interestingly, activated MMP-2 was only detected after treatment of stromal cells with culture medium from epithelial cells. Cytokine treatment of epithelial cells increased the capacity of conditioned medium to stimulate stromal cells to activate MMP-2. As the tissue inhibitor of MMP-2 (TIMP-2) is a regulator of gelatinase A activity, its concentration was measured by ELISA. TIMP-2 production by stromal cells was not affected by cytokines or by epithelial cell-conditioned medium. These results strongly suggest that regulation of stromal MMP-2 activation involves soluble factor(s) derived from the epithelial compartment.

Cytokines↗

PubMedDate not supplied

Fetal growth restriction: a workshop report.

Intrauterine growth restriction (IUGR) is associated with significantly increased perinatal morbidity and mortality as well as cardiovascular disease and glucose intolerance in adult life. A number of disorders from genetic to metabolic, vascular, coagulative, autoimmune, as well as infectious, can influence fetal growth by damaging the placenta, leading to IUGR as a result of many possible fetal, placental and maternal disorders. Strict definitions of IUGR and of its severity are needed in order to eventually distinguish among different phenotypes, such as gestational age at onset, degree of growth restriction and presence of hypoxia. This report explores and reviews some of the most recent developments in both clinical and basic research on intrauterine growth restriction, by seeking mechanisms that involve genetic factors, utero-placental nutrient availability and vascular growth factors. New exciting findings on the genomic imprinting defects potentially associated with IUGR, and the placental anomalies associated with the decreased nutrient transport are summarized. Moreover, recent data on angiogenic growth factors as well as new information arising from application of gene chip technologies are discussed.

Adult↗