Etienne Marbaix | UCLouvain (University of Louvain) (original) (raw)
Papers by Etienne Marbaix
The FASEB Journal, 2013
Menstrual endometrial breakdown induced by estradiol and progesterone withdrawal is regularly att... more Menstrual endometrial breakdown induced by estradiol and progesterone withdrawal is regularly attributed to vasospasm of spiral arteries causing ischemia and hypoxia. We investigated whether hypoxia actually occurred in an in vivo model of menstruation. Three complementary approaches were used to look for signs of hypoxia in fragments of human functionalis xenografted to ovariectomized immunodeficient mice bearing pellets-releasing estradiol and progesterone, and then deprived of ovarian steroids. Hormone withdrawal 21 d after grafting induced menstrual breakdown and MMP expression within 4 d. Local partial oxygen pressure (pO2) was measured by electron paramagnetic resonance using implanted lithium phtalocyanine crystals. In mice with hormone maintenance until sacrifice, pO2 was low one week after grafting (14.8±3.4 mmHg) but increased twofold from the second week when tissue was largely revascularized. After 3 wk, pO2 was not modified by hormone withdrawal but was slightly increased on hormone reimpregnation 4 d after removal (34.7±6.1 mmHg) by comparison with hormone maintenance (27.1±8.6 mmHg). These results were confirmed using fluorescence quenching-based OxyLite measurements. In a further search for signs of hypoxia, we did not find significant HIF1-α immunostaining, nor pimonidazole adducts after hormone withdrawal. We conclude that hypoxia is not needed to trigger menstrual-like tissue breakdown or repair in human endometrial xenograft.
European Respiratory Journal, 2011
Journal of Cell Science
Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early ... more Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex ster...
B-ENT
Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the ... more Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the two most widely accepted diagnostic techniques used for the assessment of parotid gland tumours. We retrospectively evaluated the ability of FNAC and MRI to predict malignancy in parotid gland tumours. Over a period of 10 years (2002-2011), parotidectomy for primary parotid gland tumours was performed in a consecutive series of 178 patients. Preoperative MRI was performed in 75% (133/178) of cases, and preoperative FNAC was performed in 70% of cases (124/178). Both modalities were applied in 53% (94/178) of patients. Sensitivity, specificity, and accuracy were analyzed retrospectively for each subgroup of patients. The sensitivity, specificity, and accuracy for predicting malignancy were 45%, 89%, and 84%, respectively, for FNAC (including only diagnostic cytology), and 40%, 88%, and 81%, respectively, for MRI. In the subgroup of patients who underwent both MRI and FNAC, sensitivity, spe...
Fertility and Sterility, 2015
To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Retrospe... more To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Retrospective histologic and immunohistochemical (IHC) study of myomas. Academic research unit. Among 59 women with symptomatic myomas who underwent myomectomy, 42 were treated preoperatively with UPA, while 17 were not. Histology and IHC were analyzed on tissue microarrays obtained from surgical specimens. Proliferation, apoptosis, extracellular matrix (ECM) remodeling, and matrix metalloproteinase 2 (MMP-2) expression. Proliferation was low in all conditions, with no statistical difference between groups. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay showed an increase in cell death in UPA-treated myomas compared with untreated myomas, but only after short-term treatment; this was not associated with elevated levels of cleaved caspase-3. After long-term treatment, cell density was higher and the ECM volume fraction lower in UPA-treated myomas than in untreated myomas. MMP-2 expression was found to be increased after treatment, showing the highest level after long-term treatment, compared with untreated myomas. Regarding sustained clinical volume reduction of myomas, this study strongly points to multifactorial mechanisms of action of UPA, involving: 1) a persistently low cell proliferation rate; 2) a limited period of cell death; and 3) ECM remodeling concomitant with stimulation of MMP-2 expression.
BMC molecular biology, 2014
YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting in the density-based switch... more YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting in the density-based switch between proliferation and differentiation. Our laboratory reported overexpression of YBX3 in clear cell renal cell arcinoma (ccRCC), as part of a wide study of YBX3 regulation in vitro and in vivo. The preliminary data was limited to 5 cases, of which only 3 could be compared to paired normal tissue, and beta-Actin was used as sole reference to normalize gene expression. We thus decided to re-evaluate YBX3 expression by real-time-PCR in a larger panel of ccRCC samples, and their paired healthy tissue, with special attention on experimental biases such as inter-individual variations, primer specificity, and reference gene for normalization. Gene expression was measured by RT-qPCR in 16 ccRCC samples, each compared to corresponding healthy tissue to minimize inter-individual variations. Eight potential housekeeping genes were evaluated for expression level and stability among the 16-paire...
B-ENT, 2014
Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal... more Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal localization is exceedingly rare. To the best of our knowledge, only four cases have been reported previously, all in Asian patients. A 61-year-old male European patient presented with hemoptysis and cough for several months. The workup revealed a primary tracheal tumor without regional or distant metastasis. The patient was treated with tracheal resection followed by end-to-end reconstruction. Pathologic analysis of the tumor, including immunohistochemistry, confirmed the diagnosis of lymphoepithelioma-like carcinoma. Testing for Epstein-Barr virus by hybridization in situ was massively positive. With a follow-up at 15 months, the patient is alive and free of disease. We report the first case of lymphoepithelioma-like carcinoma in the trachea in the European population. Treatment possibilities are discussed. They should be based on each patient's clinical presentation and the resul...
Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 2013
Hexafluorobenzene (HFB) and perfluoro-15-crown-5-ether (15C5) were compared as fluorine reporter ... more Hexafluorobenzene (HFB) and perfluoro-15-crown-5-ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using (19)F MRI for dynamic assessment of muscle oxygenation, with special focus on muscle tissue toxicity of the probes, and consecutive alteration of animal behavior. The latter were also compared in terms of sensitivity to changes in oxygenation as well as of signal-to-noise ratio for accurate pO(2) measurements. For that purpose, mouse muscles were imaged at 11.7 T, at 2- and 36-h after intramuscular injection of HFB or 15C5. Histological analysis of the muscle tissue revealed a lack of toxicity for 15C5 from 2 up to 36-h postinjection, whereas HFB induced tissue necrosis, blood clots and thrombosis as soon as 24-h postinjection. This muscle toxicity led to a limitation in mice mobility 24-h after injection of HFB as evidenced by behavioral testing (open-field, grip strength, and catwalk tests), which was not the case after 15C5 intramuscular injection. F...
Respiratory research, 2006
Inflammation plays a critical role in lung disease development and progression in cystic fibrosis... more Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the DeltaF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal cont...
Ceská gynekologie / Ceská lékarská spolecnost J. Ev. Purkyne, 2000
To investigate the regulation of perimenstrual MMP-1 expression in human endometrium. In vitro st... more To investigate the regulation of perimenstrual MMP-1 expression in human endometrium. In vitro study utilizing epithelial-stromal co-cultures. Cell Biology Unit, International Institute of Cellular and Molecular Pathology, and Departments of Pathology and Gynecology, Saint-Luc University Clinics, Louvain University Medical School, Brussels, Belgium. Contact-dependent and contact-independent co-cultures were established and resulting MMP-1 gene and protein expression was analyzed by RNase protection assays and soluble-collagen assays. MMP-1 expression in endometrial fibroblasts is markedly stimulated by epithelial cell-conditioned medium. This stimulation can be prevented by antibodies directed against interleukin 1 alpha (IL-1 alpha). Ovarian steroids inhibit MMP-1 production by IL-1 alpha-stimulated fibroblasts in vitro. Taken together, our results suggest that epithelium-derived IL-1 alpha is the most important paracrine induced of MMP-1 in endometrial fibroblasts. However, IL-1 a...
Journal of cell science, 1996
Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early ... more Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex ster...
The Biochemical journal, 1995
Human endometrial tissue, sampled at different periods of the reproductive cycle, expressed inter... more Human endometrial tissue, sampled at different periods of the reproductive cycle, expressed interstitial collagenase mRNA, protein and activity only just before and during the menstrual period. This clear-cut correlation and the inhibition of collagenase expression by progesterone and oestradiol in tissue culture point to a pivotal role of this proteinase in the mechanism of menstrual tissue breakdown and bleeding.
Cancer Microenvironment, 2008
The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects... more The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor Cancer Microenvironment (2008) 1:23-35
Cancer Immunology Research, 2014
Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resista... more Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resistance to immune rejection. In humans, constitutive expression of IDO1 has been observed in several tumor types. However, a comprehensive analysis of its expression in normal and tumor tissues is still required to anticipate the risks and potential benefits of IDO1 inhibitors. Using a newly validated monoclonal antibody to human IDO1, we performed an extensive immunohistochemical analysis of IDO1 expression in normal and tumor tissues. In normal tissues, IDO1 was expressed by endothelial cells in the placenta and lung and by epithelial cells in the female genital tract. In lymphoid tissues, IDO1 was expressed in mature dendritic cells with a phenotype (CD83(+), DC-LAMP(+), langerin(-), CD123(-), CD163(-)) distinct from plasmacytoid dendritic cells. Importantly, IDO1-expressing dendritic cells were not enriched in tumor-draining lymph nodes, in contrast with previously reported findings. IDO1-expressing cells were observed in a large fraction (505/866, 58%) of human tumors. They comprised tumor cells, endothelial cells, and stromal cells in proportions that varied depending on the tumor type. Tumors showing the highest proportions of IDO1-immunolabeled samples were carcinomas of the endometrium and cervix, followed by kidney, lung, and colon. This hierarchy of IDO1 expression was confirmed by gene expression data mined from The Cancer Genome Atlas database. Expression of IDO1 may be used to select tumors likely to benefit from targeted therapy with IDO1 inhibitors.
Background: Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in rodents. Several ... more Background: Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in rodents. Several studies have identified the capacity of CNT to stimulate the proliferation of fibroblasts. We developed and validated experimentally here a simple and rapid in vitro assay to evaluate the capacity of a nanomaterial to exert a direct pro-fibrotic effect on fibroblasts.
PLoS ONE, 2014
The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis re... more The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1b release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of profibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-b, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.
Bulletin du cancer, 2008
To evaluate the risk of finding an infiltrating endometrial carcinoma when atypical hyperplasia (... more To evaluate the risk of finding an infiltrating endometrial carcinoma when atypical hyperplasia (AH) or FIGO stage IA carcinoma were diagnosed on endometrial biopsy by Novak curette during ambulatory hysteroscopy or on pathological analysis of endometrial ablation product during operatoring hysteroscopy. Retrospective unicentric study from 2000 to 2006 including 107 patients. Total hysterectomy with bilateral oophorectomy was performed on 95 of them. All patients had initial diagnosis of AH or FIGO stage IA carcinoma realised either by biopsy with Novak curette performed according to hysteroscopic data (52 cases), or on product of endometrial ablation (43 cases). AH and stage IA carcinoma were voluntarily studied together because of the same surgical treatment and because it is acknowledged that no complementary treatment is necessary if lesion remains intramucous. However, in presence of myometrial infiltration, the risk of lymph node infiltration exists and lymphadenectomy must be...
Proceedings of The National Academy of Sciences - PNAS, 1992
Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MM... more Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MMPs). Analysis of conditioned media by zymography revealed latent and active forms of collagenase (MMP-1, EC 3.4.24.7), 72-kDa gelatinase A (MMP-2, EC 3.4.24.24), and 92-kDa gelatinase B (MMP-9, EC 3.4.24.35). These proteinases were identified by their M_r, their inhibition by tissue inhibitor of metalloproteinases, and the activation of their zymogens by trypsin or aminophenylmercuric acetate. In the absence of sex hormone, explants released large amounts of enzyme activities, as measured by densitometry of zymograms or in soluble assays. Physiological concentrations of progesterone (10-200 nM) almost totally abolished the release of collagenase, of total gelatinase activity, and of the active form of gelatinase B and largely inhibited the release of the active form of gelatinase A. These effects, which were antagonized by mifepristone (RU 38486), suggest that progesterone restrains endo...
The FASEB Journal, 2013
Menstrual endometrial breakdown induced by estradiol and progesterone withdrawal is regularly att... more Menstrual endometrial breakdown induced by estradiol and progesterone withdrawal is regularly attributed to vasospasm of spiral arteries causing ischemia and hypoxia. We investigated whether hypoxia actually occurred in an in vivo model of menstruation. Three complementary approaches were used to look for signs of hypoxia in fragments of human functionalis xenografted to ovariectomized immunodeficient mice bearing pellets-releasing estradiol and progesterone, and then deprived of ovarian steroids. Hormone withdrawal 21 d after grafting induced menstrual breakdown and MMP expression within 4 d. Local partial oxygen pressure (pO2) was measured by electron paramagnetic resonance using implanted lithium phtalocyanine crystals. In mice with hormone maintenance until sacrifice, pO2 was low one week after grafting (14.8±3.4 mmHg) but increased twofold from the second week when tissue was largely revascularized. After 3 wk, pO2 was not modified by hormone withdrawal but was slightly increased on hormone reimpregnation 4 d after removal (34.7±6.1 mmHg) by comparison with hormone maintenance (27.1±8.6 mmHg). These results were confirmed using fluorescence quenching-based OxyLite measurements. In a further search for signs of hypoxia, we did not find significant HIF1-α immunostaining, nor pimonidazole adducts after hormone withdrawal. We conclude that hypoxia is not needed to trigger menstrual-like tissue breakdown or repair in human endometrial xenograft.
European Respiratory Journal, 2011
Journal of Cell Science
Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early ... more Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex ster...
B-ENT
Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the ... more Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the two most widely accepted diagnostic techniques used for the assessment of parotid gland tumours. We retrospectively evaluated the ability of FNAC and MRI to predict malignancy in parotid gland tumours. Over a period of 10 years (2002-2011), parotidectomy for primary parotid gland tumours was performed in a consecutive series of 178 patients. Preoperative MRI was performed in 75% (133/178) of cases, and preoperative FNAC was performed in 70% of cases (124/178). Both modalities were applied in 53% (94/178) of patients. Sensitivity, specificity, and accuracy were analyzed retrospectively for each subgroup of patients. The sensitivity, specificity, and accuracy for predicting malignancy were 45%, 89%, and 84%, respectively, for FNAC (including only diagnostic cytology), and 40%, 88%, and 81%, respectively, for MRI. In the subgroup of patients who underwent both MRI and FNAC, sensitivity, spe...
Fertility and Sterility, 2015
To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Retrospe... more To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Retrospective histologic and immunohistochemical (IHC) study of myomas. Academic research unit. Among 59 women with symptomatic myomas who underwent myomectomy, 42 were treated preoperatively with UPA, while 17 were not. Histology and IHC were analyzed on tissue microarrays obtained from surgical specimens. Proliferation, apoptosis, extracellular matrix (ECM) remodeling, and matrix metalloproteinase 2 (MMP-2) expression. Proliferation was low in all conditions, with no statistical difference between groups. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay showed an increase in cell death in UPA-treated myomas compared with untreated myomas, but only after short-term treatment; this was not associated with elevated levels of cleaved caspase-3. After long-term treatment, cell density was higher and the ECM volume fraction lower in UPA-treated myomas than in untreated myomas. MMP-2 expression was found to be increased after treatment, showing the highest level after long-term treatment, compared with untreated myomas. Regarding sustained clinical volume reduction of myomas, this study strongly points to multifactorial mechanisms of action of UPA, involving: 1) a persistently low cell proliferation rate; 2) a limited period of cell death; and 3) ECM remodeling concomitant with stimulation of MMP-2 expression.
BMC molecular biology, 2014
YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting in the density-based switch... more YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting in the density-based switch between proliferation and differentiation. Our laboratory reported overexpression of YBX3 in clear cell renal cell arcinoma (ccRCC), as part of a wide study of YBX3 regulation in vitro and in vivo. The preliminary data was limited to 5 cases, of which only 3 could be compared to paired normal tissue, and beta-Actin was used as sole reference to normalize gene expression. We thus decided to re-evaluate YBX3 expression by real-time-PCR in a larger panel of ccRCC samples, and their paired healthy tissue, with special attention on experimental biases such as inter-individual variations, primer specificity, and reference gene for normalization. Gene expression was measured by RT-qPCR in 16 ccRCC samples, each compared to corresponding healthy tissue to minimize inter-individual variations. Eight potential housekeeping genes were evaluated for expression level and stability among the 16-paire...
B-ENT, 2014
Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal... more Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal localization is exceedingly rare. To the best of our knowledge, only four cases have been reported previously, all in Asian patients. A 61-year-old male European patient presented with hemoptysis and cough for several months. The workup revealed a primary tracheal tumor without regional or distant metastasis. The patient was treated with tracheal resection followed by end-to-end reconstruction. Pathologic analysis of the tumor, including immunohistochemistry, confirmed the diagnosis of lymphoepithelioma-like carcinoma. Testing for Epstein-Barr virus by hybridization in situ was massively positive. With a follow-up at 15 months, the patient is alive and free of disease. We report the first case of lymphoepithelioma-like carcinoma in the trachea in the European population. Treatment possibilities are discussed. They should be based on each patient's clinical presentation and the resul...
Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 2013
Hexafluorobenzene (HFB) and perfluoro-15-crown-5-ether (15C5) were compared as fluorine reporter ... more Hexafluorobenzene (HFB) and perfluoro-15-crown-5-ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using (19)F MRI for dynamic assessment of muscle oxygenation, with special focus on muscle tissue toxicity of the probes, and consecutive alteration of animal behavior. The latter were also compared in terms of sensitivity to changes in oxygenation as well as of signal-to-noise ratio for accurate pO(2) measurements. For that purpose, mouse muscles were imaged at 11.7 T, at 2- and 36-h after intramuscular injection of HFB or 15C5. Histological analysis of the muscle tissue revealed a lack of toxicity for 15C5 from 2 up to 36-h postinjection, whereas HFB induced tissue necrosis, blood clots and thrombosis as soon as 24-h postinjection. This muscle toxicity led to a limitation in mice mobility 24-h after injection of HFB as evidenced by behavioral testing (open-field, grip strength, and catwalk tests), which was not the case after 15C5 intramuscular injection. F...
Respiratory research, 2006
Inflammation plays a critical role in lung disease development and progression in cystic fibrosis... more Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the DeltaF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal cont...
Ceská gynekologie / Ceská lékarská spolecnost J. Ev. Purkyne, 2000
To investigate the regulation of perimenstrual MMP-1 expression in human endometrium. In vitro st... more To investigate the regulation of perimenstrual MMP-1 expression in human endometrium. In vitro study utilizing epithelial-stromal co-cultures. Cell Biology Unit, International Institute of Cellular and Molecular Pathology, and Departments of Pathology and Gynecology, Saint-Luc University Clinics, Louvain University Medical School, Brussels, Belgium. Contact-dependent and contact-independent co-cultures were established and resulting MMP-1 gene and protein expression was analyzed by RNase protection assays and soluble-collagen assays. MMP-1 expression in endometrial fibroblasts is markedly stimulated by epithelial cell-conditioned medium. This stimulation can be prevented by antibodies directed against interleukin 1 alpha (IL-1 alpha). Ovarian steroids inhibit MMP-1 production by IL-1 alpha-stimulated fibroblasts in vitro. Taken together, our results suggest that epithelium-derived IL-1 alpha is the most important paracrine induced of MMP-1 in endometrial fibroblasts. However, IL-1 a...
Journal of cell science, 1996
Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early ... more Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex ster...
The Biochemical journal, 1995
Human endometrial tissue, sampled at different periods of the reproductive cycle, expressed inter... more Human endometrial tissue, sampled at different periods of the reproductive cycle, expressed interstitial collagenase mRNA, protein and activity only just before and during the menstrual period. This clear-cut correlation and the inhibition of collagenase expression by progesterone and oestradiol in tissue culture point to a pivotal role of this proteinase in the mechanism of menstrual tissue breakdown and bleeding.
Cancer Microenvironment, 2008
The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects... more The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor Cancer Microenvironment (2008) 1:23-35
Cancer Immunology Research, 2014
Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resista... more Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resistance to immune rejection. In humans, constitutive expression of IDO1 has been observed in several tumor types. However, a comprehensive analysis of its expression in normal and tumor tissues is still required to anticipate the risks and potential benefits of IDO1 inhibitors. Using a newly validated monoclonal antibody to human IDO1, we performed an extensive immunohistochemical analysis of IDO1 expression in normal and tumor tissues. In normal tissues, IDO1 was expressed by endothelial cells in the placenta and lung and by epithelial cells in the female genital tract. In lymphoid tissues, IDO1 was expressed in mature dendritic cells with a phenotype (CD83(+), DC-LAMP(+), langerin(-), CD123(-), CD163(-)) distinct from plasmacytoid dendritic cells. Importantly, IDO1-expressing dendritic cells were not enriched in tumor-draining lymph nodes, in contrast with previously reported findings. IDO1-expressing cells were observed in a large fraction (505/866, 58%) of human tumors. They comprised tumor cells, endothelial cells, and stromal cells in proportions that varied depending on the tumor type. Tumors showing the highest proportions of IDO1-immunolabeled samples were carcinomas of the endometrium and cervix, followed by kidney, lung, and colon. This hierarchy of IDO1 expression was confirmed by gene expression data mined from The Cancer Genome Atlas database. Expression of IDO1 may be used to select tumors likely to benefit from targeted therapy with IDO1 inhibitors.
Background: Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in rodents. Several ... more Background: Carbon nanotubes (CNT) can induce lung inflammation and fibrosis in rodents. Several studies have identified the capacity of CNT to stimulate the proliferation of fibroblasts. We developed and validated experimentally here a simple and rapid in vitro assay to evaluate the capacity of a nanomaterial to exert a direct pro-fibrotic effect on fibroblasts.
PLoS ONE, 2014
The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis re... more The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1b release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of profibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-b, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.
Bulletin du cancer, 2008
To evaluate the risk of finding an infiltrating endometrial carcinoma when atypical hyperplasia (... more To evaluate the risk of finding an infiltrating endometrial carcinoma when atypical hyperplasia (AH) or FIGO stage IA carcinoma were diagnosed on endometrial biopsy by Novak curette during ambulatory hysteroscopy or on pathological analysis of endometrial ablation product during operatoring hysteroscopy. Retrospective unicentric study from 2000 to 2006 including 107 patients. Total hysterectomy with bilateral oophorectomy was performed on 95 of them. All patients had initial diagnosis of AH or FIGO stage IA carcinoma realised either by biopsy with Novak curette performed according to hysteroscopic data (52 cases), or on product of endometrial ablation (43 cases). AH and stage IA carcinoma were voluntarily studied together because of the same surgical treatment and because it is acknowledged that no complementary treatment is necessary if lesion remains intramucous. However, in presence of myometrial infiltration, the risk of lymph node infiltration exists and lymphadenectomy must be...
Proceedings of The National Academy of Sciences - PNAS, 1992
Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MM... more Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MMPs). Analysis of conditioned media by zymography revealed latent and active forms of collagenase (MMP-1, EC 3.4.24.7), 72-kDa gelatinase A (MMP-2, EC 3.4.24.24), and 92-kDa gelatinase B (MMP-9, EC 3.4.24.35). These proteinases were identified by their M_r, their inhibition by tissue inhibitor of metalloproteinases, and the activation of their zymogens by trypsin or aminophenylmercuric acetate. In the absence of sex hormone, explants released large amounts of enzyme activities, as measured by densitometry of zymograms or in soluble assays. Physiological concentrations of progesterone (10-200 nM) almost totally abolished the release of collagenase, of total gelatinase activity, and of the active form of gelatinase B and largely inhibited the release of the active form of gelatinase A. These effects, which were antagonized by mifepristone (RU 38486), suggest that progesterone restrains endo...