References of "Gallez, Anne"
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See detailLymph/angiogenesis contributes to sex differences in lung cancer through oestrogen receptor alpha signalling
Dubois, Charline; Rocks, Natacha ULiege; Blacher, Silvia ULiege et al

in Endocrine-Related Cancer (2019), 26(2), 201-216

Oestrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of oestrogens in lung cancer development is a pre-requisite to support the development of sex-based ... [more ▼]

Oestrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of oestrogens in lung cancer development is a pre-requisite to support the development of sex-based treatments and identify patients who could potentially benefit from anti-oestrogen treatments. In this study, we highlight the contribution of lymphatic and blood endothelia in the sex-dependent modulation of lung cancer. The orthotopic graft of syngeneic lung cancer cells into immunocompetent mice showed that lung tumours grow faster in female mice than in males. Moreover, oestradiol (E2) promoted tumour development, increased lymph/angiogenesis and VEGFA and bFGF levels in lung tumours of females through an oestrogen receptor (ER) alpha-dependent pathway. Furthermore, while treatment with ERb antagonist was inefficient, ERa antagonist (MPP) and tamoxifen decreased lung tumour volumes, altered blood and lymphatic vasculature and reduced VEGFA and bFGF levels in females, but not in males. Finally, the quantification of lymphatic and blood vasculature of lung adenocarcinoma biopsies from patients aged between 35 and 55 years revealed more extensive lymphangiogenesis and angiogenesis in tumour samples issued from women than from men. In conclusion, our findings highlight an E2/ERa-dependent modulation of lymphatic and blood vascular components of lung tumour microenvironment. Our study has potential clinical implication in a personalised medicine perspective by pointing to the importance of oestrogen status or supplementation on lung cancer development that should be considered to adapt therapeutic strategies. [less ▲]

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See detailInclusion of 17β-estradiol into liposome prevent the activation of membrane initiated signaling of ERalpha
Gallez, Anne ULiege; Palazzo, Claudio; Evrard, Brigitte ULiege et al

Poster (2018)

Estrogens are implicated in many physiological and pathological processes thanks to their interaction with estrogen receptors (ERs). The estrogen receptor alpha (ERα) controls reproduction, normal mammary ... [more ▼]

Estrogens are implicated in many physiological and pathological processes thanks to their interaction with estrogen receptors (ERs). The estrogen receptor alpha (ERα) controls reproduction, normal mammary gland development and breast cancer progression. The activation of ERα by estrogens, especially by 17β-estradiol (E2), leads to two major pathways: (1) the genomic effects associated to the transcriptional activity of the ERα and (2) the MISS (Membrane Initiated Steroid Signaling) effects related to the induction of fast signaling pathways occurring when ERα is anchored to the plasma membrane. Liposome are small non-toxic and biodegradable vectors widely studied for treatment of pathologies, like multiple sclerosis, Parkinson and Alzheimer disease and cancer. The encapsulation of several types of molecules (proteins, DNA and steroids), the protection of the activity and the improvement of the pharmacokinetic properties of these compounds represent the main advantages of liposome’s use. However, the impact of the encapsulation on molecular mechanisms is not yet established. As a proof of concept, we evaluate the impact of E2 inclusion into liposome (named POPC E2) in vitro and in vivo on ERα signaling pathway activation. [less ▲]

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See detailERα- and dose-dependent effect of estetrol on angiogenesis and tumor growth
Gallez, Anne ULiege; BLACHER, Silvia ULiege; Gérard, Céline et al

Poster (2017, November 07)

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See detailWhole blood microsampling for the quantitation of estetrol without derivatization by liquid chromatography-tandem mass spectrometry
Nys, Gwenaël ULiege; Gallez, Anne ULiege; Kok, Miranda ULiege et al

in Journal of Pharmaceutical and Biomedical Analysis (2017), 140

Detailed reference viewed: 68 (36 ULiège)
See detailDose-Dependant effect of Estetrol on Angiogenesis and Tumor growth
Gallez, Anne ULiege; BLACHER, Silvia ULiege; Lenfant, Françoise et al

Conference (2017, May 19)

Detailed reference viewed: 16 (3 ULiège)
See detailDose-dependent effect of Estetrol on Angiogenesis and Tumor Growth
Gallez, Anne ULiege; Blacher, Silvia ULiege; Lenfant, Françoise et al

Poster (2017, April 24)

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and ... [more ▼]

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and they sustain the development of Estrogen Receptor α-positive tumors (ERα+). In addition, we have previously observed that estradiol (E2) can promote the growth of ERα-negative (ERα-) tumors, by increasing tumor angiogenesis that subsequently improves oxygen and nutrients delivery, thereby preventing hypoxia and necrosis. To identify new and safe drugs for the development of HRT presenting a better benefit/risk ratio, it is therefore necessary to evaluate the potential impact of new candidates on both ERα+ and ERα- tumors. In this context, estetrol (E4), a natural estrogen exclusively produced by the fetal liver, is a promising candidate. [less ▲]

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See detailAccurate Control of 17beta-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies.
Gérard, Céline ULiege; Gallez, Anne ULiege; Dubois, Charline ULiege et al

in Journal of Mammary Gland Biology and Neoplasia (2017), 22(1), 1-11

Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to ... [more ▼]

Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to-use slow releasing devices to administer steroids, especially estrogens, to small experimental animals remains the method of choice in terms of animal well-being and of safety for both the researcher and the animal. In this study, we evaluated and compared, in vitro and in vivo, the release kinetic of estradiol (E2) over sixty days from two different slow-releasing systems: the matrix pellet (MP) and the reservoir implant (RI). We compared the impact of these systems in three E2-sensitive mouse models : mammary gland development, human MCF7 adenocarcinoma xenograft and mouse melanoma progression. The real amount of E2 that is released from both types of devices could differ from manufacturer specifications due to inadequate release for MP and initial burst effect for RI. Compared to MP, the interindividual variability was reduced with RI thanks to a superior control of the E2 release. Depending on the dose-dependent sensitivity of the physiological or pathological readout studied, this could lead to an improvement of the statistical power of in vivo experiments and thus to a reduction of the required animal number. Altogether, our data draw attention on the importance to adequately select the slow-releasing device that is the most appropriated to a specific experiment to better fulfill the 3Rs rule (Replacement, Reduction, Refinement) related to animal welfare and protection. [less ▲]

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See detailEstetrol, a natural SERM exhibiting combined estrogenic and anti-estrogenic properties on mammary gland and breast cancer
Gallez, Anne ULiege; Gérard, Céline ULiege; Blacher, Silvia ULiege et al

Poster (2016, May 30)

The increased risk of breast cancer and thromboembolism in women who take hormone replacement therapy (HRT) is a major public health problem. The discovery of new drugs with better safety profile would ... [more ▼]

The increased risk of breast cancer and thromboembolism in women who take hormone replacement therapy (HRT) is a major public health problem. The discovery of new drugs with better safety profile would provide useful advances for patient care. Estetrol (E4) is a liver friendly promising candidate for HRT. In preclinical and/or clinical studies, E4 has been effective against the main symptoms of menopause from a starting dose of 0.3 mg/kg/day. The aim of this study was to define the impact of E4 on mammary gland and breast cancer development. Our preclinical data show that E4 is less efficient than estradiol (E2) to induce mammary gland growth. Treatment with several concentrations of E4 has shown that E4 did not increase tumor development, when it is used at 0.3 mg/kg/day. However, at 3 mg/kg/day, E4 increased tumor growth similarly to E2 (0.08 mg/kg/day). E4 presents also some anti-estrogenic effects on mammary gland and antitumor activity on breast cancer by decreasing the strong proliferative effect of E2. While ERα is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extra-nuclear signaling pathways are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. In conclusion, our results support that E4, if it is used in strictly controlled clinical applications, could have no or only limited impact on breast and breast cancer. [less ▲]

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See detailEtude des mécanismes d'activation des récepteurs aux oestrogènes par l'estétrol et/ou la progestérone dans le sein normal et tumoral
Gallez, Anne ULiege

Report (2016)

Estetrol (E4) is a natural estrogen we recently characterized as a Selective Estrogen Receptor Modulator (SERM) with agonistic and antagonistic activities depending on target cells. We have also evidenced ... [more ▼]

Estetrol (E4) is a natural estrogen we recently characterized as a Selective Estrogen Receptor Modulator (SERM) with agonistic and antagonistic activities depending on target cells. We have also evidenced the functional importance of mixed estrogenic/anti-estrogenic activities of E4 in normal breast development and cancer. Recent molecular studies, indicating that progesterone receptor (PGR) functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, have revolutionized our mechanistic insights of steroid receptor activities in malignant breast. E4 is a promising candidate for hormone replacement therapy (HRT) at menopause. However, the impact of the combined use of E4 and progesterone on normal breast physiology and on breast cancer development has not been evaluated yet. To fill this gap, we will evaluate the impact of treatments of E4 and/or progesterone on mammary gland development and breast cancer risk as well as on established breast cancer cells. We will unravel the molecular mechanisms driving the dual estrogenic/anti-estrogenic feature of E4 alone or combined to progesterone by evaluating the putative contribution of the extranuclear ERα, of GPER and by studying the modulation of ER/PGR interactions. This study will be conducted thanks to international collaborations (INSERM Toulouse, Reims, CNRS Rennes, Curie Institute Paris) we established through the EU SEPTIME project we coordinate. Through this project, we will bring new insights to the intriguing dual estrogenic/anti-estrogenic activity of E4. We will bring rational data about the putative safety of HRT combining E4 and progesterone. The development of an animal model assessing the effect of HRT on breast cancer risk in menopaused mice will also provide a useful tool to evaluate the effect of new HRT candidates on breast cancer risk. Moreover, the potential anti-tumor synergism of E4 and progesterone would contribute to the evolution of breast cancer treatment. [less ▲]

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See detailEstetrol, a natural SERM exhibiting combined estrogenic and antiestrogenic properties on mammary gland and breast cancer
Gérard, Céline ULiege; Gallez, Anne ULiege; Blacher, Silvia ULiege et al

Conference (2016, May 09)

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety ... [more ▼]

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety profile would provide useful advances for patient care. Estretrol (E4) appears as a promising candidate for HRT. Indeed, in contrast to current treatment containing ethinyl estradiol or estradiol (E2), E4 has a minimal impact on liver cells activity supporting a decreased incidence on thromboembolic events. In preclinical studies, E4 has been effective against the main symptoms of menopause such as hot flushes, vaginal atrophy, and osteoporosis, from a starting dose of 0.3 mg/kg/day. The aim of this study was to define the impact of E4 on mammary gland and breast cancer development when it is used at concentrations effective for menopause symptom relief. We report preclinical data showing that E4 is less efficient than E2 to induce mammary gland growth. Treatment of estrogen receptor (ER)-positive breast cancer with several concentrations of E4 has shown that 0.3 mg/kg/day E4 did not increase tumor development. However, at 3mg/kg/day, E4 increased the growth of hormone-dependent tumors and their metastatic dissemination in ovariectomized and intact mice. This effect was similar to the one observed with E2 used at 0.08 mg/kg/day. E4 presents also some anti-estrogenic effects on mammary gland and antitumor activity on breast cancer by decreasing the strong proliferative effect of E2. While ERα is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extranuclear signaling pathways are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. In conclusion, our results support that E4, if it is used in strictly controlled clinical applications, could have no or only limited impact on breast and breast cancer. [less ▲]

Detailed reference viewed: 70 (1 ULiège)
See detailImpact of estetrol on breast cancer development, metastatic dissemination and angiogenesis
Gallez, Anne ULiege; Gérard, Céline ULiege; Blacher, Silvia ULiege et al

Poster (2016)

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety ... [more ▼]

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety profile would provide useful advances for patient care. Estretrol (E4) appears as a promising candidate for HRT. Indeed, in contrast to current treatment containing ethinyl estradiol or estradiol (E2), E4 has a minimal impact on liver cells activity supporting a decreased incidence on thromboembolic events. In preclinical studies, E4 has been effective against the main symptoms of menopause such as hot flushes, vaginal atrophy, and osteoporosis, from a starting dose of 0.3 mg/kg/day. The aim of this study was to define the impact of E4 on breast cancer development when it is used at concentrations effective for menopause symptom relief. Treatment of estrogen receptor (ER)-positive breast cancer-developing mice (MMTV-PyMT) with several concentrations of E4 has shown that 0.3 mg/kg/day E4 did not increase tumor development and metastasis dissemination. However, at 3mg/kg/day, E4 increased the growth of hormone-dependent tumors and their metastatic dissemination in ovariectomized and intact mice. This effect was similar to the one observed with E2 used at 0.08 mg/kg/day. In an in vivo model of ER-negative tumors, we observed that 3mg/kg/day E4 improved tumor growth by increasing angiogenesis, and subsequently decreasing necrosis and tumor hypoxia. In contrast, 0.3 mg/kg/day E4 did not induce any of these effects on ER-negative tumors and tumor microenvironment. In conclusion, we have shown that 0.3 mg/kg/day E4, already reported to prevent menopause symptoms, does not increase breast tumor growth, metastasis dissemination, and angiogenesis. However, similarly to E2, higher concentrations of E4 are pro-tumorous. These results support that E4, if it is used in strictly controlled clinical applications, could have no or only limited impact on breast cancer. [less ▲]

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See detailQuantitative assessment of mouse mammary gland morphology using automated digital image processing and TEB detection.
Blacher, Silvia ULiege; Gérard, Céline ULiege; Gallez, Anne ULiege et al

in Endocrinology (2016)

The assessment of rodent mammary gland morphology is largely used to study the molecular mechanisms driving breast development and to analyze the impact of various endocrine disruptors with putative ... [more ▼]

The assessment of rodent mammary gland morphology is largely used to study the molecular mechanisms driving breast development and to analyze the impact of various endocrine disruptors with putative pathological implications. In this work, we propose a methodology relying on fully automated digital image analysis methods including image processing and quantification of the whole ductal tree and of the terminal end buds (TEB) as well. It allows to accurately and objectively measure both growth parameters and fine morphological glandular structures. Mammary gland elongation was characterized by two parameters: the length and the epithelial area of the ductal tree. Ductal tree fine structures were characterized by: 1) branch end-point density, 2) branching density and 3) branch length distribution. The proposed methodology was compared to quantification methods classically used in the literature. This procedure can be transposed to several software and thus largely used by scientists studying rodent mammary gland morphology. [less ▲]

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See detailEstetrol : a new natural estrogen providing a safe therapeutic window for the treatment of menopause
Gérard, Céline ULiege; Gallez, Anne ULiege; Silva, Elisabete et al

Poster (2015, November 14)

The increased risk of breast cancer and thromboembolism in women who take hormone replacement therapy (HRT) is a major public health problem. The discovery of new drugs with better safety profile would ... [more ▼]

The increased risk of breast cancer and thromboembolism in women who take hormone replacement therapy (HRT) is a major public health problem. The discovery of new drugs with better safety profile would provide useful advances for patient care. Estetrol (E4) is a liver friendly promising candidate for HRT. In preclinical and/or clinical studies, E4 has been effective against the main symptoms of menopause from a starting dose of 0.3 mg/kg/day. The aim of this study was to define the impact of E4 on mammary gland and breast cancer development. Our preclinical data show that E4 is less efficient than estradiol (E2) to induce mammary gland growth. Treatment with several concentrations of E4 has shown that E4 did not increase tumor development, when it is used at 0.3 mg/kg/day. However, at 3 mg/kg/day, E4 increased tumor growth similarly to E2 (0.08 mg/kg/day). E4 presents also some anti-estrogenic effects on mammary gland and antitumor activity on breast cancer by decreasing the strong proliferative effect of E2. While ERα is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extra-nuclear signaling pathways are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. In conclusion, our results support that E4, if it is used in strictly controlled clinical applications, could have no or only limited impact on breast and breast cancer. [less ▲]

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See detailL'estétrol et le développement tumoral
Gallez, Anne ULiege

Master's dissertation (2015)

A l’heure actuelle, le risque augmenté de troubles thromboemboliques et de cancer du sein chez les femmes sous hormonothérapie est un problème majeur de santé publique. La découverte de nouvelles ... [more ▼]

A l’heure actuelle, le risque augmenté de troubles thromboemboliques et de cancer du sein chez les femmes sous hormonothérapie est un problème majeur de santé publique. La découverte de nouvelles molécules procurant une sécurité sanitaire accrue aux utilisatrices est donc nécessaire. L’estétrol (E4) est proposé comme candidat potentiel. L’E4 est une hormone stéroïdienne, de type « œstrogène », retrouvée naturellement chez l’humain et synthétisée uniquement par le foie fœtal durant la grossesse. Sa grande biodisponibilité orale et son temps de demi-vie de 28 heures chez l’humain le rendent intéressant en tant qu’hormonothérapie de substitution (ERT/HRT). L’E4 est capable de traiter efficacement les symptômes principaux de la ménopause (les bouffées de chaleur, l’atrophie vaginale et l’ostéoporose) et ce, dès une concentration de 0,3 mg/kg/jour. L’étude de son impact sur le cancer du sein est au centre de ce mémoire, puisque c’est l’une des conséquences majeures de l’utilisation prolongée d’œstrogènes et que les données de la littérature restent controversées Des résultats préliminaires obtenus au laboratoire ont montré que l’E4 (3 mg/kg/jour) augmentait le poids des tumeurs dans le modèle murin de carcinogenèse mammaire MMTV-PyMT, contrairement à l’ovariectomie et au traitement au Tamoxifène. Au terme de ce mémoire, nos recherches démontrent que l’E4 utilisé aux doses 0,3 et 7 mg/kg/jour n’influence pas significativement la croissance tumorale. Par contre, l’E4 à 3 mg/kg/jour majore le poids tumoral et la dissémination métastatique chez des animaux ovariectomisés et intacts. De plus, l’E4 délivré à 3 mg/kg/jour est capable d’augmenter l’angiogenèse et de diminuer la nécrose et l’hypoxie intra-tumorale, de manière similaire à l’oestradiol (E2) alors que la dose de 0,3mg/kg/jour n’est pas suffisante pour observer cet effet. En conclusion, les travaux menés pendant mon mémoire de Master ont permis de caractériser les effets de l’E4 sur la carcinogenèse mammaire hormonodépendante, la dissémination métastatique et l'angiogenèse tumorale. Au vu de nos résultats, nous ne pensons pas qu'il soit judicieux d'utiliser l'E4 comme traitement anti-tumoral, comme cela a été suggéré par certains auteurs. Au contraire, nos données suggèrent que pour éviter un effet de l’E4 sur la croissance tumorale et l’angiogenèse, il est nécessaire de privilégier le développement d’un traitement clinique de la ménopause avec de faibles concentrations d’E4. [less ▲]

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