The Experts below are selected from a list of 2583 Experts worldwide ranked by ideXlab platform
A O Mueck - One of the best experts on this subject based on the ideXlab platform.
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the presence of a membrane bound progesterone receptor induces growth of breast cancer with norethisterone but not with progesterone a xenograft model
Maturitas, 2017Co-Authors: Yue Zhao, H Seeger, Xiangyan Ruan, Husheng Wang, Lijuan Wang, A O MueckAbstract:Abstract Objectives During menopausal hormone therapy (MHT) a possible increase in breast cancer risk is thought to depend mainly on the progestogen component. In vitro studies have shown that the progesterone receptor membrane component 1 (PGRMC1) is important for tumor proliferation induced by Progestogens. The primary aim of this study was to compare for the first time the natural progestogen, progesterone (P), with a synthetic progestogen, norethisterone (NET), using a xenograft model. Methods MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted. After 12 days, NET or P or placebo pellets were implanted. Tumor volumes in all groups (6 mice/group) were monitored for 6–7 weeks. Immunohistochemical expression of PGRMC1 and KI-67 was assessed. These experiments were repeated using T47D cells. Results Compared with the control condition, E2 and sequential E2/NET combination increased xenograft tumor growth with MCF7 and T47D cells that transgenically expressed PGRMC1 (p Conclusions E2 plus NET increases tumor growth in human breast cancer cells overexpressing PGRMC1, but there is no change with progesterone. To our knowledge, this is the first comparison of both Progestogens in vivo using nude mice, which are frequently used in xenograft models. Clinical trials are needed to determine whether women with overexpression of PGRMC1 are at increased risk of breast cancer if NET instead of progesterone is used in MHT.
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the presence of a membrane bound progesterone receptor sensitizes the estradiol induced effect on the proliferation of human breast cancer cells
Menopause, 2011Co-Authors: H Neubauer, H Seeger, Xiangyan Ruan, Yang Yang, Tanja Fehm, Michael A Cahill, Xiaowen Tong, A O MueckAbstract:Objective Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that Progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two Progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. Methods MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and Progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). Results E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Conclusions Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of Progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.
H Seeger - One of the best experts on this subject based on the ideXlab platform.
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the presence of a membrane bound progesterone receptor induces growth of breast cancer with norethisterone but not with progesterone a xenograft model
Maturitas, 2017Co-Authors: Yue Zhao, H Seeger, Xiangyan Ruan, Husheng Wang, Lijuan Wang, A O MueckAbstract:Abstract Objectives During menopausal hormone therapy (MHT) a possible increase in breast cancer risk is thought to depend mainly on the progestogen component. In vitro studies have shown that the progesterone receptor membrane component 1 (PGRMC1) is important for tumor proliferation induced by Progestogens. The primary aim of this study was to compare for the first time the natural progestogen, progesterone (P), with a synthetic progestogen, norethisterone (NET), using a xenograft model. Methods MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted. After 12 days, NET or P or placebo pellets were implanted. Tumor volumes in all groups (6 mice/group) were monitored for 6–7 weeks. Immunohistochemical expression of PGRMC1 and KI-67 was assessed. These experiments were repeated using T47D cells. Results Compared with the control condition, E2 and sequential E2/NET combination increased xenograft tumor growth with MCF7 and T47D cells that transgenically expressed PGRMC1 (p Conclusions E2 plus NET increases tumor growth in human breast cancer cells overexpressing PGRMC1, but there is no change with progesterone. To our knowledge, this is the first comparison of both Progestogens in vivo using nude mice, which are frequently used in xenograft models. Clinical trials are needed to determine whether women with overexpression of PGRMC1 are at increased risk of breast cancer if NET instead of progesterone is used in MHT.
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the presence of a membrane bound progesterone receptor sensitizes the estradiol induced effect on the proliferation of human breast cancer cells
Menopause, 2011Co-Authors: H Neubauer, H Seeger, Xiangyan Ruan, Yang Yang, Tanja Fehm, Michael A Cahill, Xiaowen Tong, A O MueckAbstract:Objective Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that Progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two Progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. Methods MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and Progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). Results E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Conclusions Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of Progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.
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the effects of progesterone medroxyprogesterone acetate and norethisterone on growth factor and estradiol treated human cancerous and noncancerous breast cells
Menopause, 2005Co-Authors: Elizabeth A Kramer, H Seeger, Bernhard K Kramer, D Wallwiener, Alfred O MueckAbstract:OBJECTIVE: Mitogenic growth factors from stromal breast tissue and estrogens are important in growth regulation of breast cells and may modify different responses dependent on the choice of Progestogens. The effects of the acknowledged pharmacologically significantly different Progestogens, progesterone, medroxyprogesterone acetate (MPA), and norethisterone, were investigated in breast cells treated with growth factor and/or estradiol, comparing normal and primary cancer cells for the first time. DESIGN: MCF10A (human epithelial, estrogen-receptor-negative and progesterone-receptor-negative normal breast cells) were incubated with Progestogens at 1 microM and 100 nM for 7 days and epidermal growth factor, fibroblast growth factor, and insulin-like growth factor at 1 pM. HCC1500 (human estrogen-receptor-positive and progesterone-receptor-positive primary breast cancer cells) were incubated in the same way with growth factors and/or estradiol at 100 pM. Cell proliferation rate was measured by the ATP assay, whereas cell death was measured by photometric enzyme immunoassay. Ratios of cell death to proliferation were calculated from these results. RESULTS: In combination with growth factors, MPA reduced the ratio in favor of a proliferative effect in MCF10A cells, followed by norethisterone. Progesterone had no significant effect on the growth factor response. In HCC1500 cells, MPA with growth factors increased the ratio favoring inhibition, norethisterone had a proliferative effect, and progesterone had no significant effect. In combination with estradiol, MPA increased the ratio to inhibition to the greatest extent, followed by norethisterone and progesterone at 1 muM. In combination with growth factors and estradiol, MPA and norethisterone both showed an inhibitory effect, whereas progesterone had no significant effect. CONCLUSION: Certain Progestogens are able to induce the proliferation of benign or malignant human breast cells independently of the effects of growth factors and estradiol. Therefore, the choice of progestogen may be important in terms of influencing a possible breast cancer risk.
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comparison of the effect of progesterone medroxyprogesterone acetate and norethisterone on the proliferation of human breast cancer cells
The Journal of The British Menopause Society, 2003Co-Authors: H Seeger, D Wallwiener, Alfred O MueckAbstract:OBJECTIVE To investigate in vitro the influence of the three most used Progestogens in continuous combined HRT on cell proliferation of the human breast cancer cell line MCF-7. STUDY DESIGN Progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation was measured after seven days using the ATP-chemosensitivity test. RESULTS P alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and NET displayed a significant inhibition of cell proliferation between 20 and 25% for MPA and 23 and 41% for NET over the whole concentration range tested. The effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination with oestradiol, P still significantly reduced cell proliferation, the values being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was found, whereas for NET the values were between 23 and 38%. CONCLUSIONS Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women may depend on the type of progestogen used as well as on the regimen applied. However, the inhibitory in vitro net effect of the Progestogens at clinically relevant dosages is rather minimal and it remains uncertain as to whether Progestogens generally may reduce breast cancer risk in long-term treatment. Further clinical trials are urgently required to determine the appropriate choice - if any - of progestogen to complement HRT.
Xiangyan Ruan - One of the best experts on this subject based on the ideXlab platform.
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the presence of a membrane bound progesterone receptor induces growth of breast cancer with norethisterone but not with progesterone a xenograft model
Maturitas, 2017Co-Authors: Yue Zhao, H Seeger, Xiangyan Ruan, Husheng Wang, Lijuan Wang, A O MueckAbstract:Abstract Objectives During menopausal hormone therapy (MHT) a possible increase in breast cancer risk is thought to depend mainly on the progestogen component. In vitro studies have shown that the progesterone receptor membrane component 1 (PGRMC1) is important for tumor proliferation induced by Progestogens. The primary aim of this study was to compare for the first time the natural progestogen, progesterone (P), with a synthetic progestogen, norethisterone (NET), using a xenograft model. Methods MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted. After 12 days, NET or P or placebo pellets were implanted. Tumor volumes in all groups (6 mice/group) were monitored for 6–7 weeks. Immunohistochemical expression of PGRMC1 and KI-67 was assessed. These experiments were repeated using T47D cells. Results Compared with the control condition, E2 and sequential E2/NET combination increased xenograft tumor growth with MCF7 and T47D cells that transgenically expressed PGRMC1 (p Conclusions E2 plus NET increases tumor growth in human breast cancer cells overexpressing PGRMC1, but there is no change with progesterone. To our knowledge, this is the first comparison of both Progestogens in vivo using nude mice, which are frequently used in xenograft models. Clinical trials are needed to determine whether women with overexpression of PGRMC1 are at increased risk of breast cancer if NET instead of progesterone is used in MHT.
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the presence of a membrane bound progesterone receptor sensitizes the estradiol induced effect on the proliferation of human breast cancer cells
Menopause, 2011Co-Authors: H Neubauer, H Seeger, Xiangyan Ruan, Yang Yang, Tanja Fehm, Michael A Cahill, Xiaowen Tong, A O MueckAbstract:Objective Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that Progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two Progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. Methods MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and Progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). Results E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Conclusions Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of Progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.
Alfred O Mueck - One of the best experts on this subject based on the ideXlab platform.
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the effects of progesterone medroxyprogesterone acetate and norethisterone on growth factor and estradiol treated human cancerous and noncancerous breast cells
Menopause, 2005Co-Authors: Elizabeth A Kramer, H Seeger, Bernhard K Kramer, D Wallwiener, Alfred O MueckAbstract:OBJECTIVE: Mitogenic growth factors from stromal breast tissue and estrogens are important in growth regulation of breast cells and may modify different responses dependent on the choice of Progestogens. The effects of the acknowledged pharmacologically significantly different Progestogens, progesterone, medroxyprogesterone acetate (MPA), and norethisterone, were investigated in breast cells treated with growth factor and/or estradiol, comparing normal and primary cancer cells for the first time. DESIGN: MCF10A (human epithelial, estrogen-receptor-negative and progesterone-receptor-negative normal breast cells) were incubated with Progestogens at 1 microM and 100 nM for 7 days and epidermal growth factor, fibroblast growth factor, and insulin-like growth factor at 1 pM. HCC1500 (human estrogen-receptor-positive and progesterone-receptor-positive primary breast cancer cells) were incubated in the same way with growth factors and/or estradiol at 100 pM. Cell proliferation rate was measured by the ATP assay, whereas cell death was measured by photometric enzyme immunoassay. Ratios of cell death to proliferation were calculated from these results. RESULTS: In combination with growth factors, MPA reduced the ratio in favor of a proliferative effect in MCF10A cells, followed by norethisterone. Progesterone had no significant effect on the growth factor response. In HCC1500 cells, MPA with growth factors increased the ratio favoring inhibition, norethisterone had a proliferative effect, and progesterone had no significant effect. In combination with estradiol, MPA increased the ratio to inhibition to the greatest extent, followed by norethisterone and progesterone at 1 muM. In combination with growth factors and estradiol, MPA and norethisterone both showed an inhibitory effect, whereas progesterone had no significant effect. CONCLUSION: Certain Progestogens are able to induce the proliferation of benign or malignant human breast cells independently of the effects of growth factors and estradiol. Therefore, the choice of progestogen may be important in terms of influencing a possible breast cancer risk.
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comparison of the effect of progesterone medroxyprogesterone acetate and norethisterone on the proliferation of human breast cancer cells
The Journal of The British Menopause Society, 2003Co-Authors: H Seeger, D Wallwiener, Alfred O MueckAbstract:OBJECTIVE To investigate in vitro the influence of the three most used Progestogens in continuous combined HRT on cell proliferation of the human breast cancer cell line MCF-7. STUDY DESIGN Progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation was measured after seven days using the ATP-chemosensitivity test. RESULTS P alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and NET displayed a significant inhibition of cell proliferation between 20 and 25% for MPA and 23 and 41% for NET over the whole concentration range tested. The effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination with oestradiol, P still significantly reduced cell proliferation, the values being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was found, whereas for NET the values were between 23 and 38%. CONCLUSIONS Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women may depend on the type of progestogen used as well as on the regimen applied. However, the inhibitory in vitro net effect of the Progestogens at clinically relevant dosages is rather minimal and it remains uncertain as to whether Progestogens generally may reduce breast cancer risk in long-term treatment. Further clinical trials are urgently required to determine the appropriate choice - if any - of progestogen to complement HRT.
Anna M Barron - One of the best experts on this subject based on the ideXlab platform.
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protective actions of sex steroid hormones in alzheimer s disease
Frontiers in Neuroendocrinology, 2009Co-Authors: Christian J Pike, Jenna C Carroll, Emily R Rosario, Anna M BarronAbstract:Risk for Alzheimer’s disease (AD) is associated with age-related loss of sex steroid hormones in both women and men. In post-menopausal women, the precipitous depletion of estrogens and Progestogens is hypothesized to increase susceptibility to AD pathogenesis, a concept largely supported by epidemiological evidence but refuted by some clinical findings. Experimental evidence suggests that estrogens have numerous neuroprotective actions relevant to prevention of AD, in particular promotion of neuron viability and reduction of b-amyloid accumulation, a critical factor in the initiation and progression of AD. Recent findings suggest neural responsiveness to estrogen can diminish with age, reducing neuroprotective actions of estrogen and, consequently, potentially limiting the utility of hormone therapies in aged women. In addition, estrogen neuroprotective actions are also modulated by Progestogens. Specifically, continuous progestogen exposure is associated with inhibition of estrogen actions whereas cyclic delivery of Progestogens may enhance neural benefits of estrogen. In recent years, emerging literature has begun to elucidate a parallel relationship of sex steroid hormones and AD risk in men. Normal age-related testosterone loss in men is associated with increased risk to several diseases including AD. Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD-related insults, but also reduces b-amyloid accumulation. Androgen neuroprotective effects are mediated both directly by activation of androgen pathways and indirectly by aromatization to estradiol and initiation of protective estrogen signaling mechanisms. The successful use of hormone therapies in aging men and women to delay, prevent, and or treat AD will require additional research to optimize key parameters of hormone therapy and may benefit from the continuing development of selective estrogen and androgen receptor modulators.
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protective actions of sex steroid hormones in alzheimer s disease
Frontiers in Neuroendocrinology, 2009Co-Authors: Christian J Pike, Jenna C Carroll, Emily R Rosario, Anna M BarronAbstract:Risk for Alzheimer's disease (AD) is associated with age-related loss of sex steroid hormones in both women and men. In post-menopausal women, the precipitous depletion of estrogens and Progestogens is hypothesized to increase susceptibility to AD pathogenesis, a concept largely supported by epidemiological evidence but refuted by some clinical findings. Experimental evidence suggests that estrogens have numerous neuroprotective actions relevant to prevention of AD, in particular promotion of neuron viability and reduction of beta-amyloid accumulation, a critical factor in the initiation and progression of AD. Recent findings suggest neural responsiveness to estrogen can diminish with age, reducing neuroprotective actions of estrogen and, consequently, potentially limiting the utility of hormone therapies in aged women. In addition, estrogen neuroprotective actions are also modulated by Progestogens. Specifically, continuous progestogen exposure is associated with inhibition of estrogen actions whereas cyclic delivery of Progestogens may enhance neural benefits of estrogen. In recent years, emerging literature has begun to elucidate a parallel relationship of sex steroid hormones and AD risk in men. Normal age-related testosterone loss in men is associated with increased risk to several diseases including AD. Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD-related insults, but also reduces beta-amyloid accumulation. Androgen neuroprotective effects are mediated both directly by activation of androgen pathways and indirectly by aromatization to estradiol and initiation of protective estrogen signaling mechanisms. The successful use of hormone therapies in aging men and women to delay, prevent, and or treat AD will require additional research to optimize key parameters of hormone therapy and may benefit from the continuing development of selective estrogen and androgen receptor modulators.
