Triptorelin

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Gunter Emons - One of the best experts on this subject based on the ideXlab platform.

  • gonadotropin releasing hormone gnrh agonist Triptorelin inhibits estradiol induced serum response element sre activation and c fos expression in human endometrial ovarian and breast cancer cells
    European Journal of Endocrinology, 2004
    Co-Authors: Carsten Grundker, Andreas R Gunthert, Martin Hellriegel, Gunter Emons
    Abstract:

    BACKGROUND AND METHODS The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist Triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. RESULTS The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with Triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of Triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by Triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by Triptorelin. CONCLUSIONS The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.

  • luteinizing hormone releasing hormone induces jund dna binding and extends cell cycle in human ovarian cancer cells
    Biochemical and Biophysical Research Communications, 2002
    Co-Authors: Andreas R Gunthert, Carsten Grundker, Kirsten Hollmann, Gunter Emons
    Abstract:

    Expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors, including cancers of the ovary. This study was conducted to investigate whether LHRH induces activation of JunD and affects cell cycle regulation and DNA synthesis. Treatment of primary human ovarian cancer cells and human ovarian cancer cell lines EFO-21 and EFO-27 with LHRH agonist Triptorelin (100 nM) resulted in an increase in G(0/1) phase and a decrease in G(2/S) phase of cell cycle. Treatment of quiescent EFO-21 or EFO-27 cells with Triptorelin (100 nM) resulted in a 46.7 or 44.2-fold increase of AP-1 activation, respectively (p<0.001). Maximal binding of JunD on DNA consensus sequence was found after 4 h of treatment of quiescent EFO-21 or EFO-27 cells with Triptorelin (100 nM). DNA synthesis was significantly decreased to 45.5+/-11.4% (day 0=control=100%; p<0.001) after 3 days of Triptorelin (1 nM) treatment. These results suggest that LHRH agonist Triptorelin induces JunD-DNA binding, resulting in reduced proliferation as indicated by increased G(0/1) phase of cell cycle and decreased DNA synthesis. Since LHRH activates nucleus factor kappa B (NF kappa B) and protects ovarian cancer cells from doxorubicin-induced apoptosis and JunD is shown to decrease cell cycle and cell proliferation, we propose that JunD activated by LHRH acts as a modulator of cell proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions of LHRH.

  • expression of gonadotropin releasing hormone ii gnrh ii receptor in human endometrial and ovarian cancer cells and effects of gnrh ii on tumor cell proliferation
    The Journal of Clinical Endocrinology and Metabolism, 2002
    Co-Authors: Carsten Grundker, Andreas R Gunthert, Robert P Millar, Gunter Emons
    Abstract:

    Recently it was shown that a second GnRH system exists in primates. This study was conducted to investigate whether or not the receptor specific for GnRH type II is expressed in human endometrial and ovarian cancer cells and whether or not GnRH-II has effects on tumor cell proliferation. Expression of GnRH-II receptor mRNA in endometrial and ovarian cancer cell lines was demonstrated using RT-PCR and Southern blot analysis. The proliferation of these cell lines was dose- and time-dependently reduced by native GnRH-II. These effects were significantly more potent than the anitproliferative effects of equimolar doses of GnRH-I agonist Triptorelin (p<0.001). In the GnRH-II receptor positive but GnRH-I receptor negative ovarian cancer cell line SK-OV-3 native GnRH-II but not GnRH-I agonist Triptorelin had antiproliferative effects.

  • luteinizing hormone releasing hormone agonist Triptorelin antagonizes signal transduction and mitogenic activity of epidermal growth factor in human ovarian and endometrial cancer cell lines
    International Journal of Oncology, 1996
    Co-Authors: Gunter Emons, O Ortmann, Volker Muller, Gereon Grossmann, Ursula Trautner, Bettina V Stuckrad, Klaus Dieter Schulz, Andrew V. Schally
    Abstract:

    This study was designed to elucidate the signal transduction mechanisms, mediating the antiproliferative effects of analogs of luteinizing hormone releasing hormone (LHRH) on cell lines derived from human cancers of the ovary (EFO-21, EFO-27) and the endometrium (HEC-1A, Ishikawa). The LHRH agonist Triptorelin had no measurable effects on the activity of phospholipase C, protein kinase C, or adenylate cyclase in all 4 cell lines, though these enzymes could be activated through pharmacological stimuli. The proliferation of EFO-21, EFO-27 and HEC-1A cells in serum/phenol red-free medium was significantly stimulated by epidermal growth factor (EGF). This mitogenic effect of EGF was dose dependently antagonized by Triptorelin, without affecting the concentrations of EGF receptors. Net tyrosine phosphorylation induced by 1 nM EGF was nearly completely suppressed by simultaneous addition of 10 mu M Triptorelin or preincubation for 48 h with 100 nM Triptorelin. This inhibitory effect of the LHRH agonist on EGF-induced net tyrosine phosphorylation was partly antagonized by exposure to 100 mu M sodium vandate, an inhibitor of phosphotyrosine phosphatase. In EFO-21, EFO-27, and HEC-1A cells exposure to 100 nM EGF for 5 min induced an approximately 5-fold increase in activity of mitogen activated protein kinase (MAP-kinase)/extracellular signal regulated kinase (ERK) which was virtually nullified, when the cells were exposed for 15 min to 10 mu M Triptorelin. These data suggest that LHRH signal transduction mechanisms based on the activation of phospholipase C, protein kinase C, and adenylate cyclase, which operate in the pituitary gonadotroph, are not necessarily involved in the mediation of the antiproliferative effects of Triptorelin in these ovarian and endometrial cancer cell lines. Instead our findings support the hypothesis that Triptorelin interferes with mitogenic signal transduction, probably through antagonizing tyrosine kinase activity of the EGF receptor.

R. Kammler - One of the best experts on this subject based on the ideXlab platform.

  • neoadjuvant degarelix versus Triptorelin in premenopausal patients who receive letrozole for locally advanced endocrine responsive breast cancer a randomized phase ii trial
    Journal of Clinical Oncology, 2019
    Co-Authors: S. Dellapasqua, Kathryn P Gray, E. Munzone, D. Rubino, L. Gianni, H. Johansson, G. Viale, K. Ribi, J. Bernhard, R. Kammler
    Abstract:

    PURPOSETo evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus Triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer.PATIENTS AND METHODSPremenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2–negative breast cancer were randomly assigned to Triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to ...

  • Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial
    'American Society of Clinical Oncology (ASCO)', 2019
    Co-Authors: S. Dellapasqua, K.p. Gray, E. Munzone, D. Rubino, L. Gianni, H. Johansson, G. Viale, K. Ribi, J. Bernhard, R. Kammler
    Abstract:

    PURPOSE To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus Triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer. PATIENTS AND METHODS Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2\u2013negative breast cancer were randomly assigned to Triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level # 2.72 pg/mL [# 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided a of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms. RESULTS Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received Triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to Triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P, .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive Triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and Triptorelin plus letrozole were as expected. CONCLUSION In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with Triptorelin

Peter Humaidan - One of the best experts on this subject based on the ideXlab platform.

  • gonadotropin releasing hormone agonist trigger in oocyte donors co treated with a gonadotropin releasing hormone antagonist a dose finding study
    Fertility and Sterility, 2016
    Co-Authors: Thi Ngoc Lan Vuong, Huy Tuan Phung, Gia Bao Huynh, Peter Humaidan
    Abstract:

    Objective To determine the optimal GnRH agonist dose for triggering of oocyte maturation in oocyte donors. Design Single-center, randomized, parallel, investigator-blinded trial. Setting IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. Patient(s) One hundred sixty-five oocyte donors (aged 18–35 years, body mass index [BMI] 2 , antimullerian hormone level >1.25 ng/mL, and antral follicle count ≥6). Intervention(s) Ovulation trigger with 0.2, 0.3, or 0.4 mg Triptorelin in a GnRH antagonist cycle. Main Outcome Measure(s) The primary end point was number of metaphase II oocytes. Secondary end points were fertilization and cleavage rates, number of embryos and top-quality embryos, steroid levels, ovarian volume, and ongoing pregnancy rate (PR) in recipients. Result(s) There were no significant differences between the Triptorelin 0.2, 0.3, and 0.4 mg trigger groups with respect to number of metaphase II oocytes (16.0 ± 8.5, 15.9 ± 7.8, and 14.7 ± 8.4, respectively), embryos (13.2 ± 7.8, 11.7 ± 6.9, 11.8 ± 7.0), and number of top-quality embryos (3.8 ± 2.9, 3.6 ± 3.0, 4.1 ± 3.0). Luteinizing hormone levels at 24 hours and 36 hours after trigger was significantly higher with Triptorelin 0.4 mg versus 0.2 mg and 0.3 mg (9.8 ± 7.1 IU/L vs. 7.3 ± 4.1 IU/L and 7.2 ± 3.7 IU/L, respectively; 4.6 ± 3.2 IU/L vs. 3.2 ± 2.3 IU/L and 3.3 ± 2.1 IU/L, respectively. Progesterone level at oocyte pick-up +6 days was significantly higher in the 0.4-mg group (2.2 ± 3.7 ng/ml) versus 0.2 mg (1.1 ± 1.0 ng/ml) and 0.3 mg (1.2 ± 1.6 ng/ml). One patient developed early-onset severe ovarian hyperstimulation syndrome (OHSS). Conclusion(s) No significant differences between Triptorelin doses of 0.2, 0.3, and 0.4 mg used for ovulation trigger in oocyte donors were seen with regard to the number of mature oocytes and top-quality embryos. Clinical Trial Registration Number NCT02208986.

  • early luteal phase endocrine profile is affected by the mode of triggering final oocyte maturation and the luteal phase support used in recombinant follicle stimulating hormone gonadotropin releasing hormone antagonist in vitro fertilization cycles
    Fertility and Sterility, 2013
    Co-Authors: Human M Fatemi, Nikolaos P Polyzos, Inge Van Vaerenbergh, Claire Bourgain, Christophe Blockeel, Birgit Alsbjerg, E G Papanikolaou, Peter Humaidan
    Abstract:

    Objective To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS). Design A prospective randomized study. Setting University center for reproductive medicine. Patient(s) Four oocyte donors each underwent four consecutive cycles. Intervention(s) To avoid interpatient variation, each donor underwent the same stimulation regimen. However, different modes of triggering final oocyte maturation and LPS were administered: A) 10,000 IU hCG and standard LPS; B) GnRH agonist (GnRHa; 0.2 mg Triptorelin), and 35 hours later 1,500 IU hCG, and standard LPS; C) GnRH agonist (0.2 mg Triptorelin) and standard LPS; and D) GnRH agonist (0.2 mg Triptorelin) without LPS. Main Outcome Measure(s) Blood sampling was performed on the day of ovulation trigger, ovulation trigger + 1 day, and ovum pick-up + 5 days. Serum E 2 , FSH, LH, and P were measured. Result(s) The early luteal phase steroid levels following GnRHa trigger and modified luteal phase support (B) were similar to those seen after hCG trigger (A). However, significant differences were seen between groups A and B compared with C and D, as well as between groups C and D. Conclusion(s) Administration of a single bolus of GnRHa effectively induced LH and FSH surges in oocyte donors stimulated with recombinant FSH and cotreated with a GnRH antagonist. However, gonadotropin and steroid levels differed significantly according to the type of luteal phase support used after GnRHa trigger. European Community Clinical Trial System (EudraCT) Number 2009-009429-26.

Carsten Grundker - One of the best experts on this subject based on the ideXlab platform.

  • gonadotropin releasing hormone gnrh agonist Triptorelin inhibits estradiol induced serum response element sre activation and c fos expression in human endometrial ovarian and breast cancer cells
    European Journal of Endocrinology, 2004
    Co-Authors: Carsten Grundker, Andreas R Gunthert, Martin Hellriegel, Gunter Emons
    Abstract:

    BACKGROUND AND METHODS The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist Triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. RESULTS The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with Triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of Triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by Triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by Triptorelin. CONCLUSIONS The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.

  • luteinizing hormone releasing hormone induces jund dna binding and extends cell cycle in human ovarian cancer cells
    Biochemical and Biophysical Research Communications, 2002
    Co-Authors: Andreas R Gunthert, Carsten Grundker, Kirsten Hollmann, Gunter Emons
    Abstract:

    Expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors, including cancers of the ovary. This study was conducted to investigate whether LHRH induces activation of JunD and affects cell cycle regulation and DNA synthesis. Treatment of primary human ovarian cancer cells and human ovarian cancer cell lines EFO-21 and EFO-27 with LHRH agonist Triptorelin (100 nM) resulted in an increase in G(0/1) phase and a decrease in G(2/S) phase of cell cycle. Treatment of quiescent EFO-21 or EFO-27 cells with Triptorelin (100 nM) resulted in a 46.7 or 44.2-fold increase of AP-1 activation, respectively (p<0.001). Maximal binding of JunD on DNA consensus sequence was found after 4 h of treatment of quiescent EFO-21 or EFO-27 cells with Triptorelin (100 nM). DNA synthesis was significantly decreased to 45.5+/-11.4% (day 0=control=100%; p<0.001) after 3 days of Triptorelin (1 nM) treatment. These results suggest that LHRH agonist Triptorelin induces JunD-DNA binding, resulting in reduced proliferation as indicated by increased G(0/1) phase of cell cycle and decreased DNA synthesis. Since LHRH activates nucleus factor kappa B (NF kappa B) and protects ovarian cancer cells from doxorubicin-induced apoptosis and JunD is shown to decrease cell cycle and cell proliferation, we propose that JunD activated by LHRH acts as a modulator of cell proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions of LHRH.

  • expression of gonadotropin releasing hormone ii gnrh ii receptor in human endometrial and ovarian cancer cells and effects of gnrh ii on tumor cell proliferation
    The Journal of Clinical Endocrinology and Metabolism, 2002
    Co-Authors: Carsten Grundker, Andreas R Gunthert, Robert P Millar, Gunter Emons
    Abstract:

    Recently it was shown that a second GnRH system exists in primates. This study was conducted to investigate whether or not the receptor specific for GnRH type II is expressed in human endometrial and ovarian cancer cells and whether or not GnRH-II has effects on tumor cell proliferation. Expression of GnRH-II receptor mRNA in endometrial and ovarian cancer cell lines was demonstrated using RT-PCR and Southern blot analysis. The proliferation of these cell lines was dose- and time-dependently reduced by native GnRH-II. These effects were significantly more potent than the anitproliferative effects of equimolar doses of GnRH-I agonist Triptorelin (p<0.001). In the GnRH-II receptor positive but GnRH-I receptor negative ovarian cancer cell line SK-OV-3 native GnRH-II but not GnRH-I agonist Triptorelin had antiproliferative effects.

Kathryn P Gray - One of the best experts on this subject based on the ideXlab platform.

  • neoadjuvant degarelix versus Triptorelin in premenopausal patients who receive letrozole for locally advanced endocrine responsive breast cancer a randomized phase ii trial
    Journal of Clinical Oncology, 2019
    Co-Authors: S. Dellapasqua, Kathryn P Gray, E. Munzone, D. Rubino, L. Gianni, H. Johansson, G. Viale, K. Ribi, J. Bernhard, R. Kammler
    Abstract:

    PURPOSETo evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus Triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer.PATIENTS AND METHODSPremenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2–negative breast cancer were randomly assigned to Triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to ...

  • twelve month estrogen levels in premenopausal women with hormone receptor positive breast cancer receiving adjuvant Triptorelin plus exemestane or tamoxifen in the suppression of ovarian function trial soft the soft est substudy
    Journal of Clinical Oncology, 2016
    Co-Authors: Meritxell Bellet, Kathryn P Gray, Prudence A Francis, Istvan Lang, Eva Ciruelos, Ana Lluch, Miguel Angel Climent, Gustavo Catalan, Antoni Avella, Uriel Bohn
    Abstract:

    PurposeTo describe estradiol (E2), estrone (E1), and estrone sulfate (E1S) levels during the first year of monthly Triptorelin plus exemestane or tamoxifen and to assess possible suboptimal suppression while receiving exemestane plus Triptorelin.Patients and MethodsPremenopausal patients with early breast cancer on the Suppression of Ovarian Function Trial who selected Triptorelin as the ovarian suppression method and were randomly assigned to exemestane plus Triptorelin or tamoxifen plus Triptorelin were enrolled until the target population of 120 patients was reached. Blood sampling time points were 0, 3, 6, 12, 18, 24, 36, and 48 months. Serum estrogens were measured with a highly sensitive and specific assay. This preplanned 12-month analysis evaluated E2, E1, E1S, follicle-stimulating hormone, and luteinizing hormone levels in all patients and the proportion of patients with E2 levels greater than 2.72 pg/mL at any time point during treatment with exemestane plus Triptorelin.ResultsOne hundred sixtee...

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