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Sample records for hormone receptor-positive early

  1. Practical consensus recommendations regarding the management of hormone receptor positive early breast cancer in elderly women

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    Govind Babu

    2018-01-01

    Full Text Available Breast cancer is a leading cause of death among women, and its incidence increases with age. Currently the treatment of breast cancer in older patients is almost identical to their younger counterparts. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations for the benefit of community oncologists regarding the management of early breast cancer specifically in elderly women.

  2. Surgery Should Complement Endocrine Therapy for Elderly Postmenopausal Women with Hormone Receptor-Positive Early-Stage Breast Cancer

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    Olivier Nguyen

    2012-01-01

    Full Text Available Introduction. Endocrine therapy (ET is an integral part of breast cancer (BC treatment with surgical resection remaining the cornerstone of curative treatment. The objective of this study is to compare the survival of elderly postmenopausal women with hormone receptor-positive early-stage BC treated with ET alone, without radiation or chemotherapy, versus ET plus surgery. Materials and Methods. This is a retrospective study based on a prospective database. The medical records of postmenopausal BC patients referred to the surgical oncology service of two hospitals during an 8-year period were reviewed. All patients were to receive ET for a minimum of four months before undergoing any surgery. Results. Fifty-one patients were included and divided in two groups, ET alone and ET plus surgery. At last follow-up in exclusive ET patients (n=28, 39% had stable disease or complete response, 22% had progressive disease, of which 18% died of breast cancer, and 39% died of other causes. In surgical patients (n=23, 78% were disease-free, 9% died of recurrent breast cancer, and 13% died of other causes. Conclusions. These results suggest that surgical resection is beneficial in this group and should be considered, even for patients previously deemed ineligible for surgery.

  3. Chemotherapy-induced amenorrhea and the resumption of menstruation in premenopausal women with hormone receptor-positive early breast cancer.

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    Koga, Chinami; Akiyoshi, Sayuri; Ishida, Mayumi; Nakamura, Yoshiaki; Ohno, Shinji; Tokunaga, Eriko

    2017-09-01

    For premenopausal women with breast cancer, information on the effects of chemotherapy and the risk of infertility is important. In this study, the effect of chemotherapy on the ovarian function in premenopausal women with hormone receptor-positive breast cancer was investigated, with an age-stratified analysis of the appearance of amenorrhea and the resumption of menstruation after the use of chemotherapy with anthracyclines or taxanes. Premenopausal women diagnosed with operable Stage I-III hormone receptor-positive breast cancer and underwent neoadjuvant or adjuvant chemotherapy with the standard regimen of anthracyclines and/or taxanes were included. The patients were classified into age groups in 5-year increments, and the rates of chemotherapy-induced amenorrhea (CIA), resumption of menstruation, and duration of CIA after chemotherapy were analyzed. The subjects consisted of 101 patients (median age 45 years). CIA occurred in 97 (96%) patients and 40 patients resumed menstruation. In all patients aged ≤39 years menstruation restarted, whereas in all patients aged ≥50 years, menstruation did not restart. For the patients who resumed menstruation, the younger the patients, the sooner menstruation tended to restart. The resumption of menstruation occurred within 1 year for younger patients aged around 30 years, but for those aged ≥35 years, 60% of cases took around 2-3 years for resumption. The incidence of CIA, the resumption of menstruation and duration of CIA after chemotherapy depend greatly on the patient's age.

  4. Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer.

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    Schramm, Amelie; Schochter, Fabienne; Friedl, Thomas W P; de Gregorio, Nikolaus; Andergassen, Ulrich; Alunni-Fabbroni, Marianna; Trapp, Elisabeth; Jaeger, Bernadette; Heinrich, Georg; Camara, Oumar; Decker, Thomas; Ober, Angelika; Mahner, Sven; Fehm, Tanja N; Pantel, Klaus; Fasching, Peter A; Schneeweiss, Andreas; Janni, Wolfgang; Rack, Brigitte K

    2017-07-01

    Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary

  5. Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

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    Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

    2016-12-27

    This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

  6. Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

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    Wilson, Sheridan; Speers, Caroline; Tyldesley, Scott; Chia, Stephen; Kennecke, Hagen; Ellard, Susan; Lohrisch, Caroline

    2016-08-01

    Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial.

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    Yang, H; Zong, X; Yu, Y; Shao, G; Zhang, L; Qian, C; Bian, Y; Xu, X; Sun, W; Meng, X; Ding, X; Chen, D; Zou, D; Xie, S; Zheng, Y; Zhang, J; He, X; Sun, C; Yu, X; Ni, J

    2013-08-06

    This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer. This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months. Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (Pwomen in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups. The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.

  8. [Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

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    Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

    2018-01-01

    If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  9. Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

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    Mori, Ryutaro; Nagao, Yasuko

    2014-01-01

    According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

  10. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials.

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    Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Fleming, Gini F; Walley, Barbara A; Kammler, Roswitha; Dell'Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N; Coates, Alan S; Gelber, Richard D; Viale, Giuseppe

    2015-11-01

    The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer.

  11. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

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    Yardley DA

    2016-05-01

    Full Text Available Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. Keywords: breast cancer, bone metastases, hormone receptor-positive, bone-related complications, interventions, management and management strategies, estrogen receptor-positive

  12. Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer.

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    Robinson, Penelope J; Bell, Robin J; Davis, Susan R

    2014-11-01

    Whether moderate to severe obesity (body mass index (BMI)≥30 to women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (women, mean age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, pobesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event. Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Efficacy of palbociclib plus fulvestrant after everolimus in hormone receptor-positive metastatic breast cancer.

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    du Rusquec, Pauline; Palpacuer, Clément; Campion, Loic; Patsouris, Anne; Augereau, Paule; Gourmelon, Carole; Robert, Marie; Dumas, Laurence; Caroline, Folliard; Campone, Mario; Frenel, Jean-Sébastien

    2018-04-01

    Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population. From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed. 60 patients were treated accordingly; median age was 61 years; 50 patients (83.3%) had visceral metastasis, and 10 (16.7%) had bone-only disease. Patients had previously received a median of 5 (1-14) lines of treatment, including ET (median 3) and chemotherapy (median 2); 28 (46.7%) received previously fulvestrant and all everolimus. With a median follow-up of 10.3 months, median progression-free survival (mPFS) was 5.8 months (95% CI 3.9-7.3). Patients pretreated with fulvestrant had a similar PFS of 6.4 months (HR 1.00; 95% CI 0.55-1.83; P = 1.00). The most common AEs (adverse events) were neutropenia (93%), anemia (65%), and thrombocytopenia (55%). In this heavily pretreated population including everolimus, fulvestrant plus palbociclib provides an mPFS of 5.8 months with the same magnitude of benefit for fulvestrant-pretreated patients.

  14. Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.

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    Raphael, J; Helou, J; Pritchard, K I; Naimark, D M

    2017-11-01

    The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer

    International Nuclear Information System (INIS)

    Tolaney, Sara M; Jeong, Joon; Guo, Hao; Brock, Jane; Morganstern, Daniel; Come, Steven E; Golshan, Mehra; Bellon, Jennifer; Winer, Eric P; Krop, Ian E

    2014-01-01

    Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m 2 daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer

  16. [Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015].

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    Vanacker, Hélène; Bally, Olivia; Kassem, Loay; Tredan, Olivier; Heudel, Pierre; Bachelot, Thomas

    2015-06-01

    Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

  17. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up

    DEFF Research Database (Denmark)

    Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita

    2011-01-01

    Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast...

  18. Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer.

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    Jankowitz, Rachel C; McGuire, Kandace P; Davidson, Nancy E

    2013-08-01

    Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects

  19. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  20. Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

    International Nuclear Information System (INIS)

    Ritte, Rebecca; Grote, Verena; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Berrino, Franco; Mattiello, Amalia; Tumino, Rosario; Tikk, Kaja; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, H Bas; Gils, Carla H van; Peeters, Petra HM; Lukanova, Annekatrin; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Tjønneland, Anne; Rinaldi, Sabina; Vineis, Paulo; Merritt, Melissa A; Riboli, Elio; Kaaks, Rudolf; Olsen, Anja; Overvad, Kim; Dossus, Laure; Fournier, Agnès; Clavel-Chapelon, Françoise

    2013-01-01

    The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p trend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p trend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p het = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant

  1. Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer.

    Science.gov (United States)

    Mangini, Neha S; Wesolowski, Robert; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B; Berger, Michael J

    2015-11-01

    To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer. Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts. In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001). Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer. © The Author(s) 2015.

  2. The ability of PAM50 risk of recurrence score to predict 10-year distant recurrence in hormone receptor-positive postmenopausal women with special histological subtypes

    DEFF Research Database (Denmark)

    Laenkholm, Anne-Vibeke; Jensen, Maj-Britt; Eriksen, Jens Ole

    2018-01-01

    INTRODUCTION: The Prosigna-PAM50 risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR) in hormone receptor-positive breast cancer. Here, we examine the ability of Prosigna for predicting DR at 10 years in a subgroup of postmenop...

  3. CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark

    2015-01-01

    To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1...

  4. Clinical implications of recent studies using mTOR inhibitors to treat advanced hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Arena, Francis

    2014-01-01

    Breast cancer is a leading cause of cancer-related death worldwide. Approximately 75% of breast cancer is hormone receptor-positive (HR + ) and is managed with endocrine therapies. However, relapse or disease progression caused by primary or acquired endocrine resistance is frequent. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)-mediated signaling is one of the molecular mechanisms leading to endocrine resistance. mTOR inhibitors that target the PI3K/Akt/mTOR pathway are the first of the targeted therapies to be evaluated in clinical trials to overcome endocrine resistance. Although the clinical trial with temsirolimus, an mTOR inhibitor, did not show any benefit when compared with endocrine therapy alone, a Phase II clinical trial with sirolimus has been promising. Recently, everolimus was approved in combination with exemestane by the US Food and Drug Administration for treating postmenopausal women with advanced HR + breast cancer, based on the results of a Phase III trial. Therefore, everolimus represents the first and only targeted agent approved for combating endocrine resistance

  5. Breast cancer with Her-22 hormone receptor-positive neu: primary systemic treatment, sentinel node biopsy and hormone

    International Nuclear Information System (INIS)

    Lopez C, Nayara; Sanchez M, Jose Ignacio; De Santiago G, Javier

    2013-01-01

    Neoadjuvant chemotherapy is an interesting option in the therapy of some breast cancer cases. Cases in which the timing for sentinel lymph node biopsy is controversial. Co-expression of estrogen receptors and Her2/neu (cc-erbB-2) in breast cancer may imply hormone resistance, especially to tamoxifen. We present a clinic case with co-expression of estrogen receptors and Her2/neu that was treated with neoadjuvant chemotherapy and previous sentinel lymph node biopsy followed by breast tumorectomy with axillar lympha- denectomy, radiotherapy and hormonotherapy with letrozol, geserelina and trastuzumab. A good treatment response as found

  6. Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy.

    Science.gov (United States)

    Bonechi, Martina; Galardi, Francesca; Biagioni, Chiara; De Luca, Francesca; Bergqvist, Mattias; Neumüller, Magnus; Guarducci, Cristina; Boccalini, Giulia; Gabellini, Stefano; Migliaccio, Ilenia; Di Leo, Angelo; Pestrin, Marta; Malorni, Luca

    2018-03-27

    The aim of this study was to investigate if thymidine kinase-1 (TK1), a well-known proliferation marker, could represent a valid circulating biomarker to identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic breast cancer (MBC) patients most likely to benefit from endocrine therapy (ET). We used the DiviTum™ assay to analyze TK1 activity in cell lysates of three HR+/HER2neg BC cell lines and in plasma of 31 HR+/HER2neg MBC patients receiving ET. Blood samples were collected at treatment initiation, after one month and at disease progression. CTCs count and ESR1 / PIK3CA mutations in circulating tumor DNA were performed and correlated with TK1 activity. TK1 activity was reduced in the two endocrine-sensitive cell lines after 2 days of treatment. In patients, high baseline TK1 activity correlated with CTCs positivity (p-value=0.014). Patients with low baseline levels of TK1 activity had a significantly better PFS compared to those with high baseline TK1 activity (p-value=0.012). Patients with an early drop of TK1 activity after one month of treatment had a significantly better PFS compared to those who experienced an increase (p-value=0.0026). Our study suggests that TK1 could be a potential prognostic, predictive and monitoring marker of early ET response in HR+/HER2neg MBC patients.

  7. Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

    Science.gov (United States)

    Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

    2014-01-01

    Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

  8. Understanding discontinuation of oral adjuvant endocrine therapy by women with hormone receptor-positive invasive breast cancer nearly 4 years from diagnosis.

    Science.gov (United States)

    Bell, Robin J; Fradkin, Pamela; Schwarz, Max; Davis, Susan R

    2013-01-01

    The aim of this study was to investigate the extent of discontinuation of oral adjuvant endocrine therapy (OAET) in women nearly 4 years from the diagnosis of their first episode of invasive breast cancer and the reasons for such discontinuation. We used a large, prospective cohort study of women who had been diagnosed with their first episode of invasive breast cancer between 2004 and 2006, recruited through a state-based cancer registry. All participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQs) thereafter. The data in this report were obtained from the EQ and the first three FQs. A total of 1,370 women with hormone receptor-positive disease completed the EQ. At the completion of the third FQ nearly 4 years from diagnosis, 1,193 women remained in the study. Use of OAET peaked by 2 years postdiagnosis. At nearly 4 years from diagnosis, 18% of the 1,193 women remaining in the study were not taking OAET. Of these women, just more than half had ceased therapy mainly owing to a range of adverse effects, predominantly estrogen deficiency symptoms, but the remainder (8% of women remaining in the study) had never used OAET. Our study confirms that early discontinuation of OAET due to estrogen deficiency symptoms remains an important issue despite calls for strategies to address this problem. The number of women potentially suitable for OAET but not receiving it was almost as great as the number of those who have discontinued therapy.

  9. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study.

    Science.gov (United States)

    Ritte, Rebecca; Lukanova, Annekatrin; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Mesrine, Sylvie; Fagherazzi, Guy; Dossus, Laure; Teucher, Birgit; Steindorf, Karen; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, Bas; van Duijnhoven, Franzel; van Gils, Carla H; Peeters, Petra Hm; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Krum-Hansen, Sanda; Gram, Inger Torhild; Lund, Eiliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Rinaldi, Sabina; McCormack, Valerie; Riboli, Elio; Kaaks, Rudolf

    2013-06-01

    Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER-PR-) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and -negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. Copyright © 2012 UICC.

  10. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    International Nuclear Information System (INIS)

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

  11. Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

    DEFF Research Database (Denmark)

    Frogne, Thomas; Laenkholm, Anne-Vibeke; Lyng, Maria B

    2009-01-01

    INTRODUCTION: High expression of total HER2 protein confers poor prognosis for breast cancer patients. HER2 is a member of the HER family consisting of four receptors, HER1 to HER4. HER receptor activity is regulated by a variety of mechanisms, and phosphorylation of the C-terminal part of the HER...... metastases, by evaluating the expression of phosphorylated HER1, HER2, HER3, Erk, Akt and the total level of HER4 and HER2. METHODS: Immunohistochemical analysis was performed on 268 primary breast tumors and 30 paired metastatic lesions from postmenopausal women with hormone receptor-positive breast tumors...... of Akt and Erk were quite uniformly expressed in the categories; negative, moderate or strong. In univariate analysis, expression of total HER2, pHER1, pHER2 and pHER3 was significantly associated with poor disease-free survival. Strong HER4 expression was associated with prolonged disease-free as well...

  12. Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones.

    Science.gov (United States)

    Shieh, Yiwey; Hu, Donglei; Ma, Lin; Huntsman, Scott; Gard, Charlotte C; Leung, Jessica W T; Tice, Jeffrey A; Ziv, Elad; Kerlikowske, Karla; Cummings, Steven R

    2017-11-01

    Models that predict the risk of estrogen receptor (ER)-positive breast cancers may improve our ability to target chemoprevention. We investigated the contributions of sex hormones to the discrimination of the Breast Cancer Surveillance Consortium (BCSC) risk model and a polygenic risk score comprised of 83 single nucleotide polymorphisms. We conducted a nested case-control study of 110 women with ER-positive breast cancers and 214 matched controls within a mammography screening cohort. Participants were postmenopausal and not on hormonal therapy. The associations of estradiol, estrone, testosterone, and sex hormone binding globulin with ER-positive breast cancer were evaluated using conditional logistic regression. We assessed the individual and combined discrimination of estradiol, the BCSC risk score, and polygenic risk score using the area under the receiver operating characteristic curve (AUROC). Of the sex hormones assessed, estradiol (OR 3.64, 95% CI 1.64-8.06 for top vs bottom quartile), and to a lesser degree estrone, was most strongly associated with ER-positive breast cancer in unadjusted analysis. The BCSC risk score (OR 1.32, 95% CI 1.00-1.75 per 1% increase) and polygenic risk score (OR 1.58, 95% CI 1.06-2.36 per standard deviation) were also associated with ER-positive cancers. A model containing the BCSC risk score, polygenic risk score, and estradiol levels showed good discrimination for ER-positive cancers (AUROC 0.72, 95% CI 0.65-0.79), representing a significant improvement over the BCSC risk score (AUROC 0.58, 95% CI 0.50-0.65). Adding estradiol and a polygenic risk score to a clinical risk model improves discrimination for postmenopausal ER-positive breast cancers.

  13. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Leissner, Philippe; Verjat, Thibault; Bachelot, Thomas; Paye, Malick; Krause, Alexander; Puisieux, Alain; Mougin, Bruno

    2006-01-01

    One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

  14. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Krause Alexander

    2006-08-01

    Full Text Available Abstract Background One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1. In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. Methods The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. Results uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS and Breast Cancer specific Survival (BCS were significantly shorter in patients expressing high levels of PAI-1 mRNA (p PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR = 10.12; p = 0.0002 and for BCS (HR = 13.17; p = 0.0003. Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41 nor with BCS (p = 0.19. In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. Conclusion These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.

  15. Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

    Science.gov (United States)

    Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

    2008-09-01

    Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

  16. Influence of exogenous lactoferrin on the oxidant/antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro.

    Science.gov (United States)

    Zalutskii, I V; Lukianova, N Y; Storchai, D M; Burlaka, A P; Shvets, Y V; Borikun, T V; Todor, I M; Lukashevich, V S; Rudnichenko, Y A; Chekhun, V F

    2017-07-01

    To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of "free" iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4-1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14-24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, "free" iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.

  17. Endocrine Therapy of Estrogen Receptor-Positive Breast Cancer Cells: Early Differential Effects on Stem Cell Markers

    Directory of Open Access Journals (Sweden)

    Euphemia Y. Leung

    2017-09-01

    Full Text Available IntroductionEndocrine therapy of breast cancer, which either deprives cancer tissue of estrogen or prevents estrogen pathway signaling, is the most common treatment after surgery and radiotherapy. We have previously shown for the estrogen-responsive MCF-7 cell line that exposure to tamoxifen, or deprivation of estrogen, leads initially to inhibition of cell proliferation, followed after several months by the emergence of resistant sub-lines that are phenotypically different from the parental line. We examined the early responses of MCF-7 cells following either exposure to 4-hydroxytamoxifen or deprivation of estrogen for periods of 2 days–4 weeks.MethodsEndocrine-sensitive or -resistant breast cancer cell lines were used to examine the expression of the stem cell gene SOX2, and the Wnt effector genes AXIN2 and DKK1 using quantitative PCR analysis. Breast cancer cell lines were used to assess the anti-proliferative effects (as determined by IC50 values of Wnt pathway inhibitors LGK974 and IWP-2.ResultsHormone therapy led to time-dependent increases of up to 10-fold in SOX2 expression, up to threefold in expression of the Wnt target genes AXIN2 and DKK1, and variable changes in NANOG and OCT4 expression. The cells also showed increased mammosphere formation and increased CD24 surface protein expression. Some but not all hormone-resistant MCF-7 sub-lines, emerging after long-term hormonal stress, showed up to 50-fold increases in SOX2 expression and smaller increases in AXIN2 and DKK1 expression. However, the increase in Wnt target gene expression was not accompanied by an increase in sensitivity to Wnt pathway inhibitors LGK974 and IWP-2. A general trend of lower IC50 values was observed in 3-dimensional spheroid culture conditions (which allowed enrichment of cells with cancer stem cell phenotype relative to monolayer cultures. The endocrine-resistant cell lines showed no significant increase in sensitivity to Wnt inhibitors.ConclusionHormone

  18. Personal and clinical social support and adherence to adjuvant endocrine therapy among hormone receptor-positive breast cancer patients in an integrated health care system.

    Science.gov (United States)

    Kroenke, Candyce H; Hershman, Dawn L; Gomez, Scarlett L; Adams, Sara R; Eldridge, Elizabeth H; Kwan, Marilyn L; Ergas, Isaac J; Kubo, Ai; Kushi, Lawrence H

    2018-04-18

    We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients' personal support was moderate or low (P value = 0.04). Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence.

  19. Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

    Science.gov (United States)

    Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

    2016-01-01

    Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

  20. Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

    Science.gov (United States)

    André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

    2014-06-01

    International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

  1. De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

    Science.gov (United States)

    Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

    2017-09-10

    Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

  2. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.

    Science.gov (United States)

    Noguchi, Shinzaburo; Masuda, Norikazu; Iwata, Hiroji; Mukai, Hirofumi; Horiguchi, Jun; Puttawibul, Puttisak; Srimuninnimit, Vichien; Tokuda, Yutaka; Kuroi, Katsumasa; Iwase, Hirotaka; Inaji, Hideo; Ohsumi, Shozo; Noh, Woo-Chul; Nakayama, Takahiro; Ohno, Shinji; Rai, Yoshiaki; Park, Byeong-Woo; Panneerselvam, Ashok; El-Hashimy, Mona; Taran, Tetiana; Sahmoud, Tarek; Ito, Yoshinori

    2014-11-01

    The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

  3. Utility of the CPS+EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Marmé, Frederik; Lederer, Bianca; Blohmer, Jens-Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kümmel, Sherko; Loibl, Sibylle; Paepke, Stefan; Untch, Michael; von Minckwitz, Gunter; Schneeweiss, Andreas

    2016-01-01

    Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients. The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials. Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population. In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

    Science.gov (United States)

    Pritchard, Kathleen I; Burris, Howard A; Ito, Yoshinori; Rugo, Hope S; Dakhil, Shaker; Hortobagyi, Gabriel N; Campone, Mario; Csöszi, Tibor; Baselga, José; Puttawibul, Puttisak; Piccart, Martine; Heng, Daniel; Noguchi, Shinzaburo; Srimuninnimit, Vichien; Bourgeois, Hugues; Gonzalez Martin, Antonio; Osborne, Karen; Panneerselvam, Ashok; Taran, Tetiana; Sahmoud, Tarek; Gnant, Michael

    2013-12-01

    Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    Science.gov (United States)

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total

  6. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fowble, B; Fein, D A; Hanlon, A L; Eisenberg, B L; Hoffman, J P; Sigurdson, E R; Daly, M B; Goldstein, L J

    1995-07-01

    Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

  7. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

    1995-01-01

    Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

  8. Postmenopausal Serum Sex Steroids and Risk of Hormone Receptor-Positive and -Negative Breast Cancer : a Nested Case-Control Study

    NARCIS (Netherlands)

    James, Rebecca E.; Lukanova, Annekatrin; Dossus, Laure; Becker, Susen; Rinaldi, Sabina; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Mesrine, Sylvie; Engel, Pierre; Clavel-Chapelon, Francoise; Chang-Claude, Jenny; Vrieling, Alina; Boeing, Heiner; Schuetze, Madlen; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Rodriguez, Laudina; Buckland, Genevieve; Sanchez, Maria-Jose; Amiano, Pilar; Ardanaz, Eva; Bueno-de-Mesquita, Bas; Ros, Martine M.; van Gils, Carla H.; Peeters, Petra H.; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J.; Allen, Naomi E.; Romieu, Isabelle; Siddiq, Afshan; Cox, David; Riboli, Elio; Kaaks, Rudolf

    2011-01-01

    Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of

  9. Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study

    NARCIS (Netherlands)

    James, R.E.; Lukanova, A.; Dossus, L.; Becker, S.; Rinaldi, S.; Tjonneland, A.; Olsen, A.; Overvad, K.; Mesrine, S.; Engel, P.; Clavel-Chapelon, F.; Chang-Claude, J.; Vrieling, A.; Boeing, H.; Schutze, M.; Trichopoulou, A.; Lagiou, P.; Trichopoulos, D.; Palli, D.; Krogh, V.; Panico, S.; Tumino, R.; Sacerdote, C.; Rodriguez, L.; Buckland, G.; Sanchez, M.J.; Amiano, P.; Ardanaz, E.; Bueno-de-Mesquita, B.; Ros, M.M.; Gils, C.H. van; Peeters, P.H.M.; Khaw, K.T.; Wareham, N.; Key, T.J.; Allen, N.E.; Romieu, I.; Siddiq, A.; Cox, D.; Riboli, E.; Kaaks, R.

    2011-01-01

    Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of

  10. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

    Science.gov (United States)

    Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

    2015-06-01

    Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p anxiety about the selected adjuvant therapy decreased with use of the GEP.

  11. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald

    2014-01-01

    INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether these altera...... and could potentially be used to monitor whether all cancer cells have been removed at surgery and/or, subsequently, whether the patients develop recurrence.......INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether...... these alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...

  12. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

    Science.gov (United States)

    Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Coates, Alan S; Thürlimann, Beat

    2011-11-01

    Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years

  13. Hormone patterns in early human gestation

    International Nuclear Information System (INIS)

    Mishell, D.R. Jr.; Thorneycroft, I.H.; Nagata, Y.; Murata, T.; Nakamura, R.M.

    1974-01-01

    Accurate measurement of the low concentration of gonadotropins and steroid hormones present in human serum has been made possible by the development of sensitive radioimmunoassay (RIA) techniques. With the use of RIA FSH and LH, progesterone and 17OH-progesterone have been previously measured in early normal pregnancy. In order to determine the daily pattern of hormone levels in early normal pregnancy, gonadotropins as well as steroid hormone levels were measured in serum samples obtained daily from three women from the time of the last menstrual period prior to conception throughout the first few months of gestation. To further identify the steroid hormone pattern in early normal pregnancy, concentrations of estradiol, progesterone, and 17OH-progesterone were measured in individual serum samples obtained from a group of 158 women with apparently normal gestations who subsequently had therapeutic abortions. (auth)

  14. Progranulin as a prognostic biomarker for breast cancer recurrence in patients who had hormone receptor-positive tumors: a cohort study.

    Directory of Open Access Journals (Sweden)

    Dong Hoe Koo

    Full Text Available Progranulin (PGRN is considered to play an important role in breast cancer tumorigenesis and in inhibiting tamoxifen-induced apoptosis. We aimed to determine whether PGRN levels are associated with breast cancer recurrence after curative surgery.We evaluated the associations between preoperative serum PGRN levels and breast cancer recurrence in a cohort of 697 newly diagnosed breast cancer patients who underwent curative surgery between April 2001 and December 2004. The mean age ± standard deviation (SD was 46 ± 9.8 years, and all patients with hormone receptor (HR-positive tumors received adjuvant tamoxifen therapy. At a median follow-up of 62.2 months (range, 2.9-98.2, 89 patients (12.8% had experienced a recurrence and 51 patients (7.3% had died. In the HR-positive group, serum PGRN levels were associated with recurrence according to the log-rank test for trend (p for trend = 0.049. There was no association between PGRN levels and recurrence in the HR-negative group (p for trend = 0.658. Adjusted hazard ratios, including possible confounders, revealed a linear relationship between serum PGRN levels and recurrence in the HR-positive group (p for trend = 0.049, and this association was further strengthened after excluding patients who had no lymph node metastasis (p for trend = 0.038.Serum PGRN levels were clinically significant for predicting recurrence in patients with HR-positive breast cancer during adjuvant tamoxifen therapy.

  15. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

    Science.gov (United States)

    Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

    2015-09-01

    Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

    Science.gov (United States)

    Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

    2018-05-04

    The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

  17. Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

    Science.gov (United States)

    Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

    2018-05-01

    The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

  18. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

    Science.gov (United States)

    Johnston, Stephen Rd; Kilburn, Lucy S; Ellis, Paul; Dodwell, David; Cameron, David; Hayward, Larry; Im, Young-Hyuck; Braybrooke, Jeremy P; Brunt, A Murray; Cheung, Kwok-Leung; Jyothirmayi, Rema; Robinson, Anne; Wardley, Andrew M; Wheatley, Duncan; Howell, Anthony; Coombes, Gill; Sergenson, Nicole; Sin, Hui-Jung; Folkerd, Elizabeth; Dowsett, Mitch; Bliss, Judith M

    2013-09-01

    The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to

  19. HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wen-Tsung Huang

    2017-12-01

    Full Text Available Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+ breast cancer patients. Even though dysregulations of histone deacetylases (HDACs are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

  20. Hormonal responses during early embryogenesis in maize.

    Science.gov (United States)

    Chen, Junyi; Lausser, Andreas; Dresselhaus, Thomas

    2014-04-01

    Plant hormones have been shown to regulate key processes during embryogenesis in the model plant Arabidopsis thaliana, but the mechanisms that determine the peculiar embryo pattern formation of monocots are largely unknown. Using the auxin and cytokinin response markers DR5 and TCSv2 (two-component system, cytokinin-responsive promoter version #2), as well as the auxin efflux carrier protein PIN1a (PINFORMED1a), we have studied the hormonal response during early embryogenesis (zygote towards transition stage) in the model and crop plant maize. Compared with the hormonal response in Arabidopsis, we found that detectable hormone activities inside the developing maize embryo appeared much later. Our observations indicate further an important role of auxin, PIN1a and cytokinin in endosperm formation shortly after fertilization. Apparent auxin signals within adaxial endosperm cells and cytokinin responses in the basal endosperm transfer layer as well as chalazal endosperm are characteristic for early seed development in maize. Moreover, auxin signalling in endosperm cells is likely to be involved in exogenous embryo patterning as auxin responses in the endosperm located around the embryo proper correlate with adaxial embryo differentiation and outgrowth. Overall, the comparison between Arabidopsis and maize hormone response and flux suggests intriguing mechanisms in monocots that are used to direct their embryo patterning, which is significantly different from that of eudicots.

  1. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial.

    Science.gov (United States)

    Rugo, Hope S; Seneviratne, Lasika; Beck, J Thaddeus; Glaspy, John A; Peguero, Julio A; Pluard, Timothy J; Dhillon, Navneet; Hwang, Leon Christopher; Nangia, Chaitali; Mayer, Ingrid A; Meiller, Timothy F; Chambers, Mark S; Sweetman, Robert W; Sabo, J Randy; Litton, Jennifer K

    2017-05-01

    Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer. Beginning on day 1 of cycle 1, patients received everolimus 10 mg plus exemestane 25 mg daily, with 10 mL of alcohol-free dexamethasone 0·5 mg per 5 mL oral solution (swish for 2 min and spit, four times daily for 8 weeks). After 8 weeks, dexamethasone mouthwash could be continued for up to eight additional weeks at the discretion of the clinician and patient. The primary endpoint was incidence of grade 2 or worse stomatitis by 8 weeks assessed in the full analysis set (patients who received at least one dose of everolimus and exemestane and at least one confirmed dose of dexamethasone mouthwash) versus historical controls from the BOLERO-2 trial (everolimus and exemestane treatment in patients with hormone receptor-positive advanced breast cancer who were not given dexamethasone mouthwash for prevention of stomatitis). This trial is registered at ClinicalTrials.gov, number NCT02069093. Between May 28, 2014, and Oct 8, 2015, we enrolled 92 women; 85 were evaluable for efficacy. By 8 weeks, the incidence of grade 2 or worse stomatitis was two (2%) of 85 patients (95% CI 0·29-8·24), versus 159 (33%) of 482 patients (95% CI 28·8-37·4) for the duration of the BOLERO-2 study. Overall, 83 (90%) of 92 patients had at least one adverse event. The most frequently

  2. Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

    Science.gov (United States)

    Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

    2017-06-01

    The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

  3. Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

    Science.gov (United States)

    Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

    2013-02-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

  4. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, Barbara; Fein, Douglas A.; Hanlon, Alexandra L.; Eisenberg, Burton L.; Hoffman, John P.; Sigurdson, Elin R.; Daly, Mary B.; Goldstein, Lori J.

    1996-01-01

    Purpose: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. Methods and Materials: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of the patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. Results: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of reexcision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all

  5. How Early Hormones Shape Gender Development

    Science.gov (United States)

    Berenbaum, Sheri A.; Beltz, Adriene M.

    2015-01-01

    Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression. PMID:26688827

  6. Health-related quality of life from the FALCON phase III randomised trial of fulvestrant 500 mg versus anastrozole for hormone receptor-positive advanced breast cancer.

    Science.gov (United States)

    Robertson, John F R; Cheung, Kwok-Leung; Noguchi, Shinzaburo; Shao, Zhimin; Degboe, Arnold; Lichfield, Jasmine; Thirlwell, Jackie; Fazal, Mehdi; Ellis, Matthew J

    2018-05-01

    The phase III randomised FALCON trial (NCT01602380) demonstrated improved progression-free survival with fulvestrant 500 mg versus anastrozole 1 mg in endocrine therapy-naïve postmenopausal women with hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC). Furthermore, overall health-related quality of life (HRQoL) was maintained and comparable for fulvestrant and anastrozole. Here, we present additional analyses of patient-reported HRQoL outcomes from FALCON. Women with endocrine therapy-naïve HR+ LA/MBC were randomised 1:1 to fulvestrant (days 0, 14, 28, then every 28 d) or anastrozole (daily) until disease progression or discontinuation. HRQoL was assessed by FACT-B questionnaire (TOI and FACT-B total score) at randomisation and every 12 weeks during treatment. HRQoL data post-treatment (with or without progression) were also collected. In total, 462 patients were randomised (fulvestrant, n = 230; anastrozole, n = 232). Compliance to FACT-B overall ranged from 60.0 to 97.4%. Mean change from baseline in TOI and FACT-B total score remained broadly stable (approximately ± 3 points to week 132) and was similar between arms during treatment. HRQoL was also maintained in FACT-B subscales. Approximately one-third of patients had improved TOI (≥+6 points) and FACT-B (≥+8 points) total scores from baseline up to week 120 and 132, respectively, of treatment with fulvestrant (ranges 26.4-45.0% and 22.4-35.8%, respectively) and anastrozole (ranges 18.6-32.9%, and 22.7-37.9%, respectively). Mean change from baseline in TOI and FACT-B total score was maintained for fulvestrant and anastrozole; similar proportions of patients in both arms had improved TOI and FACT-B total scores. CLINICALTRIALS. NCT01602380. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial.

    Science.gov (United States)

    Harbeck, N; Iyer, S; Turner, N; Cristofanilli, M; Ro, J; André, F; Loi, S; Verma, S; Iwata, H; Bhattacharyya, H; Puyana Theall, K; Bartlett, C H; Loibl, S

    2016-06-01

    In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5-67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (-3.3, 95% CI -5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with fulvestrant alone. Palbociclib plus fulvestrant allowed patients to maintain good Qo

  8. PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor–Positive Early Breast Cancer

    DEFF Research Database (Denmark)

    Lænkholm, Anne Vibeke; Jensen, M.B.; Eriksen, J O

    2018-01-01

    with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were...... treated with endocrine therapy for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna and, after determination of human epidermal growth factor receptor 2 (HER2) status, data from 2,558 hormone receptor-positive/HER2-negative samples were analyzed, including 1,395 node...

  9. Cost-effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in women with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer

    International Nuclear Information System (INIS)

    Hannouf, Malek B; Xie, Bin; Brackstone, Muriel; Zaric, Gregory S

    2012-01-01

    A 21-gene recurrence score (RS) assay may inform adjuvant systematic treatment decisions in women with early stage breast cancer. We sought to investigate the cost effectiveness of using the RS-assay versus current clinical practice (CCP) in women with early-stage estrogen- or progesterone-receptor-positive, axilliary lymph-node negative breast cancer (ER+/ PR + LN- ESBC) from the perspective of the Canadian public healthcare system. We developed a Markov model to project the lifetime clinical and economic consequences of ESBC. We evaluated adjuvant therapy separately in post- and pre-menopausal women with ER+/ PR + LN- ESBC. We assumed that the RS-assay would reclassify pre- and post-menopausal women among risk levels (low, intermediate and high) and guide adjuvant systematic treatment decisions. The model was parameterized using 7 year follow up data from the Manitoba Cancer Registry, cost data from Manitoba administrative databases, and secondary sources. Costs are presented in 2010 CAD. Future costs and benefits were discounted at 5%. The RS-assay compared to CCP generated cost-savings in pre-menopausal women and had an ICER of $60,000 per QALY gained in post-menopausal women. The cost effectiveness was most sensitive to the proportion of women classified as intermediate risk by the RS-assay who receive adjuvant chemotherapy and the risk of relapse in the RS-assay model. The RS-assay is likely to be cost effective in the Canadian healthcare system and should be considered for adoption in women with ER+/ PR + LN- ESBC. However, ongoing assessment and validation of the assay in real-world clinical practice is warranted

  10. Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study.

    Science.gov (United States)

    Gligorov, Joseph; Pivot, Xavier B; Jacot, William; Naman, Hervé L; Spaeth, Dominique; Misset, Jean-Louis; Largillier, Rémy; Sautiere, Jean-Loup; de Roquancourt, Anne; Pomel, Christophe; Rouanet, Philippe; Rouzier, Roman; Penault-Llorca, Frederique M

    2015-08-01

    The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians' confidence before and after knowing the Recurrence Score value, and physicians' perception of the assay were recorded. Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians' confidence improved significantly. These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies. ©AlphaMed Press.

  11. Early growth and postprandial appetite regulatory hormone responses

    DEFF Research Database (Denmark)

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M

    2013-01-01

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore......, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life......, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels....

  12. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer

    DEFF Research Database (Denmark)

    Smith, Ian; Yardley, Denise; Burris, Howard

    2017-01-01

    receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709.......9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR...

  13. Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).

    Science.gov (United States)

    Verma, Sunil; Bartlett, Cynthia Huang; Schnell, Patrick; DeMichele, Angela M; Loi, Sherene; Ro, Jungsil; Colleoni, Marco; Iwata, Hiroji; Harbeck, Nadia; Cristofanilli, Massimo; Zhang, Ke; Thiele, Alexandra; Turner, Nicholas C; Rugo, Hope S

    2016-10-01

    Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed

  14. Alterations of the genes involved in the PI3K and estrogen-receptor pathways influence outcome in human epidermal growth factor receptor 2-positive and hormone receptor-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Takada, Mamoru; Miyazaki, Masaru; Sato-Otsubo, Aiko; Ogawa, Seishi; Kaneko, Yasuhiko; Higuchi, Toru; Tozuka, Katsunori; Takei, Hiroyuki; Haruta, Masayuki; Watanabe, Junko; Kasai, Fumio; Inoue, Kenichi; Kurosumi, Masafumi

    2013-01-01

    Chemotherapy with trastuzumab is widely used for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated. Genomic alterations were analyzed using single-nucleotide polymorphism arrays in 46 HER2 immunohistochemistry (IHC) 3+ or 2+/fluorescent in situ hybridization (FISH)+ breast cancers that were treated with neoadjuvant chemotherapy with paclitaxel, cyclophosphamid, epirubicin, fluorouracil, and trastuzumab. Patients were classified into two groups based on presence or absence of alterations of 65 cancer-associated genes, and the two groups were further classified into four groups based on genomic HER2 copy numbers or hormone receptor status (HR+/−). Pathological complete response (pCR) and relapse-free survival (RFS) rates were compared between any two of the groups. The pCR rate was 54% in 37 patients, and the RFS rate at 3 years was 72% (95% CI, 0.55-0.89) in 42 patients. The analysis disclosed 8 tumors with nonamplified HER2 and 38 tumors with HER2 amplification, indicating the presence of discordance in tumors diagnosed using current HER2 testing. The 8 patients showed more difficulty in achieving pCR (P=0.019), more frequent relapse (P=0.018), and more frequent alterations of genes in the PI3K pathway (P=0.009) than the patients with HER2 amplification. The alterations of the PI3K and estrogen receptor (ER) pathway genes generally indicated worse RFS rates. The prognostic significance of the alterations was shown in patients with a HR+ tumor, but not in patients with a HR- tumor when divided. Alterations of the PI3K and ER pathway genes found in patients with a HR+ tumor with poor outcome suggested that crosstalk between the two pathways may be involved in resistance to the current chemotherapy with trastuzumab. We

  15. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

    Science.gov (United States)

    Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-08-01

    To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  16. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

    Science.gov (United States)

    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were

  17. [Early sibling aggression in mammals and its hormonal correlates].

    Science.gov (United States)

    Antonevich, A L; Naĭdenko, S V

    2007-01-01

    Early sibling aggression is a widespread phenomenon in birds. Ornithologists distinguish species with "obligate" and "facultative" siblicide. Sibling aggression was described in some mammal species: the domestic pig (Sus scrofa), the spotted hyena (Crocuta crocuta), the Eurasian lynx (Lynx lynx), and the Iberian lynx (L. par-dinus). In all of them, sibling aggression corresponds well with the "facultative" siblicide model in birds. Sibling aggression was observed at the age of 36-64 days in both lynx species. It is usually restricted to a single fight and can change the hierarchical structure and growth rate of the kittens. In the spotted hyena and the domestic pig, the frequency and intensity of aggressive interactions between siblings are strongest during the first days of postnatal ontogeny and then decrease gradually. The newborns of these species are much developed than newborn lynx kittens. Usually adult lynx females, in contrast to hyenas and pigs, try to stop sibling fights. This is probably related to the larger parental investment at the time of the fight in lynxes (a kitten's body weight is about 10% of the mother's) than in pigs (0.5%) and hyenas (1.9%). Sibling aggression in spotted hyenas could be related to the high level of androstenedione and is not related to testosterone concentration. In the Eurasian lynx, female sibs attack their littermates slightly more often than male sibs do, and sibling aggression is not testosterone-dependent. Hormones secreted by the adrenal glands may play an important role in this phenomenon. The data available so far, however, do not positively confirm the presence of hormonal trigger effects in mammal sibling aggression.

  18. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-01-01

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  19. Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

    Science.gov (United States)

    Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

    2016-07-02

    The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

  20. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  1. Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers.

    Directory of Open Access Journals (Sweden)

    Erica B Schleifman

    Full Text Available Patients with newly diagnosed, early stage estrogen receptor positive (ER+ breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies.

  2. Infantile and early childhood masturbation: Sex hormones and clinical profile.

    Science.gov (United States)

    Ajlouni, Heitham K; Daoud, Azhar S; Ajlouni, Saleh F; Ajlouni, Kamel M

    2010-01-01

    Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings.

  3. The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen Christine Leth; Andersen, Zorana Jovanovic; Heitmann, Berit Lilienthal

    2006-01-01

    Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether...... HT reduces this risk associated with early menopause....

  4. Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

    Science.gov (United States)

    Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

    2014-06-01

    The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

  5. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    Directory of Open Access Journals (Sweden)

    Janice K V Tam

    Full Text Available The evolutionary trajectories of growth hormone-releasing hormone (GHRH receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2 in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP receptor (PRPR. In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2 in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2 was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2 had the highest expression in brain, and interestingly, X. laevis(GHRHR2 also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2, which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP.

  6. Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

    Science.gov (United States)

    Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

    1996-08-01

    The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

  7. Sex hormones in early infancy seem to predict aspects of later language development.

    Science.gov (United States)

    Schaadt, Gesa; Hesse, Volker; Friederici, Angela D

    2015-02-01

    Sex differences in the development of cognitive behavior such as language have long been of great research interest. Lately, researchers have started to associate language function and brain differences with diverse sex hormones (e.g., testosterone/estradiol). However, results concerning the impact of early postnatal sex hormone concentration on the child's later language development are rare. Here, we analyze the impact of testosterone and estradiol in girls and boys as well as their neurophysiological phonemic discrimination at age 5months on language development at age 4years. Interestingly, we found strong positive estradiol and negative testosterone impact on later language performance at age 4years, which was true for both girls and boys. These results demonstrate that postnatal sex hormone surge might be viewed as one factor determining later language development, independent of gender. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones.

    Directory of Open Access Journals (Sweden)

    Po-Chin Huang

    Full Text Available Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy.We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, mono-(2-ethylhexyl phthalate (MEHP, mono-butyl phthalate (MnBP, of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4, free T4, and thyroid-binding globulin (TBG.Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%, MnBP (81% and MECPP (86%. Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97 in pregnant women using Bonferroni correction.We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

  9. Influence Of Feminine Hormones On Some Biochemical Parameters In Early And Late Menopausal Status

    International Nuclear Information System (INIS)

    KAMAL, A.M.

    2009-01-01

    Forty two healthy Egyptian women were participated in this study to evaluate the effect of early and late menopause on some biochemical and hormonal parameters. The women were divided into three equal groups. The first was the pre-menopausal group with regular menstrual cycle, the second was the late menopausal group comprised the menopausal female less than 5 years and the third group consisted of women that became menopause since 5-9 years. The second and third groups had almost the same age and body weight. After clinical examination, fasting blood samples were collected from all volunteers. Regarding the pre-menopausal women, blood was withdrawn between the 3 rd and the 5 th day post-menstruation (follicular phase). Follicle stimulating hormone (FSH), leutinizing hormone (LH), progesterone, prolactin (PRL), testosterone, leptin and thyroxine (T4) in addition to hemoglobin (Hb), blood glucose, calcium (Ca), inorganic phosphorous (P), magnesium (Mg) and uric acid were determined. Both menopausal groups showed significant increase in FSH and LH and significant decrease in PRL and late menopausal group experienced also multiple significant correlations between FSH, LH and other tested parameters. Prolongation of menopause exhibited decrease in leptin being significant as compared to pre-menopausal women than that experienced menopause at younger age. Due to the relation between leptin hormone and osteoporosis, the results of this investigation denoted that early cessation of annulations (menopause) in Egyptian women may lead to disturbance in bone metabolism causing inhibiting osteoblastogenesis and decreasing bone mass.

  10. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    International Nuclear Information System (INIS)

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel

    2005-01-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (≤6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment

  11. Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

    Science.gov (United States)

    Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

    2001-10-01

    To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

  12. Catch-up growth in early treated patients with growth hormone deficiency. Dutch Growth Hormone Working Group.

    OpenAIRE

    Boersma, B; Rikken, B; Wit, J M

    1995-01-01

    Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height S...

  13. Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata.

    Directory of Open Access Journals (Sweden)

    Shinji Yamaguchi

    Full Text Available Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3 peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4 in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

  14. Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata).

    Science.gov (United States)

    Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J

    2017-01-01

    Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

  15. Early onset diabetes-genetic and hormonal analysis in pakistan population

    International Nuclear Information System (INIS)

    Wahid, M.; Kamran, M.

    2016-01-01

    Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Results: Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. Conclusion: relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population. (author)

  16. Early prediction of post-thyroidectomy hypocalcemia by early parathyroid hormone measurement.

    Science.gov (United States)

    Yetkin, Gurkan; Citgez, Bulent; Yazici, Pinar; Mihmanli, Mehmet; Sit, Erhan; Uludag, Mehmet

    2016-01-01

    Hypoparathyroidism is the most common complication of total thyroidectomy (TT). Postthyroidectomy hypocalcemia occurs 24 to 48 hours after the operation. It prolongs the length of hospital stay, even though transient in most cases. The aim of this study was to predetermine the patients who may develop postthyroidectomy hypocalcemia by using early postoperative serum intact parathormone (iPTH) and calcium (Ca2+) measurements, and to investigate the effects of early initiated oral calcium and vitamin D treatments on the development of transient hypocalcemia. Patients who underwent TT after initiation of the early iPTH measurement protocol in January 2013 were included into the study group (Group 1, n=202). The control group (Group 2) was composed of 72 patients who underwent TT before the protocol. Prior to the initiation of the protocol, Ca2+ was measured instead of iPTH. In the study group, the serum Ca2+ and iPTH levels were measured before surgery, and 1 and 24-hours after. A calcium level below 8 mg/dL was accepted as biochemical hypocalcaemia, and a iPTH level under 15pg/mL was accepted as hypoparathyroidism. In the study group, patients with below normal iPTH levels were treated with prophylactic oral calcium and vitamin D. In Group 1, 15.8% (n=32) of the patients had hypoparathyroidism on the 1h and 24 h iPTH measurements. There was no statistically difference with regard to PTH levels measured in the postoperative 1st hour and at the 24th hour (p= 0.078). Biochemical hypocalcaemia developed in 16 (7.9%) and 13 (18%) patients in Groups 1 and 2, respectively, 24 hours after thyroidectomy (peffective management of plausible postthyroidectomic hypocalcemia. It yields significantly shorter hospital stay periods. Calcium, Hypoparathyroidism, Postoperative complication, Total thyroidectomy.

  17. 11q13 is a Susceptibility Locus for Hormone Receptor Positive Breast Cancer

    DEFF Research Database (Denmark)

    Lambrechts, Diether; Truong, Therese; Justenhoven, Christina

    2012-01-01

    genotyped the variants rs2380205, rs1011970, rs704010, rs614367, rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P = 3 × 10-9) and weak...

  18. Role of stress-related hormones in plant defence during early infection of the cyst nematode Heterodera schachtii in Arabidopsis

    Science.gov (United States)

    Kammerhofer, Nina; Radakovic, Zoran; Regis, Jully M A; Dobrev, Petre; Vankova, Radomira; Grundler, Florian M W; Siddique, Shahid; Hofmann, Julia; Wieczorek, Krzysztof

    2015-01-01

    Heterodera schachtii, a plant-parasitic cyst nematode, invades host roots and induces a specific syncytial feeding structure, from which it withdraws all required nutrients, causing severe yield losses. The system H. schachtii–Arabidopsis is an excellent research model for investigating plant defence mechanisms. Such responses are suppressed in well-established syncytia, whereas they are induced during early parasitism. However, the mechanisms by which the defence responses are modulated and the role of phytohormones are largely unknown. The aim of this study was to elucidate the role of hormone-based defence responses at the onset of nematode infection. First, concentrations of main phytohormones were quantified and the expression of several hormone-related genes was analysed using quantitative real-time (qRT)-PCR or GeneChip. Further, the effects of individual hormones were evaluated via nematode attraction and infection assays using plants with altered endogenous hormone concentrations. Our results suggest a pivotal and positive role for ethylene during nematode attraction, whereas jasmonic acid triggers early defence responses against H. schachtii. Salicylic acid seems to be a negative regulator during later syncytium and female development. We conclude that nematodes are able to impose specific changes in hormone pools, thus modulating hormone-based defence and signal transduction in strict dependence on their parasitism stage. PMID:25825039

  19. The development of fluoroandrogens and fluoroprogestins as potential imaging agents for receptor-positive prostate and breast tumors

    International Nuclear Information System (INIS)

    Brandes, S.J.; Katzenellenbogen, J.A.

    1986-01-01

    The assay of progesterone receptor (PR) concentration in breast tumors and androgen receptor (AR) concentration in prostate tumors enables hormone responsive neoplasms to be distinguished from those that are non-responsive. In principle, a positron-emitting progestin or androgen with suitably high affinity and selectivity for PR and AR, respectively, and an adequately high specific activity might provide a means for imaging receptor-positive tumors and quantifying their receptor content in vivo. The use of fluorine-18 as a radiolabel, coupled with the use of positron emission transaxial tomography, appears to be a most favorable approach in the development of receptor binding radiopharmaceuticals for in vivo imaging. Therefore, we have begun a systematic investigation of the development of fluorine-substituted androgens and progestins that might be prepared in F-18 labeled form as probes for AR and PR. (author)

  20. Delayed phenotypic expression of growth hormone transgenesis during early ontogeny in Atlantic salmon (Salmo salar?

    Directory of Open Access Journals (Sweden)

    Darek T R Moreau

    Full Text Available Should growth hormone (GH transgenic Atlantic salmon escape, there may be the potential for ecological and genetic impacts on wild populations. This study compared the developmental rate and respiratory metabolism of GH transgenic and non-transgenic full sibling Atlantic salmon during early ontogeny; a life history period of intense selection that may provide critical insight into the fitness consequences of escaped transgenics. Transgenesis did not affect the routine oxygen consumption of eyed embryos, newly hatched larvae or first-feeding juveniles. Moreover, the timing of early life history events was similar, with transgenic fish hatching less than one day earlier, on average, than their non-transgenic siblings. As the start of exogenous feeding neared, however, transgenic fish were somewhat developmentally behind, having more unused yolk and being slightly smaller than their non-transgenic siblings. Although such differences were found between transgenic and non-transgenic siblings, family differences were more important in explaining phenotypic variation. These findings suggest that biologically significant differences in fitness-related traits between GH transgenic and non-transgenic Atlantic salmon were less than family differences during the earliest life stages. The implications of these results are discussed in light of the ecological risk assessment of genetically modified animals.

  1. The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

    Science.gov (United States)

    Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

    2017-06-30

    Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A deep learning based strategy for identifying and associating mitotic activity with gene expression derived risk categories in estrogen receptor positive breast cancers.

    Science.gov (United States)

    Romo-Bucheli, David; Janowczyk, Andrew; Gilmore, Hannah; Romero, Eduardo; Madabhushi, Anant

    2017-06-01

    The treatment and management of early stage estrogen receptor positive (ER+) breast cancer is hindered by the difficulty in identifying patients who require adjuvant chemotherapy in contrast to those that will respond to hormonal therapy. To distinguish between the more and less aggressive breast tumors, which is a fundamental criterion for the selection of an appropriate treatment plan, Oncotype DX (ODX) and other gene expression tests are typically employed. While informative, these gene expression tests are expensive, tissue destructive, and require specialized facilities. Bloom-Richardson (BR) grade, the common scheme employed in breast cancer grading, has been shown to be correlated with the Oncotype DX risk score. Unfortunately, studies have also shown that the BR grade determined experiences notable inter-observer variability. One of the constituent categories in BR grading is the mitotic index. The goal of this study was to develop a deep learning (DL) classifier to identify mitotic figures from whole slides images of ER+ breast cancer, the hypothesis being that the number of mitoses identified by the DL classifier would correlate with the corresponding Oncotype DX risk categories. The mitosis detector yielded an average F-score of 0.556 in the AMIDA mitosis dataset using a 6-fold validation setup. For a cohort of 174 whole slide images with early stage ER+ breast cancer for which the corresponding Oncotype DX score was available, the distributions of the number of mitoses identified by the DL classifier was found to be significantly different between the high vs low Oncotype DX risk groups (P machine classifier trained to separate low/high Oncotype DX risk categories using the mitotic count determined by the DL classifier yielded a 83.19% classification accuracy. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  3. Early steps of adventitious rooting: morphology, hormonal profiling and carbohydrate turnover in carnation stem cuttings.

    Science.gov (United States)

    Agulló-Antón, María Ángeles; Ferrández-Ayela, Almudena; Fernández-García, Nieves; Nicolás, Carlos; Albacete, Alfonso; Pérez-Alfocea, Francisco; Sánchez-Bravo, José; Pérez-Pérez, José Manuel; Acosta, Manuel

    2014-03-01

    The rooting of stem cuttings is a common vegetative propagation practice in many ornamental species. A detailed analysis of the morphological changes occurring in the basal region of cultivated carnation cuttings during the early stages of adventitious rooting was carried out and the physiological modifications induced by exogenous auxin application were studied. To this end, the endogenous concentrations of five major classes of plant hormones [auxin, cytokinin (CK), abscisic acid, salicylic acid (SA) and jasmonic acid] and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid were analyzed at the base of stem cuttings and at different stages of adventitious root formation. We found that the stimulus triggering the initiation of adventitious root formation occurred during the first hours after their excision from the donor plant, due to the breakdown of the vascular continuum that induces auxin accumulation near the wounding. Although this stimulus was independent of exogenously applied auxin, it was observed that the auxin treatment accelerated cell division in the cambium and increased the sucrolytic activities at the base of the stem, both of which contributed to the establishment of the new root primordia at the stem base. Further, several genes involved in auxin transport were upregulated in the stem base either with or without auxin application, while endogenous CK and SA concentrations were specially affected by exogenous auxin application. Taken together our results indicate significant crosstalk between auxin levels, stress hormone homeostasis and sugar availability in the base of the stem cuttings in carnation during the initial steps of adventitious rooting. © 2013 Scandinavian Plant Physiology Society.

  4. Early histological, hormonal, and molecular changes during pineapple (Ananas comosus (L.) Merrill) artificial flowering induction.

    Science.gov (United States)

    Espinosa, Maita Eulalia Ávila; Moreira, Rafael Oliveira; Lima, André Almeida; Ságio, Solange Aparecida; Barreto, Horllys Gomes; Luiz, Sara Lazara Pérez; Abreu, Carlos Eduardo Aragón; Yanes-Paz, Ermis; Ruíz, Yanelis Capdesuñer; González-Olmedo, Justo Lorenzo; Chalfun-Júnior, Antonio

    2017-02-01

    Natural flowering can cause serious scheduling problems in the pineapple (Ananas comosus) industry and increase harvest costs. Pineapple flowering is thought to be triggered by increased ethylene levels and artificial forcing of pineapple flowering is a common practice to promote flowering synchronisation. However, little is known about the early hormonal and molecular changes of pineapple flowering induction and development. Here, we aimed to analyse the molecular, hormonal, and histological changes during artificial pineapple flowering by Ethrel ® 48 treatment. Histological analyses of the shoot apical meristem, leaf gibberellic acid (GA 3 ), and ethylene quantification were carried out during the first 72h after Ethrel ® 48 treatment. Expression profiles from ethylene biosynthesis (AcACS2 and AcACO1), gibberellin metabolism (AcGA2-ox1 and AcDELLA1), and flower development (FT-like gene (AcFT), LFY-like gene (AcLFY), and a PISTILLATA-like gene (AcPI)) genes were analysed during the first 24h after Ethrel ® 48 treatment. Differentiation processes of the shoot apical meristem into flower buds were already present in the first 72h after Ethrel ® 48 treatment. Ethrel ® 48 lead to a reduction in GA 3 levels, probably triggered by elevated ethylene levels and the positive regulation AcGA2-ox1. AcLFY activation upon Ethrel ® 48 may also have contributed to the reduction of GA 3 levels and, along with the up-regulation of AcPI, are probably associated with the flower induction activation. AcFT and AcDELLA1 do not seem to be regulated by GA 3 and ethylene. Decreased GA 3 and increased ethylene levels suggest an accumulation of AcDELLA1, which may display an important role in pineapple flowering induction. Thus, this study shows that molecular, hormonal, and histological changes are present right after Ethrel ® 48 treatment, providing new insights into how pineapple flowering occurs under natural conditions. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

    Directory of Open Access Journals (Sweden)

    Lap Ah Tse

    Full Text Available The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+ type.Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated.Altogether 52 (6.96% breast cancer cases and 23 (2.95% controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR of 2.41 (95%CI: 1.45-4.02. An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28, with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79 than an affected sister (OR = 2.06, 95%CI: 1.07-3.97, while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives.This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

  6. Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

    Science.gov (United States)

    Tse, Lap Ah; Li, Mengjie; Chan, Wing-cheong; Kwok, Chi-hei; Leung, Siu-lan; Wu, Cherry; Yu, Ignatius Tak-sun; Yu, Wai-cho; Lao, Xiangqian; Wang, Xiaorong; Wong, Carmen Ka-man; Lee, Priscilla Ming-yi; Wang, Feng; Yang, Xiaohong Rose

    2015-01-01

    The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+) type. Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings) were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age) and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated. Altogether 52 (6.96%) breast cancer cases and 23 (2.95%) controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR) of 2.41 (95%CI: 1.45-4.02). An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28), with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79) than an affected sister (OR = 2.06, 95%CI: 1.07-3.97), while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives. This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

  7. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Boér K

    2016-10-01

    Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

  8. Endocrine therapy use among elderly hormone receptor-pos...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators or aromatase...

  9. Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event

    Directory of Open Access Journals (Sweden)

    Karen A. Willoughby

    2014-07-01

    Full Text Available Autobiographical memory (AM is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO exposed during gestation to insufficient maternal thyroid hormone (TH, a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH, who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.

  10. Bovine serum prolactin, growth hormone, and triiodothyronine levels during late pregnancy and early lactation

    International Nuclear Information System (INIS)

    Johke, Tetsu; Hodate, Kouichi

    1977-01-01

    Changes of serum prolactin (PRL), growth hormone (GH), and triiodothyronine (T3) levels in Holstein dairy cows during late pregnancy and early lactation were determined by radioimmunoassays. The cows calved in September. Mean serum PRL ranged 9.9 ng/ml to 12.4 ng/ml during the 3rd to 7th day prepartum. It increased to a peak value of 87.3 ng/ml on the day of parturition from 57.5 ng/ml on the day before calving, and decreased to 13.9 ng/ml within 3 days postpartum. During the 2nd to 30th day prepartum, serum GH varied between 2.4 and 4.0 ng/ml and increased to 8.0 ng/ml on the day of calving. During a week postpartum, serum GH ranged from 5.2 to 8.2 ng/ml. Mean serum GH during a week postpartum was higher than that of prepartum (P < 0.001). Mean serum T3 level during 5 days prepartum varied 104.2 to 108.8 ng/dl and decreased to 93 ng/dl on the day of calving. During 5 days postpartum, mean T3 level varied 73.0 to 83.8 ng/dl. Contrary to GH, mean serum T3 level during 5 day postpartum was significantly lower than that of prepartum (P < 0.001). (auth.)

  11. Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma

    International Nuclear Information System (INIS)

    Pirnat, E.; Fidler, V.; Zaletel, K.; Gaberscek, S.; Hojker, S.

    2002-01-01

    Aim: In spite of extensive use of 131 I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131 I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq 131 I. Serum concentration of thyrotropin (TSH), free thyroxine (fT 4 ), free triiodothyronine (fT 3 ), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131 I. Results: After application of 131 I no clinical worsening was observed. FT 4 and fT 3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p 131 I induced necrosis of thyroid cells was found. Therefore, the application of 131 I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma. (orig.)

  12. Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis.

    Science.gov (United States)

    De Sousa, Sunita M C; Sheriff, Nisa; Tran, Chau H; Menzies, Alexander M; Tsang, Venessa H M; Long, Georgina V; Tonks, Katherine T T

    2018-06-01

    Hypophysitis develops in up to 19% of melanoma patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may avert life-threatening hypopituitarism. We aimed to assess the incidence of ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre, and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring could predict IH onset. We performed a retrospective cohort study of ipilimumab-treated patients at a quaternary melanoma referral centre in Australia. The inclusion criteria were patients with metastatic or unresectable melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements prior to ≥ 2 infusions. The main outcomes were IH incidence and TSH and cortisol patterns in patients who did and did not develop IH. Of 78 ipilimumab-treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a median duration of 13.0 weeks (range 7.7-18.1) following ipilimumab initiation. All patients whose TSH fell ≥ 80% compared to baseline developed IH, and, in 5/9 patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4 TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P = 0.006). TSH fall was detected at a median time of 9.2 (range 7.7-16.4) weeks after commencing ipilimumab, and a median of 3.6 (range of - 1.4 to 9.7) weeks before IH diagnosis. There was no difference in TSH between the groups before cycles 1-3 or in cortisol before cycles 1-4. TSH fall ≥ 80% may be an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an inexpensive tool to expedite IH diagnosis.

  13. The hormonal control of begging and early aggressive behavior : Experiments in black-headed gull chicks

    NARCIS (Netherlands)

    Groothuis, TGG; Ros, AFH; Groothuis, Ton G.G.

    The hormonal control of begging and sibling competition is largely unknown, but recent evidence suggests a role for steroid hormones. We tested the influence of the aromatizable androgen testosterone (T), the non-aromatizable androgen 5 alpha-dihydrotestosterone (DHT), and 17 beta-estradiol (E) on

  14. Thyroid stimulating hormone levels in newborns and early life exposure to endocrine disrupting chemicals - analysis of three European mother-child cohorts

    NARCIS (Netherlands)

    de Cock, Marijke; de Boer, Michiel R; Govarts, Eva; Iszatt, Nina; Palkovicova, Lubica; Lamoree, Marja H; Schoeters, Greet; Eggesbø, Merete; Trnovec, Tomas; Legler, Juliette; van de Bor, Margot

    2017-01-01

    BACKGROUND: Various studies report interactions between thyroid hormones and early life chemical exposure. Our objective was to analyse associations between markers of endocrine disrupting chemical exposure and thyroid function in newborns, determined in heel prick blood spots. METHODS: Three

  15. Investigations of hormones during early abortion induced by prostaglandin Fsub(2α) and 15(S)-methyl-PGFsub(2α)

    International Nuclear Information System (INIS)

    Seifert, B.; Liedtke, M.P.; Brockmann, J.; Beissert, M.; Gstoettner, H.; Alexander, H.; Herter, U.

    1978-01-01

    In early pregnancy up the 7th week of pregnancy PGFsub(2α) was infused and 15(S)-methyl-PGFsub(2α) was applied i.m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGFsub(2α) is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGFsub(2α) produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnangy. (author)

  16. Early-life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

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    Tomoko eSoga

    2015-11-01

    Full Text Available Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinising hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP-tagged GnIH-transgenic rats. Socially isolated rats were observed for anxious and depressive behaviours. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group -housing. We also inspected serotonergic fibre juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviours. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fibre juxtapositions on EGFP–GnIH neurons was also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  17. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

    Science.gov (United States)

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  18. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    2017-04-18

    Apr 18, 2017 ... significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic ... types characterized by a particularly poor prognosis (Aceto et al. ... Progesterone receptor status. PRlow. 70. 76.9. PRhigh. 21. 23.1. NA .... (M<88.82 pg/mg) had lower percentage of relapses and.

  19. Early change of thyroid hormone concentration after {sup 131}I treatment in patients with solitary toxic adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Pirnat, E.; Fidler, V.; Zaletel, K.; Gaberscek, S.; Hojker, S. [Univ. Medical Centre Ljubljana, Dept. of Nuclear Medicine (Slovenia)

    2002-08-01

    Aim: In spite of extensive use of {sup 131}I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether {sup 131}I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq {sup 131}I. Serum concentration of thyrotropin (TSH), free thyroxine (fT{sub 4}), free triiodothyronine (fT{sub 3}), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of {sup 131}I. Results: After application of {sup 131}I no clinical worsening was observed. FT{sub 4} and fT{sub 3} concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p<0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. Conclusion: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by {sup 131}I induced necrosis of thyroid cells was found. Therefore, the application of {sup 131}I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma. (orig.)

  20. Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer

    Directory of Open Access Journals (Sweden)

    Buechler Steven

    2009-07-01

    Full Text Available Abstract Background Many breast cancer patients remain free of distant metastasis even without adjuvant chemotherapy. While standard histopathological tests fail to identify these good prognosis patients with adequate precision, analyses of gene expression patterns in primary tumors have resulted in more successful diagnostic tests. These tests use continuous measurements of the mRNA concentrations of numerous genes to determine a risk of metastasis in lymph node negative breast cancer patients with other clinical traits. Methods A survival model is constructed from genes that are both connected with relapse and have expression patterns that define distinct subtypes, suggestive of different cellular states. This in silico study uses publicly available microarray databases generated with Affymetrix GeneChip technology. The genes in our model, as represented by array probes, have distinctive distributions in a patient cohort, consisting of a large normal component of low expression values; and a long right tail of high expression values. The cutoff between low and high expression of a probe is determined from the distribution using the theory of mixture models. The good prognosis group in our model consists of the samples in the low expression component of multiple genes. Results Here, we define a novel test for risk of metastasis in estrogen receptor positive (ER+ breast cancer patients, using four probes that determine distinct subtypes. The good prognosis group in this test, denoted AP4-, consists of the samples with low expression of each of the four probes. Two probes target MKI67, antigen identified by monoclonal antibody Ki-67, one targets CDC6, cell division cycle 6 homolog (S. cerevisiae, and a fourth targets SPAG5, sperm associated antigen 5. The long-term metastasis-free survival probability for samples in AP4- is sufficiently high to render chemotherapy of questionable benefit. Conclusion A breast cancer subtype defined by low

  1. Growth hormone and prolactin radioimmunoassay in early diagnosis of pituitary tumors

    International Nuclear Information System (INIS)

    Gembicki, M.; Kosowicz, J.

    1978-01-01

    Results of prolactin and HGH determination in basal conditions and following stimulation tests in the group of 68 patients with pituitary or suprasellar tumors are presented. In acromegaly elevated level of HGH in fasting state, lack of supression after glucose loading and parodoxical drop of HGH after L-dopa administration were observed. In pituitary tumors without acromegaly determinations of HGH during insulin induced hypoglycemia revealed lack of HGH response to such stimulation in 25 cases which indicated hypopituitarism. In 10 cases elevated prolactin levels (48 - 1000 ng/ml) were observed, this indicates that some of so-called inactive tumors are in fact hormonally active. (author)

  2. Possible effects of an early diagnosis and treatment in patients with growth hormone deficiency: the state of art.

    Science.gov (United States)

    Stagi, Stefano; Scalini, Perla; Farello, Giovanni; Verrotti, Alberto

    2017-09-16

    Growth hormone deficiency (GHD) is a relatively uncommon and heterogeneous endocrine disorder presenting in childhood with short stature. However, during the neonatal period, the metabolic effects of GHD may to require prompt replacement therapy to avoid possible life-threatening complications. An increasing amount of data suggests the importance of an early diagnosis and treatment of GHD because of its auxological, metabolic, and neurodevelopmental features with respect to the patients diagnosed and treated later in life.The available results show favourable auxological outcomes for patients with GHD diagnosed and treated with r-hGH early in life compared with those from patients with GHD who do not receive this early diagnosis and treatment. Because delayed referral for GHD diagnosis and treatment is still frequent, these results highlight the need for more attention in the diagnosis and treatment of GHD.Despite these very encouraging data regarding metabolic and neurodevelopmental features, further studies are needed to better characterize these findings. Overall, the importance of early diagnosis and treatment of GHD needs to be addressed.

  3. Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

    International Nuclear Information System (INIS)

    Barni, S.; Lissoni, P.; Tancini, G.

    1986-01-01

    While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

  4. Correlation between pregnancy outcomes and hormone levels in early pregnancy of women with threatened abortion and subchorionic hematoma

    Directory of Open Access Journals (Sweden)

    Xiao-Hua Liu

    2016-02-01

    Full Text Available Objective: To investigate the correlation between pregnancy outcomes and hormone levels in early pregnancy of women with threatened abortion and subchorionic hematoma. Methods: Three groups of subjects (48 cases each were selected including the group of healthy pregnant women (Group C, and the two groups of subchorionic hematoma diagnosed via B-ultrasound examination with and without (Groups A and B positive symptoms of threatened abortion such as abdominal pain, colporrhagia etc. Chemiluminescence analysis was applied to determine serum progesterone and HCG levels of all three groups, and investigate the correlation between variations of such levels and pregnancy outcomes. Results: Statistical significance existed in the differences between serum progesterone and HCG levels of the three groups at 12, 28 and 37 weeks of gestation. In early pregnancy, serum progesterone and β-HCG levels were lower in Group A than Groups B and C, and lower in Group B than Group C. In the second trimester, the serum β-HCG level was higher, while the progesterone level lower in Group A than Groups B and C; the serum β-HCG level higher, while the progesterone level lower in Group B than Group C. And the comparative results in late pregnancy were the same as those of the second trimester. The premature birth rate, abortion rate, fetal death rate were the highest, and the full time delivery rate was the lowest in Group A among all the three groups. Adverse pregnancy outcomes of women with threatened abortion and subchorionic hematoma were closely related to serum progesterone and HCG levels in early gestation. Conclusion: Serum progesterone and HCG levels in early pregnancy of women with threatened abortion and subchorionic hematoma are positively correlated with pregnancy outcomes; the lower such levels of the two early indicators, the higher the incidence of adverse pregnancy outcomes. Therefore, tests of early pregnancy serum progesterone and HCG levels can be

  5. Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jin

    2012-07-01

    Full Text Available Prader-Willi syndrome (PWS is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR, gamete complementation (GC, monosomy rescue (MR, and postfertilization mitotic nondisjunction (Mit. Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.

  6. Tight interplay in early pregnancy between follistatin and anti-mullerian hormone in women with polycystic ovarian syndrome (PCOS).

    Science.gov (United States)

    Köninger, Angela; Kampmeier, Antje; Mach, Pawel; Schmidt, Boerge; Strowitzki, Thomas; Kimmig, Rainer; Gellhaus, Alexandra

    2018-05-01

    Follistatin levels increase during the course of pregnancy and may play a role in ovarian arrest, reflected by the simultaneous decrease of anti-mullerian-hormone (AMH) levels. The aim of the study was to investigate AMH and follistatin levels during the hormonal window at the beginning of pregnancy. Since both parameters are described as deregulated in polycystic ovarian syndrome (PCOS), subgroup analysis of PCOS patients may additionally elucidate their interplay and effects on ovarian activity. Serum samples were retrospectively analyzed using the AMH Gen II ELISA and the Human Follistatin Quantikine ELISA Kit. Samples were collected longitudinally from 57 patients (32 with PCOS and 25 controls) before conception and during the first trimester. In 18 patients, measurements from the early and the late first trimester were available. Potential associations of AMH and follistatin levels with PCOS-related parameters were compared between the subgroups as well as longitudinally before and in the first trimester of pregnancy. For statistical analysis, the Spearman's correlation, Wilcoxon test, t test, Friedman test and multiple linear regression analysis was performed. In contrast to AMH, follistatin levels differed not between controls and PCOS patients before and in pregnancy. In both subgroups, AMH levels significantly decreased and follistatin levels significantly increased in longitudinally performed measurements before conceiving and in the first trimester of pregnancy. Follistatin levels are not suited as a biomarker for PCOS, but could be involved in suppressing ovarian activity, as reflected by AMH levels at the beginning of pregnancy.

  7. Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.

    Science.gov (United States)

    Nelson, Anita L

    2015-01-01

    As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma. This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs. Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.

  8. Growth hormone treatment for childhood short stature and risk of stroke in early adulthood.

    Science.gov (United States)

    Poidvin, Amélie; Touzé, Emmanuel; Ecosse, Emmanuel; Landier, Fabienne; Béjot, Yannick; Giroud, Maurice; Rothwell, Peter M; Carel, Jean-Claude; Coste, Joël

    2014-08-26

    We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood. Adult morbidity data were obtained in 2008-2010 for 6,874 children with idiopathic isolated GH deficiency or short stature who started GH treatment between 1985 and 1996. Cerebrovascular events were validated using medical reports and imaging data and classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. Case ascertainment completeness was estimated with capture-recapture methods. The incidence of stroke and of stroke subtypes was calculated and compared with population values extracted from registries in Dijon and Oxford, between 2000 and 2012. Using both Dijon and Oxford population-based registries as references, there was a significantly higher risk of stroke among patients treated with GH in childhood. The excess risk of stroke was mainly attributable to a very substantially and significantly higher risk of hemorrhagic stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry rates considered, and accounting or not accounting for missed cases), and particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to 9.3). We report a strong relationship between hemorrhagic stroke and GH treatment in childhood for isolated growth hormone deficiency or childhood short stature. Patients treated with GH worldwide should be advised about this association and further studies should evaluate the potentially causal role of GH treatment in these findings. © 2014 American Academy of Neurology.

  9. Dynamically observing the value of the changes of serum sex hormone levels of early pregnancy after drug-induced abortion

    International Nuclear Information System (INIS)

    Zhao Honggang; Dong Hua; Gu Yan; Zhang Zuncheng

    2009-01-01

    Objective: To observe the value of the changes of serum β-human chorionic gonadotropin (β-HCG), estradiol (E), progesterone (P) Levels of early pregnancy after drug-induced abortion dynamically. Methods: Assessing 55 women proved pregnant by urine or blood HCG retrospecticly, who had terminated their pregnancy by mifepristonr and misoprostol. Meanwhile the serum levels of β-HCG, E, P were monitored dynamically. Results: Among the 55 patients, the levels of β-HCG, E and P had significant decreased (t β-HCG =4.845, t E =7.655, t P =11.390, P E =9.089, P P =2.910, P<0.05). Conclusion: Detectint the serum hormone's levels after drug-induced abortion by chemiluminescent immunoassay, we can assess indirectly the value of administration of mifepristone and misoprostol, predict the prolonged vaginal bleeding after drug-induced abortion, and the outcome of the treatment, which determine wether need another curestage. (authors)

  10. A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

    Science.gov (United States)

    Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

    2015-04-01

    Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

  11. Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

    Science.gov (United States)

    Carrasquilla, Germán D; Berglund, Anita; Gigante, Bruna; Landgren, Britt-Marie; de Faire, Ulf; Hallqvist, Johan; Leander, Karin

    2015-06-01

    This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

  12. Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

    Science.gov (United States)

    Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

    2012-04-01

    Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (ppenis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.

  13. Experimental peptide receptor radionuclide therapy in radioiodine negative somatostatin receptor positive thyroid cancer

    International Nuclear Information System (INIS)

    Nilica, B.; Kroiss, A.; Putzer, D.; Uprimmy, C.; Warwitz, B.; Kendler, D.; Waitz, D.; Virgolini, I.

    2015-01-01

    Full text of publication follows. Purpose: This retrospective analysis evaluated the time to progression (TTP), progression free survival (PFS) and overall survival (OS) in patients with radioiodine negative thyroid cancer who had undergone peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTA-TATE, 177 Lu-DOTA-LAN, 90 Y-DOTA-TOC or 90 Y-DOTA-LAN after tumor progression. Methods: Data derived from twenty patients with either differentiated (n=15), anaplastic (n=1) or medullary (n=4) somatostatin receptor positive thyroid cancer who had received treatment with PRRT after tumor progression. TTP, PFS and OS were defined according to the clinical trial endpoints suggested by the FDA (Food and Drug Administration). Progressive disease was defined by sonography, FDG-PET, Ga-DOTA-TOC-PET, or CT (RECIST Criteria). Results: In 17 patients the median overall survival time after the first PRRT was 17.3 (range: 0.1 - 109.7) months. Three patients still alive are actually showing stable disease. The median of PFS in 20 Patients (6 with more than one PRRT-cycle or PRRT-substance) has been 10.9 (range: 0.1 - 44.0) months. The median TTP was 15.6 (range 4.4 to 29.2) months. Conclusion: PRRT appears to be useful in patients with somatostatin receptor positive but radioiodine negative thyroid cancer as a complementary palliative cytotoxic therapy. (authors)

  14. Radionuclide bone scintigraphy in early detection of avascular osteonecrosis occurred in recovered SARS patients after hormone therapy

    International Nuclear Information System (INIS)

    Wang Qian; Huang Lili; Qin Shuling; Wang Yu; Nie Yuxin; Liang Tiejun; Zhang Caiqun; Zhao Yamei

    2005-01-01

    Objective: To analyze the characteristics of bone scintigraphy in patients who recovered from the severe acute respiratory syndrome (SARS), and to evaluate the clinical value of bone scintigraphy in the early diagnosis of avascular osteonecrosis (AVN) after hormone therapy. Methods: Bone scintigraphy was performed in 66 SARS patients. Among them 54 underwent MRI in bilateral hips and knees. Both images were compared and followed up clinically. Results: Abnormal scintigraphy was found in 30 (45.5%) of the 66 recovered SARS patients. Total 82 foci were found in hip, knee, ankle, elbow, shoulder, wrist and the middle of the tibia. Hip and knee joints were the most involved sites. 25 patients with 71 lesions were symptomatic, whereas 11 in 5 patients were asymptomatic, lesions in 8 patients were multifocal. The lesions found in scintigraphy and MRI were concordant in 92.6% of the joints. But more lesions could be detected by bone scintigraphy. Conclusions: SARS patients have a high occurrence of AVN, usually involved in multiple sites. Bone scintigraphy should be the first choice method used for early detection of AVN. (authors)

  15. Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice.

    Science.gov (United States)

    Ahlkvist, L; Vikman, J; Pacini, G; Ahrén, B

    2012-10-10

    Apart from glucose, proteins and lipids also stimulate incretin and islet hormone secretion. However, the glucoregulatory effect of macronutrients in combination is poorly understood. We therefore developed an oral mixed meal model in mice to 1) explore the glucagon-like peptide-1 (GLP-1) and islet hormone responses to mixed meal versus isocaloric glucose, and 2) characterize the relative contribution of individual macronutrients to these responses. Anesthetized C57BL/6J female mice were orally gavaged with 1) a mixed meal (0.285 kcal; glucose, whey protein and peanut oil; 60/20/20% kcal) versus an isocaloric glucose load (0.285 kcal), and 2) a mixed meal (0.285 kcal) versus glucose, whey protein or peanut oil administered individually in their mixed meal caloric quantity, i.e., 0.171, 0.055 and 0.055 kcal, respectively. Plasma was analyzed for glucose, insulin and intact GLP-1 before and during oral challenges. Plasma glucose was lower after mixed meal versus after isocaloric glucose ingestion. In spite of this, the peak insulin response (P=0.02), the peak intact GLP-1 levels (P=0.006) and the estimated β-cell function (P=0.005) were higher. Furthermore, the peak insulin (P=0.004) and intact GLP-1 (P=0.006) levels were higher after mixed meal ingestion than the sum of responses to individual macronutrients. Compared to glucose alone, we conclude that there is a marked early insulin response to mixed meal ingestion, which emanates from a synergistic, rather than an additive, effect of the individual macronutrients in the mixed meal and is in part likely caused by increased levels of GLP-1. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Clinical features and hormonal profiles of cloprostenol-induced early abortions in heifers monitored by ultrasonography

    Directory of Open Access Journals (Sweden)

    Beckers Jean-François

    2006-11-01

    Full Text Available Abstract Background The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1, the main metabolite of prostaglandin F2α (PG metabolite and progesterone (P4 in heifers in which early abortions were induced. Methods Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite. Results The foetal heartbeat rates varied from 170–186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4 – 40.0 ng/mL, 158 – 275 pmol/L and 20.7 – 46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8 – 6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection. Conclusion The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy.

  17. Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.

    Science.gov (United States)

    Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G; Zuk, Samantha M; Lowe, Val J; Fields, Julie A; Gunter, Jeffrey L; Senjem, Matthew L; Settell, Megan L; Gleason, Carey E; Shuster, Lynne T; Bailey, Kent R; Dowling, N Maritza; Asthana, Sanjay; Jack, Clifford R; Rocca, Walter A; Miller, Virginia M

    2018-04-17

    The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health. Participants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68). Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo. The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT. Copyright © 2018 The

  18. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

    Science.gov (United States)

    Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

    2009-07-01

    PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

  19. Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

    Energy Technology Data Exchange (ETDEWEB)

    Mendizabal, A.F.; Quiroga, S.; Farinati, Z.; Lahoz, M.; Nagle, C.

    1984-11-01

    The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E/sub 3/G) and pregnanediol-3-glucuronide (P/sub 2/G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E/sub 3/G and P/sub 2/G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E/sub 3/G and P/sub 2/G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit.

  20. Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

    International Nuclear Information System (INIS)

    Mendizabal, A.F.; Quiroga, S.; Farinati, Z.; Lahoz, M.; Nagle, C.

    1984-01-01

    The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E 3 G) and pregnanediol-3-glucuronide (P 2 G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E 3 G and P 2 G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E 3 G and P 2 G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit

  1. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

    Science.gov (United States)

    Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

    1999-02-01

    Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and

  2. Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

    Science.gov (United States)

    Ma, W; Zhang, T-F; Lu, P; Lu, S H

    2014-01-01

    Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

  3. Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone Receptor Status: A Cost-Utility Analysis.

    Science.gov (United States)

    Leung, William; Kvizhinadze, Giorgi; Nair, Nisha; Blakely, Tony

    2016-08-01

    The anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone receptor (PR) status, which has previously been unexplored, to assist prioritisation. A cost-utility analysis was performed using a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo regimen of trastuzumab with chemotherapy alone using the latest (2014) effectiveness measures from landmark randomised trials. A New Zealand (NZ) health system perspective was adopted, employing high-quality national administrative data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29-2.37) for the worst prognosis (ER-/PR-) subtype compared to the best prognosis (ER+/PR+) subtype, causing incremental cost-effectiveness ratios (ICERs) for the former to be less than half those of the latter for the age groups from 25-29 to 90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45). If we were to strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross domestic product per capita (2011 purchasing power parity [PPP]-adjusted: US$30,300; €23,700; £21,200), our study suggests that trastuzumab (2011 PPP-adjusted US$45,400/€35,900/£21,900 for 1 y at formulary prices) may not be cost-effective for ER+ (which are 61% of all) node-positive HER2+ early breast cancer patients but cost-effective for ER-/PR- subtypes (37% of all cases) to age 69 y. Market entry of trastuzumab biosimilars will likely reduce the ICER to below this threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer. Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had the same result. A key limitation was a lack of treatment

  4. Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone Receptor Status: A Cost-Utility Analysis.

    Directory of Open Access Journals (Sweden)

    William Leung

    2016-08-01

    Full Text Available The anti-human epidermal growth factor receptor 2 (HER2 monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER and progesterone receptor (PR status, which has previously been unexplored, to assist prioritisation.A cost-utility analysis was performed using a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo regimen of trastuzumab with chemotherapy alone using the latest (2014 effectiveness measures from landmark randomised trials. A New Zealand (NZ health system perspective was adopted, employing high-quality national administrative data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29-2.37 for the worst prognosis (ER-/PR- subtype compared to the best prognosis (ER+/PR+ subtype, causing incremental cost-effectiveness ratios (ICERs for the former to be less than half those of the latter for the age groups from 25-29 to 90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45. If we were to strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross domestic product per capita (2011 purchasing power parity [PPP]-adjusted: US$30,300; €23,700; £21,200, our study suggests that trastuzumab (2011 PPP-adjusted US$45,400/€35,900/£21,900 for 1 y at formulary prices may not be cost-effective for ER+ (which are 61% of all node-positive HER2+ early breast cancer patients but cost-effective for ER-/PR- subtypes (37% of all cases to age 69 y. Market entry of trastuzumab biosimilars will likely reduce the ICER to below this threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer. Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had the same result. A key limitation was a lack of

  5. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  6. Parathyroid Hormone (1-34 Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

    Directory of Open Access Journals (Sweden)

    Jisun Huh

    2017-01-01

    Full Text Available Purpose. This study evaluated the effect of administering intermittent parathyroid hormone [PTH (1-34, henceforth PTH] on the early-stage bone healing of maxillary sinus augmentation in healthy rabbits. Materials and Methods. Bovine bone mineral was grafted on the sinuses of 20 female New Zealand white rabbits. The animals were randomly divided into two groups, PTH (n=10 or saline (n=10, in which either PTH or saline was injected subcutaneously 5 days a week for 2 weeks. Half of the animals in each group were killed at 2 weeks postoperatively and the other half were killed at 4 weeks postoperatively. The dosage of PTH was 10 μg/kg/day. Radiographic and histomorphometric analyses were performed. Result. The new bone area (NBA did not differ significantly between the PTH and saline groups. The NBA in the PTH group in the total augmented area and in the demarcated window, center, and Schneiderian membrane regions increased significantly from 2 to 4 weeks. The number of osteoclasts decreased significantly from 2 to 4 weeks in both groups, with no difference between the two groups. Conclusion. Intermittent PTH might not stimulate new bone formation in healthy rabbits during the first 4 weeks of healing.

  7. Delayed administration of recombinant human parathyroid hormone improves early biomechanical strength in a rat rotator cuff repair model.

    Science.gov (United States)

    Duchman, Kyle R; Goetz, Jessica E; Uribe, Bastian U; Amendola, Andrew M; Barber, Joshua A; Malandra, Allison E; Fredericks, Douglas C; Hettrich, Carolyn M

    2016-08-01

    Despite advances in intraoperative techniques, rotator cuff repairs frequently do not heal. Recombinant human parathyroid hormone (rhPTH) has been shown to improve healing at the tendon-to-bone interface in an established acute rat rotator cuff repair model. We hypothesized that administration of rhPTH beginning on postoperative day 7 would result in improved early load to failure after acute rotator cuff repair in an established rat model. Acute rotator cuff repairs were performed in 108 male Sprague-Dawley rats. Fifty-four rats received daily injections of rhPTH beginning on postoperative day 7 until euthanasia or a maximum of 12 weeks postoperatively. The remaining 54 rats received no injections and served as the control group. Animals were euthanized at 2 and 16 weeks postoperatively and evaluated by gross inspection, biomechanical testing, and histologic analysis. At 2 weeks postoperatively, rats treated with rhPTH demonstrated significantly higher load to failure than controls (10.9 vs. 5.2 N; P = .003). No difference in load to failure was found between the 2 groups at 16 weeks postoperatively, although control repairs more frequently failed at the tendon-to-bone interface (45.5% vs. 22.7%; P = .111). Blood vessel density appeared equivalent between the 2 groups at both time points, but increased intracellular and extracellular vascular endothelial growth factor expression was noted in the rhPTH-treated group at 2 weeks. Delayed daily administration of rhPTH resulted in increased early load to failure and equivalent blood vessel density in an acute rotator cuff repair model. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  8. A Comparison of the Hormonal Profile of Early Androgenetic Alopecia in Men With the Phenotypic Equivalent of Polycystic Ovarian Syndrome in Women.

    Science.gov (United States)

    Sanke, Sarita; Chander, Ram; Jain, Anju; Garg, Taru; Yadav, Pravesh

    2016-09-01

    Early androgenetic alopecia (AGA) is patterned hair loss occurring before age 30 years. Early AGA in men is frequently reported as the phenotypic equivalent of polycystic ovarian syndrome (PCOS) in women, which carries the risk of developing obesity, metabolic syndrome, and cardiovascular diseases. Very few studies have been conducted to evaluate this. To study the hormonal profile of men with early AGA and to evaluate if early AGA in men can be considered as the phenotypic equivalent of PCOS, the associated risks of which are well known. This case-control study was conducted from January 1, 2014, to March 31, 2015, in a tertiary care government hospital. Fifty-seven men aged 19 to 30 years presenting with patterned hair loss were recruited as study participants. Thirty-two age-matched men with no evidence of hair loss were recruited as controls. Men who had any established endocrine disorder, diabetes mellitus, or cardiovascular disease and those who took any oral medication or hormonal treatment for hair loss were excluded from the study. The serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, fasting plasma glucose, and insulin levels were measured. Insulin resistance (IR) and free androgen index (FAI) were calculated and compared with age- and sex-matched controls. The primary outcome was to measure the clinico-endocrinological profiles (LH, FSH, SHBG, DHEAS, and testosterone levels) of men with early AGA and to compare it with the PCOS profile; the secondary outcome was to establish a relationship between this endocrinological profile and IR. Compared with the 32 controls, the 57 participants with AGA showed significantly increased mean (SD) levels of testosterone (24.61 [7.97] vs 20.57 [4.9] nmol/L; P = .04), DHEAS (3.63 [2.19] vs 2.64 [1.49] µg/mL; P = .02), LH (7.78 [3.19] vs 4.56 [2.01] mIU/mL; P PCOS. The

  9. Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

    Science.gov (United States)

    Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

    2018-03-01

    The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

  10. Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

    OpenAIRE

    Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

    2012-01-01

    Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin?) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean d...

  11. The early changes of thyroid hormone concentrations after 131I therapy for graves' hyperthyroidism - the role of pretreatment with methimazole

    International Nuclear Information System (INIS)

    Pirnat, E.; Fidler, V.; Zaletel, K.; Gaberscek, S.; Hojker, S.

    2002-01-01

    Full text: 131 I therapy may cause exacerbation of hyperthyroidism due to leakage of previously formed thyroid hormones from damaged thyroid cells in Graves' patients. To avoid this complication pretreatment with antithyroid drugs is recommended. Otherwise, the use of antithyroid drugs prior to 131 I therapy may diminish the success of 131 I therapy and should therefore be discontinued. The aim of our prospective clinical study was to compare early changes of thyroid hormone concentrations after 131 I therapy in Graves' patients, pretreated or not pretreated with methimazole. 92 consecutive Graves' patients, 84 females and 8 males, aged 17 to 80 were treated with 555 MBq of 131 I. Absorbed dose of 131 I was calculated. In the first group of 22 patients treatment with methimazole (20 mg/day) was discontinued 7 days before 131 I therapy, the second group of 33 patients received methimazole until the day of 131 I therapy and the third group of 37 patients was not pretreated with methimazole before 131 I therapy. 7 and 2 days before 131 I therapy and 2, 5, 12 and 30 days after serum free T 4 (fT 4 ) and free T 3 (fT 3 ) concentrations were measured. In the first group a significant increase of fT 4 and fT 3 was observed 7 days after discontinuation of methimazole (fT 4 14.60 ± 4.10 vs. 18.25 ± 7.16; fT 3 5.45 ± 1.44 vs. 7.79 ± 5.27 pmol/l), while gradual decrease of fT 4 and fT 3 was observed after 131 I therapy. In the second group a significant increase of fT 4 and fT 3 after 131 I therapy peaking on day 5 was observed (fT 4 20.91 ± 13.70 vs. 27.85 ± 18.17; fT 3 7.81 ± 5.21 vs. 9.42 ± 6.21 pmol/l). In the third group significant decrease of fT 4 and fT 3 concentrations was observed after 131 I therapy (fT 4 36.12 ± 18.55 vs. on day 12th 27.49 ± 15.20; fT 3 12.66 ± 7.04 vs. on day 12th 8.31 ± 4.92 pmol/l). No correlation between absorbed dose of 131 I and changes of fT 4 and fT 3 concentrations was observed. Therefore, our results indicate that not 131 I

  12. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Directory of Open Access Journals (Sweden)

    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  13. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

    Science.gov (United States)

    Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

    2013-06-15

    A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

  14. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    Science.gov (United States)

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  15. Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia.

    Science.gov (United States)

    O'Shea, T; Crowley, R K; Farrell, M; MacNally, S; Govender, P; Feeney, J; Gibney, J; Sherlock, M

    2016-01-01

    Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0-1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels.Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours.Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.

  16. Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

    Science.gov (United States)

    Holl, Katsiaryna; Lundin, Eva; Surcel, Heljä-Marja; Grankvist, Kjell; Koskela, Pentti; Dillner, Joakim; Hallmans, Göran; Wadell, Göran; Olafsdottir, Gudridur H; Ogmundsdottir, Helga M; Pukkala, Eero; Lehtinen, Matti; Stattin, Pär; Lukanova, Annekatrin

    2009-06-15

    According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Copyright 2008 UICC.

  17. Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer.

    Science.gov (United States)

    Shen, Tiansheng; Brandwein-Gensler, Margaret; Hameed, Omar; Siegal, Gene P; Wei, Shi

    2015-11-01

    Despite the controversies, estrogen receptor-negative/progesterone receptor-positive (ER-/PR+) breast cancers have a reported incidence of 1% to 4%. These tumors are less well defined, and it is unclear whether ER-/PR+ represents a distinct subtype. Thus, we analyzed 5374 consecutive breast cancers to characterize the clinicopathological features of this underrecognized subset of tumors. The ER-/PR+ tumors, constituting 2.3% of the total, were mostly high grade and significantly seen in younger patients and African American women when compared with the ER+/PR+ and ER+/PR- groups, but similar to that of ER-/PR- phenotype (P < .0001). A significantly prolonged relapse-free survival (RFS) was associated with the ER+/PR+ subtype when compared with the ER+/PR- (P = .0002) or ER-/PR+ (P = .0004) tumors, whereas all 3 groups showed a superior outcome to that of the ER-/PR- phenotype. In the subset of patients receiving endocrine therapy, those with ER+/PR+ tumors had a significantly prolonged RFS (P = .001) and disease-specific survival (P = .005) when compared with the group with an ER+/PR- phenotype, but did not significantly differ from those with ER-/PR+ tumors. No significant survival advantage was found between the ER+/PR- and ER-/PR+ tumors in any group of patients analyzed. Furthermore, a higher PR expression was associated with a favorable RFS and disease-specific survival in the patients with ER-/PR+ tumors. Therefore, the ER-/PR+ tumors demonstrate a similar, if not higher than, response rate to endocrine therapy when compared with the ER+/PR- tumors and thus are important to identify. Routine PR testing remains necessary in assisting clinical decision making in the pursuit of precision medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer – An AZURE (BIG 01/04 sub-study

    Directory of Open Access Journals (Sweden)

    Caroline Wilson

    2017-11-01

    Full Text Available Purpose: Adjuvant bisphosphonates have been shown to improve disease outcomes in early breast cancer in women who are postmenopausal at the start of treatment. We explored the influence of pretreatment serum levels of reproductive hormones in the hypothalamic-pituitary-gonadal (HPG axis from a subset of patients included in the AZURE trial to investigate their impact on disease recurrence and whether reproductive hormone measurements are of value in selecting patients for treatment with adjuvant zoledronic acid.Patients and methods; The AZURE trial is an academic, multi-centre, international phase III trial that randomised patients to standard adjuvant therapy (chemotherapy and/or endocrine therapy±intravenous zoledronic acid, 4 mg for 5 years. Serum from 865 patients taken at randomisation was stored at −80 °C prior to central batch analysis for inhibin A, oestradiol and follicle stimulating hormone (FSH. We assessed the clinical value of pretreatment hormone levels for predicting invasive disease free survival (IDFS, skeletal recurrence and distant recurrence and response to treatment with zoledronic acid. Results: Oestradiol in the postmenopausal range (26 IU/l was associated with a longer time to bone as first recurrence (HR 0.66 95%CI: 0.41–1.04 p=0.072 compared to an FSH ≤26 IU/l. When all 3 hormone levels were within the assay specified postmenopausal range, a trend to improved IDFS was seen with addition of zoledronic acid in biochemically postmenopausal women only (postmenopausal HR=0.81; 95%CI: 0.54–1.22, non-postmenopausal HR=0.99; 95%CI: 0.69–1.39 with risk reductions that mirrored the results of the main AZURE study, although the interaction between menopausal status and treatment effect was not statistically significant (p=0.47. Conclusion: Oestradiol and FSH may influence the pattern of disease recurrence with postmenopausal levels possibly creating a less conducive environment for the

  19. Hormone Stories in Argentina.Obesity in children and early diagnosis of pregnancy in the 1930s and 1940s

    Directory of Open Access Journals (Sweden)

    Cecilia Rustoyburu

    2015-09-01

    Full Text Available This article inquires, from a gender perspective, knowledge production about hormones in Argentina, between the years 1930-1940. We understand that a historical analysis of scientific ideas and clinical practices allows explore how they involved on the social scenario which they belong, plus the institutional contexts where they are elaborated. We will focus on endocrinologist's Hospital de Niños de Buenos Aires perspective about obesity on childhood, and adipose genital síndrome, andearly diagnosis of pregnancy and chorionic gonadotropin hormone in the 1930s and 1940s

  20. Early Hormonal Influences on Childhood Sex-Typed Activity and Playmate Preferences: Implications for the Development of Sexual Orientation.

    Science.gov (United States)

    Berenbaum, Sheri A.; Snyder, Elizabeth

    1995-01-01

    Examined hormonal influences on activity and playmate preferences in children with congenital adrenal hyperplasia (CAH) age 2.5 to 12 years and their relatives. Found that girls with CAH preferred boys' toys and activities, whereas boys with CAH did not differ significantly from controls. Activity and playmate preferences were not related. (MDM)

  1. Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

    Science.gov (United States)

    Takahashi, L K; Kalin, N H

    1991-08-30

    Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

  2. Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H

    1985-01-01

    A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth cur...... but is not a sufficiently clear marker to allow prediction of the endocrine sensitivity of individual breast tumours....

  3. Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer ?

    OpenAIRE

    O'Shaughnessy, J.; Campone, M.; Brain, E.; Neven, P.; Hayes, D.; Bondarenko, I.; Griffin, T. W.; Martin, J.; De Porre, P.; Kheoh, T.; Yu, M. K.; Peng, W.; Johnston, S.

    2015-01-01

    Background Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients a...

  4. Enhanced Striatal β1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats

    Science.gov (United States)

    Perry, Adam N.; Westenbroek, Christel; Hedges, Valerie L.; Becker, Jill B.; Mermelstein, Paul G.

    2013-01-01

    After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17β-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in β1-adrenergic receptor (β1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in β2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in β1AR expression when compared with gonadectomized males. No sex difference in β1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased β1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased β1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased β1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of β1AR action was eliminated with 17β-estradiol addition to the media, directly implicating this hormone as a regulator of β1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence. PMID:23533220

  5. Hormonal Signaling Cascade during an Early-Adult Critical Period Required for Courtship Memory Retention in Drosophila.

    Science.gov (United States)

    Lee, Sang Soo; Ding, Yike; Karapetians, Natalie; Rivera-Perez, Crisalejandra; Noriega, Fernando Gabriel; Adams, Michael E

    2017-09-25

    Formation and expression of memories are critical for context-dependent decision making. In Drosophila, a courting male rejected by a mated female subsequently courts less avidly when paired with a virgin female, a behavioral modification attributed to "courtship memory." Here we show the critical role of hormonal state for maintenance of courtship memory. Ecdysis-triggering hormone (ETH) is essential for courtship memory through regulation of juvenile hormone (JH) levels in adult males. Reduction of JH levels via silencing of ETH signaling genes impairs short-term courtship memory, a phenotype rescuable by the JH analog methoprene. JH-deficit-induced memory impairment involves rapid decay rather than failure of memory acquisition. A critical period governs memory performance during the first 3 days of adulthood. Using sex-peptide-expressing "pseudo-mated" trainers, we find that robust courtship memory elicited in the absence of aversive chemical mating cues also is dependent on ETH-JH signaling. Finally, we find that JH acts through dopaminergic neurons and conclude that an ETH-JH-dopamine signaling cascade is required during a critical period for promotion of social-context-dependent memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Aurora kinase A as a possible marker for endocrine resistance in early estrogen receptor positive breast cancer

    DEFF Research Database (Denmark)

    Lykkesfeldt, Anne E; Iversen, Benedikte R; Jensen, Maj-Britt

    2018-01-01

    in 980 tumors and semi quantitively scored into three groups; negative/weak, moderate and high. The Aurora A expression levels were compared to other clinico-pathological parameters and outcome, defined as disease-free survival (DFS) and overall survival (OS). RESULTS: High expression of Aurora......BACKGROUND: Cell culture studies have disclosed that the mitotic Aurora kinase A is causally involved in both tamoxifen and aromatase inhibitor resistant cell growth and thus may be a potential new marker for endocrine resistance in the clinical setting. MATERIAL AND METHODS: Archival tumor tissue...... A was found in 26.9% of patients and moderate in 57.0%. High expression was significantly associated with high malignancy grade and HER2 amplification. High Aurora A expression was significantly more frequent in ductal compared to lobular carcinomas. We found no significant association between Aurora...

  7. Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

    Science.gov (United States)

    Winsauer, Peter J; Sutton, Jessie L

    2014-02-01

    This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

  8. Hormone assay

    International Nuclear Information System (INIS)

    Eisentraut, A.M.

    1977-01-01

    An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

  9. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors

    Directory of Open Access Journals (Sweden)

    Maarten Brom

    2011-03-01

    Full Text Available In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0 showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET, which could improve image quality. Targeting of cholecystokinin-2 (CCK2/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g, indicating CCK2/gastrin receptor-mediated uptake (p = .0005. The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

  10. Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A-like inhibitor of differentiation 1 (EID1

    Directory of Open Access Journals (Sweden)

    Diana Vargas

    2008-01-01

    Full Text Available Transcriptional activation (TA mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A associated 300 kDa binding protein (p300 and the cAMP response element binding protein (CREB binding protein (CBP, known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR mediated TA but the E1A-like inhibitor of differentiation 1 (EID1, an inhibitor of p300 histone acetyltransferase (HAT, is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.

  11. Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

    DEFF Research Database (Denmark)

    Anderson, Richard A; Rosendahl, Mikkel; Kelsey, Thomas W

    2013-01-01

    Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.......Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea....

  12. Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography

    NARCIS (Netherlands)

    Verhagen, Aalt; Luurtsema, Gert; PESSER, JW; DEGROOT, TJ; OOSTERHUIS, JW; Vaalburg, Willem; Wouda, S.

    Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone

  13. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  14. Development and preclinical evaluation of new 124I-folate conjugates for PET imaging of folate receptor-positive tumors

    International Nuclear Information System (INIS)

    AlJammaz, I.; Al-Otaibi, B.; Al-Rumayan, F.; Al-Yanbawi, S.; Amer, S.; Okarvi, S.M.

    2014-01-01

    In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers, we have synthesized [ 124 I]-SIB- and [ 124 I]-SIP-folate conjugates using a straightforward and two-step simple reactions. Radiochemical yields for [ 124 I]-SIB- and [ 124 I]-SIP-folate conjugates were greater than 90 and 60% respectively, with total synthesis time of 30–40 min. Radiochemical purities were always greater than 98% without HPLC purification. These synthetic approaches hold considerable promise as rapid and simple method for 124 I-folate conjugate preparation with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that the significant amounts of the radioconjugates were associated with cell fractions. In vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates and favorable biodistribution profile for [ 124 I]-SIP-folate conjugate over [ 124 I]-SIB-folate conjugate. Biodistribution studies of [ 124 I]-SIP-folate conjugate in nude mice bearing human KB cell line xenografts, demonstrated significant tumor uptake. The uptake in the tumors was blocked by excess injection of folic acid, suggesting a receptor-mediated process. These results demonstrate that [ 124 I]-SIP-folate conjugate may be useful as a molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment

  15. Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer

    Science.gov (United States)

    Fernand ez-Martinez, Aranzazu; Pascual, Tomás; Perrone, Giuseppe; Morales, Serafin; de la Haba, Juan; González-Rivera, Milagros; Galván, Patricia; Zalfa, Francesca; Amato, Michela; Gonzalez, Lucia; Prats, Miquel; Rojo, Federico; Manso, Luis; Paré, Laia; Alonso, Immaculada; Albanell, Joan; Vivancos, Ana; González, Antonio; Matito, Judit; González, Sonia; Fernandez, Pedro; Adamo, Barbara; Muñoz, Montserrat; Viladot, Margarita; Font, Carme; Aya, Francisco; Vidal, Maria; Caballero, Rosalía; Carrasco, Eva; Altomare, Vittorio; Tonini, Giuseppe; Prat, Aleix; Martin, Miguel

    2017-01-01

    PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however, the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0-10% group was 42.7% (with tumor sizes ≤2 cm) and 33.9% (with tumor sizes > 2 cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low-risk outcome patients or Luminal A disease in the clinical setting is unreliable. In the absence of a well-validated prognostic gene expression-based assay, the optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A disease remains at 14%. PMID:28423537

  16. Growth hormone deficiency in a Nigerian child with Turner's syndrome

    African Journals Online (AJOL)

    IRORO YARHERE

    Growth hormone treatment early in the course of management of a child with Turner syndrome may help achieve normal final height. Keywords: Turner's syndrome, short stature, growth hormone deficiency, growth hormone ..... cognitive deficit.

  17. Is the efficacy of hormonal therapy affected by lymph node status? data from the bicalutamide (Casodex) Early Prostate Cancer program

    DEFF Research Database (Denmark)

    Iversen, Peter; Wirth, Manfred P; See, William A

    2004-01-01

    To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalu...

  18. Role of stress-related hormones in plant defence during early infection of the cyst nematode Heterodera schachtii in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Kammerhofer, N.; Radakovic, Z.; Regis, J.M.A.; Dobrev, Petre; Vaňková, Radomíra; Grundler, F.M.W.; Siddique, S.; Hofmann, J.; Wieczorek, K.

    2015-01-01

    Roč. 207, č. 3 (2015), s. 778-789 ISSN 0028-646X R&D Projects: GA MŠk LD14120 Institutional support: RVO:61389030 Keywords : defence responses * early infection * ethylene Subject RIV: ED - Physiology Impact factor: 7.210, year: 2015

  19. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

    Directory of Open Access Journals (Sweden)

    Ji Woo Lee

    2014-09-01

    Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

  20. Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway.

    Science.gov (United States)

    Singh, A S; Shah, A; Brockmann, A

    2018-02-01

    In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr-1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses. © 2017 The Royal Entomological Society.

  1. Prophylactic oral calcium supplementation therapy to prevent early post thyroidectomy hypocalcemia and evaluation of postoperative parathyroid hormone levels to detect hypocalcemia: A prospective randomized study.

    Science.gov (United States)

    Arer, Ilker Murat; Kus, Murat; Akkapulu, Nezih; Aytac, Huseyin Ozgur; Yabanoglu, Hakan; Caliskan, Kenan; Tarim, Mehmet Akin

    2017-02-01

    Postoperative hypocalcemia is the most common complication after total thyroidectomy. Postoperative parathyroid hormone (PTH) measurement is one of the methods to detect or prevent postoperative hypocalcemia. Prophylactic oral calcium supplementation is another method to prevent early postoperative hypocalcemia. The aim of this study is to detect the accurate timing of PTH and evaluate efficacy of routine oral calcium supplementation for postoperative hypocalcemia. A total of 106 patients were performed total thyroidectomy. Rotuine oral calcium supplementation was given to group 1 and no treatment to group 2 according to randomization. Serum calcium and PTH level of patients in group 2 at postoperative 6, 12 and 24 h and patients in both groups at postoperative day 7 were evaluated. Patients were compared according to age, sex, operation findings, serum calcium and PTH levels and symptomatic hypocalcemia. Half of the patients (50%) were in group 1. Most of the patients were female (83%). The most common etiology of thyroid disease was multinodular goiter (64.1%). Oral calcium supplementation was given to 18 (33.9%) patients in group 2. Symptomatic hypocalcemia for group 1 and 2 was found to be 1.9 and 33.9% respectively (p hypocalcemia. Prophylactic oral calcium supplementation therapy can prevent early post-thyroidectomy hypocalcemia with advantages of being cost effective and safe. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  2. The Diagnostic Value of Anti-Müllerian Hormone in Early Post Menarche Adolescent Girls with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Kocaay, Pınar; Siklar, Zeynep; Buyukfirat, Sema; Berberoglu, Merih

    2018-02-17

    Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and chronic anovulation, which affects 5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made easily with clinical and laboratory methods and the anti-Müllerian hormone (AMH) level are accepted as a good indicator. However, there is still no complete consensus on the diagnosis of PCOS in adolescents. Prospective cohort study, December 2013 to November 2014. The study was conducted on adolescent girls with oligomenorrhea, with at least 2 years since menarche. The study group consisted of adolescent girls with complete PCOS and incomplete PCOS. A control group was formed of healthy adolescent girls. Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence of all the following characteristics: oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted as "oligomenorrhea and polycystic ovarian morphology," or "oligomenorrhea and hyperandrogenism." All patients underwent a physical examination and the anthropometric assessments, insulin resistance, and acanthosis nigricans were recorded. It was also noted whether or not the patient had an acne score. The Ferriman-Gallwey score was applied to evaluate hirsutism. The results of this study showed that no statistically significant difference was found between the PCOS and incomplete PCOS groups and the control group with respect to AMH levels. The use of adult-specific diagnostic methods in adolescence might result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  3. Receptor-mediated targeting of 67Ga-Deferoxamine-Folate to folate-receptor-positive human kb tumor xenografts

    International Nuclear Information System (INIS)

    Mathias, Carla J.; Wang, Susan; Low, Philip S.; Waters, David J.; Green, Mark A.

    1999-01-01

    The radiochemical synthesis and stability of 67 Ga-deferoxamine-folate ([ 67 Ga]Ga-DF-Folate) were examined as a function of DF-Folate concentration. Optimal labeling occurred at DF-Folate concentrations ≥2.5 μg/mL. To define the possible biological significance of variations in product formulation, the biodistribution of [ 67 Ga]Ga-DF-Folate was examined as a function of administered deferoxamine-folate dose in an athymic mouse KB tumor model. The folate-receptor-positive KB tumors were found to concentrate the 67 Ga radiolabel in a dose-dependent fashion, consistent with saturable involvement of the folate receptor in mediating tumor accumulation of the radiopharmaceutical

  4. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

    2006-08-10

    The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

  5. A Prospective Comparison of Younger and Older Patients' Preferences for Adjuvant Chemotherapy and Hormonal Therapy in Early Breast Cancer.

    Science.gov (United States)

    Hamelinck, Victoria C; Bastiaannet, Esther; Pieterse, Arwen H; de Glas, Nienke A; Portielje, Johanneke E A; Merkus, Jos W S; den Hoed, Irma D M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan; Stiggelbout, Anne M

    2016-10-01

    It is unknown what minimal benefit in disease-free survival older patients with breast cancer require from adjuvant systemic therapy, and if this differs from that required by younger patients. We prospectively examined patients' preferences for adjuvant chemotherapy (aCT) and adjuvant hormonal therapy (aHT), factors related to minimally-required benefit, and patients' self-reported motivations. Fifty-two younger (40-64 years) and 29 older (≥ 65 years) women with a first primary, invasive tumor were interviewed post-surgery, prior to receiving aCT/aHT recommendation. The proportions of younger versus older participants who would accept, refuse, or were undecided about therapy were 92% versus 62%, 4% versus 24%, and 4% versus 14% for aCT, and 92% versus 59%, 8% versus 17%, and 0% versus 24% for aHT. The proportion of older participants who would refuse rather than accept aCT was larger than that of younger participants (P = .005). No significant difference was found for aHT (P = .12). Younger and older participants' minimally-required benefit, in terms of additional 10-year disease-free survival, to accept aCT (median, 5% vs. 4%; P = .13) or aHT (median, 10% vs. 8%; P = .15) did not differ. Being single/divorced/widowed (odds ratio [OR], 0.16; P = .005), presence of geriatric condition (inability to perform daily activities, incontinence, severe sensory impairment, depression, polypharmacy, difficulties with walking; OR, 0.27; P = .047), and having a preference to make the treatment decision either alone or after considering the clinician's opinion (active role; OR, 0.15; P = .012) were independently related to requiring larger benefits from aCT. The most frequent motivations for/against therapy included the wish to survive/avoid recurrence, clinician's recommendation, side effects, and treatment duration (only aHT). Whereas older participants were less willing to accept aCT than younger participants, no significant difference was found for aHT. However, a

  6. Hormone action. Part I. Peptide hormones

    International Nuclear Information System (INIS)

    Birnbaumer, L.; O'Malley, B.W.

    1985-01-01

    The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

  7. A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    Gu, Ran; Long, Meijun; Chen, Kai; Chen, Lili; Xiao, Qiaozhen; Wu, Mei; Song, Erwei; Su, Fengxi; Jia, Weijuan; Zeng, Yunjie; Rao, Nanyan; Hu, Yue; Li, Shunrong; Wu, Jiannan; Jin, Liang; Chen, Lijuan

    2012-01-01

    In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. Toremifene may be a valid and

  8. NeoPalAna: Neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor positive breast cancer

    Science.gov (United States)

    Ma, Cynthia X.; Gao, Feng; Luo, Jingqin; Northfelt, Donald W.; Goetz, Matthew; Forero, Andres; Hoog, Jeremy; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Anderson, Karen S.; Margenthaler, Julie; Aft, Rebecca; Hobday, Timothy; Moynihan, Timothy; Gillanders, William; Cyr, Amy; Eberlein, Timothy J.; Hieken, Tina; Krontiras, Helen; Guo, Zhanfang; Lee, Michelle V.; Spies, Nicholas C.; Skidmore, Zachary L.; Griffith, Obi L.; Griffith, Malachi; Thomas, Shana; Bumb, Caroline; Vij, Kiran; Bartlett, Cynthia Huang; Koehler, Maria; Al-Kateb, Hussam; Sanati, Souzan; Ellis, Matthew J.

    2017-01-01

    Purpose Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response. Anastrozole was continued until surgery, which occurred 3-5 weeks post palbociclib exposure. Later patients received additional 10-12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression and mutation profiles. The primary endpoint was Complete Cell Cycle Arrest (CCCA: central Ki67<2.7%). Results Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs C1D1 26%, p<0.001). Palbociclib enhanced cell cycle control over anastrozole monotherapy regardless of luminal subtype (A vs B) and PIK3CA status with activity observed across a broad range of clinicopathological and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with non-luminal subtypes and persistent E2F-target gene expression. Conclusions Palbociclib is an active anti-proliferative agent for early-stage breast cancer resistant to anastrozole, however, prolonged administration may be necessary to maintain its effect. PMID:28270497

  9. The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang Jian

    2013-01-01

    Full Text Available Abstract Background Whether PET scan maximum standard uptake value (SUVmax could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC patients with luminal subtype is still unknown and need to be investigated. Methods 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. Results In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS or overall survival (OS after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. Conclusions SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.

  10. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

    Science.gov (United States)

    Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

    2013-12-01

    We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer.

    Science.gov (United States)

    Yamashita, Yuji; Nishiumi, Shin; Kono, Seishi; Takao, Shintaro; Azuma, Takeshi; Yoshida, Masaru

    2017-08-29

    Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. Marked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN.

  12. The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

    International Nuclear Information System (INIS)

    Zhang, Jian; Hu, Xi-Chun; Jia, Zhen; Ragaz, Joseph; Zhang, Ying-Jian; Zhou, Min; Zhang, Yong-Ping; Li, Gang; Wang, Bi-Yun; Wang, Zhong-Hua

    2013-01-01

    Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype

  13. Everolimus plus exemestane versus bevacizumab-based chemotherapy for second-line treatment of hormone receptor-positive metastatic breast cancer in Greece: An economic evaluation study.

    Science.gov (United States)

    Kourlaba, Georgia; Rapti, Vasiliki; Alexopoulos, Athanasios; Relakis, John; Koumakis, Georgios; Chatzikou, Magdalini; Maniadakis, Nikos; Georgoulias, Vassilis

    2015-08-05

    The objective of our study was to conduct a cost-effectiveness (CE) study of combined everolimus (EVE) and exemestane (EXE) versus the common clinical practice in Greece for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer (BC) progressing on nonsteroidal aromatase inhibitors (NSAI). The combinations of bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) were selected as comparators. A Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of the comparators from a third-party payer perspective over a lifetime horizon. Efficacy and safety data as well as utility values considered in the model were extracted from the relevant randomized Phase III clinical trials and other published studies. Direct medical costs referring to the year 2014 were incorporated in the model. A probabilistic sensitivity analysis was conducted to account for uncertainty and variation in the parameters of the model. Primary outcomes were patient survival (life-years), quality-adjusted life years (QALYs), total direct costs and incremental cost-effectiveness ratios (ICER). The discounted quality-adjusted survival of patients treated with EVE plus EXE was greater by 0.035 and 0.004 QALYs, compared to BEV plus PACL and BEV plus CAPE, respectively. EVE plus EXE was the least costly treatment in terms of drug acquisition, administration, and concomitant medications. The total lifetime cost per patient was estimated at €55,022, €67,980, and €62,822 for EVE plus EXE, BEV plus PACL, and BEV plus CAPE, respectively. The probabilistic analysis confirmed the deterministic results. Our results suggest that EVE plus EXE may be a dominant alternative relative to BEV plus PACL and BEV plus CAPE for the treatment of HR+/HER2- advanced BC patients failing initial therapy with NSAIs.

  14. Everolimus use and associated factors among post-menopausal women with hormonal receptor positive/human epidermal growth factor receptor 2 negative metastatic breast cancer.

    Science.gov (United States)

    Li, Nanxin; Hao, Yanni; Xie, Jipan; Lin, Peggy L; Zhou, Zhou; Zhong, Yichen; Signorovitch, James E; Wu, Eric Q

    2015-08-01

    Everolimus has been shown to be an effective HR+/HER2- mBC treatment in both clinical trials and real-world practice. The current study aims at understanding factors associated with everolimus use and how it is used in the real world. A retrospective chart review was conducted among postmenopausal HR+/HER2- mBC women who received everolimus, endocrine therapy (ET), or chemotherapy (CT) for mBC between 1 July 2012 and 15 April 2013 after an NSAI failure. Factors associated with everolimus use versus ET or CT were identified using multivariable logistic regressions. Reasons for prescribing everolimus and everolimus treatment patterns were described. Liver metastasis and high tumor volume were associated with a higher likelihood of everolimus use versus ET (OR = 1.67, OR = 1.62) but a lower likelihood of everolimus use versus CT (OR = 0.43, OR = 0.30). Medicare-only insurance (OR = 0.30) as well as ECOG ≥2 (OR = 3.72) and prior CT in mBC (OR = 2.76) were associated with a lower and higher likelihood of everolimus use versus CT, respectively. The top reason for prescribing everolimus was efficacy (69-85%). About 15% and 29% of everolimus users in second line and third line or above received prior CT for mBC. Exemestane was the most common concomitant therapy with everolimus (56-87%). The majority of patients initiated everolimus at the labeled dose of 10 mg daily (>80%) and maintained this dose (>80%). In the real world, everolimus was used in more severe patients than ET but less severe patients than CT based on visceral metastasis, tumor volume, and performance status. The top reason for prescribing everolimus was efficacy. A large proportion of patients received first or second line CT before everolimus initiation. The majority of patients used everolimus according to the labeled combination and dose. Future studies are needed to determine optimal sequencing of everolimus, ET, and CT for HR+/HER2- mBC.

  15. Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming.

    Science.gov (United States)

    Reynolds, Clare M; Perry, Jo K; Vickers, Mark H

    2017-08-08

    Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as

  16. Basal levels and diurnal variations of some hormones and metabolites in blood of dairy cows treated daily with rbSTin early and late lactation

    Directory of Open Access Journals (Sweden)

    Jurgen Blum

    2010-01-01

    Full Text Available The variations of basal value (before morning feeding at 3-4 days interval and daily pattern (on 4and 18day of treat-  ment with 8 blood collections within 24h of hormones and metabolites were studied in four dairy cows; 2 in early and  2 in late lactation, which were alternatively injected daily for a period of 21 days with 26.3 mg rbST or saline.  The rbST  injection significantly increased the basal and daily levels of GH, IGF-I in both stages of lactation. Daily levels of NEFA  were significantly increased by rbST in both stages of lactation and their variations, due to the effect of meals, were coun-  teracted by the rbST; the higher level of NEFA allowed a greater sparing of glucose, the blood level of which resulted  higher (P  blood urea level (P  ticular the high availability of glucose, determined a significantly higher blood level of insulin and T3, and lower level of  glucagon. Despite the similar GH, IGF-I and NEFA increases observed in the cows treated in early and late lactation, other  metabolic and endocrine consequences resulted more evident in late lactation. Furthermore, some of these variations  were affected by the forage meals. It can be concluded, therefore, that the changes occurring in the blood subsequent  to a rbST treatment are not equal to those which occur at the start of lactation; moreover, they are affected by the daily  feeding pattern and perhaps by the stage of  lactation. 

  17. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

    Science.gov (United States)

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E230 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (PMaca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

  18. Effect of peripartum dietary energy supplementation on thyroid hormones, insulin-like growth factor-i and its binding proteins in early lactation dairy cows

    Directory of Open Access Journals (Sweden)

    Kirovski Danijela

    2012-01-01

    Full Text Available The objective of this study was to examine the effect of dietary energy supplementation on hormones that are considered to be the main signals of a shift in energy balance around parturition. Sixty dry cows, 15 days before calving, were chosen and divided into two eaqual groups: control and experimental (GLY. Both groups were fed a standard ration balanced in accordance to the stage of the productivereproductive cycle. Additionally, each cow in the GLY group was given glycerol based dietary energy supplementation (250 mL daily during the dry and 300 mL daily during the lactation period, which provided additional 9.30 MJ NEL during the dry and 13.95 MJ NEL during the early lactation period. Milk production was measured on days 30 and 60 of lactation and milk production was significantly higher in GLY compared to control group at day 60 of lactation (p<0.05. Service period and insemination index were used as reproductive outcome parameters. Average service period in the control group was significantly longer than in the GLY group (p<0.05. Average insemination index in the control group was not significantly different than the index obtained for the GLY group. Blood samples were taken before the begining of the experiment (15 days before parturition, and at days 7, 30 and 60 of lactation. Concentrations of thyroid hormones, IGF-I, relative abundance of IGFBP-2, IGFBP-3 and IGFBP-4, concentrations of total protein and albumin in the blood were measured. Results showed that at days 7 and 30 after parturition, T4 concentrations were significantly higher (p<0.001, respectively in GLY than in the control group, while T3 concentrations were significantly higher in GLY group only at day 7 after parturition (p<0.001. IGF-I concentrations and IGFBP-3 abundance were significantly higher in the GLY compared to the control group in all three examined postpartum periods. IGFBP-2 and IGFBP-4 concentrations were higher in GLY compared to the control group in all

  19. Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

    Science.gov (United States)

    Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R; Galli, M

    1976-04-20

    Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

  20. Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

    Science.gov (United States)

    Kim, Won Hwa; Cho, Nariya; Kim, Young-Seon; Yi, Ann

    2018-04-06

    To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

  1. Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Francescopaolo Di Cello

    Full Text Available Downregulation of the tight junction protein claudin 1 is a frequent event in breast cancer and is associated with recurrence, metastasis, and reduced survival, suggesting a tumor suppressor role for this protein. Tumor suppressor genes are often epigenetically silenced in cancer. Downregulation of claudin 1 via DNA promoter methylation may thus be an important determinant in breast cancer development and progression. To investigate if silencing of claudin 1 has an epigenetic etiology in breast cancer we compared gene expression and methylation data from 217 breast cancer samples and 40 matched normal samples available through the Cancer Genome Atlas (TCGA. Moreover, we analyzed claudin 1 expression and methylation in 26 breast cancer cell lines. We found that methylation of the claudin 1 promoter CpG island is relatively frequent in estrogen receptor positive (ER+ breast cancer and is associated with low claudin 1 expression. In contrast, the claudin 1 promoter was not methylated in most of the ER-breast cancers samples and some of these tumors overexpress claudin 1. In addition, we observed that the demethylating agents, azacitidine and decitabine can upregulate claudin 1 expression in breast cancer cell lines that have a methylated claudin 1 promoter. Taken together, our results indicate that DNA promoter methylation is causally associated with downregulation of claudin 1 in a subgroup of breast cancer that includes mostly ER+ tumors, and suggest that epigenetic therapy to restore claudin 1 expression might represent a viable therapeutic strategy in this subtype of breast cancer.

  2. [Everolimus plus exemestane in postmenopausal patients with estrogen-receptor-positive advanced breast cancer - Japanese subgroup analysis of BOLERO -2].

    Science.gov (United States)

    Ito, Yoshinori; Masuda, Norikazu; Iwata, Hiroji; Mukai, Hirofumi; Horiguchi, Jun; Tokuda, Yutaka; Kuroi, Katsumasa; Mori, Asuka; Ohno, Nobutsugu; Noguchi, Shinzaburo

    2015-01-01

    In a phase 3, double-blind, randomized, international study (the BOLERO-2), the addition of mTOR inhibitor everolimus to exemestane was evaluated in postmenopausal women with estrogen-receptor-positive (ER⁺) advanced/recurrent breast cancer that was refractory to any nonsteroidal aromatase inhibitor (NSAI). This report presents the safety and updated (18- month) efficacy results from the Japanese subset (n=106) of BOLERO-2. After a median follow-up of 18 months, the median progression-free survival time was 8.5 months with everolimus plus exemestane compared to 4.2 months with placebo plus exemestane. The most common adverse events (AEs) with everolimus plus exemestane were stomatitis, rash, dysgeusia, and non-infectious lung disease. The AEs reported with the combination therapy were mostly of grade 1 or 2 and manageable with appropriate intervention. In conclusion, this combination could be a useful addition to the armamentarium of treatments for Japanese postmenopausal women with ER⁺ advanced/recurrent breast cancer progressing on NSAIs.

  3. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

    DEFF Research Database (Denmark)

    Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

    2016-01-01

    . However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

  4. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  5. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  6. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study.

    Science.gov (United States)

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Kapczynski, W; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This was a double-blind, randomized, placebo-corrected, outpatient, multi-centre (five sites) clinical study, in which a total of 168 Caucasian early-postmenopausal women volunteers (age>49 years) participated after fulfilling the criteria: follicle stimulating hormone (FSH) >30 IU/ml and estrogen (E2) Maca (Maca-GO) treatment, according to different monthly treatment sequences scheduled for each site. Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day) during three (Trial I; n=102) or four (Trial II; n=66) months study periods. At the baseline and follow- up monthly intervals, blood levels of FSH, E2, progesterone (PRG) and lutinizing hormone (LH), as well as serum cholesterol (CHOL), triglycerides (TRG), high- and low density lipoproteins (HDL and LDL) were measured. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly results in one model and Maca versus Placebo contrast in another model. A total of 124 women concluded the study. Maca-GO significantly stimulated production of E2 (PMaca-GO significantly reduced both frequency and severity of individual menopausal symptoms (hot flushes and night sweating in particular) resulting in significant (P<0.001) alleviation of KMI (from 22 to 10), thus, offering an attractive non-hormonal addition to the choices available to early-postmenopausal women in the form of a natural plant alternative to Hormone Replacement Therapy (HRT) - hence, reducing dependence on hormone therapy programs.

  7. GABAA receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine in rhesus monkeys.

    Science.gov (United States)

    Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

    2017-09-01

    GABA A receptor positive allosteric modulators (GABA A receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABA A receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABA A receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self-administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABA A receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABA A receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABA A receptor modulator temazepam decreasing the behavioral and neurochemical effects

  8. Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

    Science.gov (United States)

    Cai, Siwei; Yang, Qianhui; Hou, Mengzhu; Han, Qian; Zhang, Hanyu; Wang, Jiantao; Qi, Chen; Bo, Qiyu; Ru, Yusha; Yang, Wei; Gu, Zhongxiu; Wei, Ruihua; Cao, Yunshan; Li, Xiaorong; Zhang, Yan

    2018-01-01

    Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested

  9. Relation of estrogen receptor-alpha gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women.

    Science.gov (United States)

    Salmén, Timo; Heikkinen, Anna-Mari; Mahonen, Anitta; Kröger, Heikki; Komulainen, Marja; Saarikoski, Seppo; Honkanen, Risto; Partanen, Juhani; Mäenpää, Pekka H

    2002-01-01

    Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-alpha (ER alpha) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women. We studied the influence of the ER alpha genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ER alpha gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ER alpha genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ER alpha genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ER alpha genotype. In conclusion, ER alpha polymorphism is associated with fall risk

  10. The role of releasing hormones in the diagnosis of hypopituitarism ...

    African Journals Online (AJOL)

    Luteinising hormone-releasing factor and thyrotrophinreleasing factor were used in conjunction with the insulin tolerance test in 9 patients with known or suspected panhypopituitarism. It appears that growth hormone and luteinising hormone fail early in panhypopituitarism. Cortisol and thyroid-stimulating hormone ...

  11. Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature

    International Nuclear Information System (INIS)

    Tutt, Andrew; Shu, Henry; Springall, Robert; Cane, Paul; McCallie, Blair; Kam-Morgan, Lauren; Anderson, Steve; Buerger, Horst; Gray, Joe; Bennington, James; Esserman, Laura; Wang, Alice; Hastie, Trevor; Broder, Samuel; Sninsky, John; Brandt, Burkhard; Waldman, Fred; Rowland, Charles; Gillett, Cheryl; Lau, Kit; Chew, Karen; Dai, Hongyue; Kwok, Shirley; Ryder, Kenneth

    2008-01-01

    Given the large number of genes purported to be prognostic for breast cancer, it would be optimal if the genes identified are not confounded by the continuously changing systemic therapies. The aim of this study was to discover and validate a breast cancer prognostic expression signature for distant metastasis in untreated, early stage, lymph node-negative (N-) estrogen receptor-positive (ER+) patients with extensive follow-up times. 197 genes previously associated with metastasis and ER status were profiled from 142 untreated breast cancer subjects. A 'metastasis score' (MS) representing fourteen differentially expressed genes was developed and evaluated for its association with distant-metastasis-free survival (DMFS). Categorical risk classification was established from the continuous MS and further evaluated on an independent set of 279 untreated subjects. A third set of 45 subjects was tested to determine the prognostic performance of the MS in tamoxifen-treated women. A 14-gene signature was found to be significantly associated (p < 0.05) with distant metastasis in a training set and subsequently in an independent validation set. In the validation set, the hazard ratios (HR) of the high risk compared to low risk groups were 4.02 (95% CI 1.91–8.44) for the endpoint of DMFS and 1.97 (95% CI 1.28 to 3.04) for overall survival after adjustment for age, tumor size and grade. The low and high MS risk groups had 10-year estimates (95% CI) of 96% (90–99%) and 72% (64–78%) respectively, for DMFS and 91% (84–95%) and 68% (61–75%), respectively for overall survival. Performance characteristics of the signature in the two sets were similar. Ki-67 labeling index (LI) was predictive for recurrent disease in the training set, but lost significance after adjustment for the expression signature. In a study of tamoxifen-treated patients, the HR for DMFS in high compared to low risk groups was 3.61 (95% CI 0.86–15.14). The 14-gene signature is significantly

  12. Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer.

    Science.gov (United States)

    O'Shaughnessy, J; Campone, M; Brain, E; Neven, P; Hayes, D; Bondarenko, I; Griffin, T W; Martin, J; De Porre, P; Kheoh, T; Yu, M K; Peng, W; Johnston, S

    2016-01-01

    Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. NCT01381874. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

  13. Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer†

    Science.gov (United States)

    O'Shaughnessy, J.; Campone, M.; Brain, E.; Neven, P.; Hayes, D.; Bondarenko, I.; Griffin, T. W.; Martin, J.; De Porre, P.; Kheoh, T.; Yu, M. K.; Peng, W.; Johnston, S.

    2016-01-01

    Background Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients and methods Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0–1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. Results There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82–1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70–1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). Conclusions Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. ClinicalTrials.gov NCT01381874. PMID:26504153

  14. Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

    International Nuclear Information System (INIS)

    Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L.

    2006-01-01

    In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis

  15. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  16. Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sri Lakshmi Hyndavi Yeruva

    2015-01-01

    Full Text Available Aromatase inhibitors (AIs are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.

  17. A portion of heifers attaining “early puberty” do not display estrus, are anovulatory and have altered sex hormone binding globulin concentrations

    Science.gov (United States)

    Cows with excess androstenedione (High A4) in the follicular fluid of dominant follicles attain puberty earlier than their low androstenedione counterparts. Furthermore, High A4 cows are anovulatory (chronic or sporadic) and have lower Sex Hormone Binding Globulin (SHBG) compared to Low A4 ovulator...

  18. Initial water deficit effects on Lupinus albus photosynthetic performance, carbon metabolism, and hormonal balance: metabolic reorganization prior to early stress responses

    Czech Academy of Sciences Publication Activity Database

    Pinheiro, C.; António, C.; Dobrev, Petre; Vaňková, Radomíra; Wilson, J. C.

    2011-01-01

    Roč. 62, č. 14 (2011), s. 4965-4974 ISSN 0022-0957 Institutional research plan: CEZ:AV0Z50380511 Keywords : Carbon metabolism * hormone balance * LC-MS Subject RIV: EF - Botanics Impact factor: 5.364, year: 2011

  19. Early changes of thyroid hormone concentrations after {sup 131}I therapy in Graves' patient pretreated or not with methimazole

    Energy Technology Data Exchange (ETDEWEB)

    Pirnat, E.; Zaletel, K.; Gabercsek, S.; Fidler, V.; Hojker, S. [University Medical Centre, Ljubljana (Slovenia). Dept. of Nuclear Medicine

    2004-08-01

    Aim: Despite extensive use of {sup 131}I therapy for Graves' hyperthyroidism the treatment regimen with {sup 131}I and antithyroid drugs remain under discussion. In our prospective clinical study we followed acute thyroid hormone changes after {sup 131}I in patients not pretreated with methimazole (MMI) and in patients with different MMI pretreatment regimes. Patients, methods: 187 patients were treated with fixed activity of 550 or 740 MBq of {sup 131}I. First group (71 patients) received {sup 131}I alone. In the second group (57 patients) MMI was stopped seven days before {sup 131}I. The third group (59 patients) received MMI until {sup 131}I application. Initial free triodothyronin and free thyroxin were measured in the second group 7 and 2 days before {sup 131}I therapy and in all three groups on the day of {sup 131}I application as well as 2, 5, 12, and 30 days afterwards. Absorbed dose was measured in each patient. Results: In the non-pretreated group {sup 131}I application was followed by a significant decrease of fT{sub 4} in 5 days and of fT{sub 3} in 2 days, higher reduction was detected in patients with higher baseline values. In MMI pretreated patients significant but clinically irrelevant increase of both thyroid hormones was detected with maximum value 7 days after discontinuation in the second group and 5 days after discontinuation in the third group. Additionally, in patients of the third group absorbed dose of {sup 131}I was significantly lower relative to other two groups. We found no correlation between absorbed dose of {sup 131}I and thyroid hormone changes. Conclusion: Our study demonstrates that {sup 131}I application alone does not result in exacerbation of hyperthyroidism and therefore it may be considered as safe. Additionally, MMI withdrawal causes significant but clinically irrelevant elevation of thyroid hormones. (orig.)

  20. Thyroid stimulating hormone and subclinical thyroid dysfunction

    International Nuclear Information System (INIS)

    Guo Yongtie

    2008-01-01

    Subclinical thyroid dysfunction has mild clinical symptoms. It is nonspecific and not so noticeable. It performs only for thyroid stimulating hormone rise and decline. The value of early diagnosis and treatment of thyroid stimulating hormone in subclinical thyroid dysfunction were reviewed. (authors)

  1. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  2. Factors influencing the uptake of {sup 18}F-fluoroestradiol in patients with estrogen receptor positive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Lanell M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Kurland, Brenda F. [Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Link, Jeanne M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Schubert, Erin K. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Stekhova, Svetlana [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, WA (United States); Mankoff, David A., E-mail: dam@u.washington.edu [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States)

    2011-10-15

    Introduction: {sup 18}F-Fluoroestradiol (FES) PET imaging provides a non-invasive method to measure estrogen receptor (ER) expression in tumors. Assessment of factors that could affect the quantitative level of FES uptake is important as part of the validation of FES PET for evaluating regional ER expression in breast cancer. Methods: This study examines FES uptake in tumors from 312 FES PET scans (239 patients) with documented ER+ primary breast cancer. FES uptake was compared to clinical and laboratory data, treatment prior to or at time of scan, and properties of FES and its metabolism and transport. Linear mixed models were used to explore univariate, threshold-based and multivariate associations. Results: Sex hormone-binding globulin (SHBG) was inversely associated with FES SUV. Average FES uptake did not differ by levels of plasma estradiol, age or rate of FES metabolism. FES tumor uptake was greater for patients with a higher body mass index (BMI), but this effect did not persist when SUV was corrected for lean body mass (LBM). In multivariate analysis, only plasma SHBG binding was an independent predictor of LBM-adjusted FES SUV. Conclusions: Calculation of FES SUV, possibly adjusted for LBM, should be sufficient to assess FES uptake for the purpose of inferring ER expression. Pre-menopausal estradiol levels do not appear to interfere with FES uptake. The availability and binding properties of SHBG influence FES uptake and should be measured. Specific activity did not have a clear influence on FES uptake, except perhaps at higher injected mass per kilogram. These results suggest that FES imaging protocols may be simplified without sacrificing the validity of the results.

  3. An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells

    International Nuclear Information System (INIS)

    Mandal, Soma; Davie, James R

    2007-01-01

    The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation. Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+)ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO), enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. In all GO terms, biological process (BP), molecular function (MF), and cellular component (CC), MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1) and glucose metabolism (MCF-7). A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, glycolysis/gluconeogenesis) and expression (ribosome) in both cells, there was an overall similarity of ZR75-1 with ER(-)ve cell lines and ER(+)ve/ER(-)ve breast tumors. This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A) in representative ER(+)ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+)ve breast tumors

  4. 17β-estradiol induces stearoyl-CoA desaturase-1 expression in estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Belkaid, Anissa; Duguay, Sabrina R.; Ouellette, Rodney J.; Surette, Marc E.

    2015-01-01

    To sustain cell growth, cancer cells exhibit an altered metabolism characterized by increased lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the production of monounsaturated fatty acids that are essential for membrane biogenesis, and is required for cell proliferation in many cancer cell types. Although estrogen is required for the proliferation of many estrogen-sensitive breast carcinoma cells, it is also a repressor of SCD-1 expression in liver and adipose. The current study addresses this apparent paradox by investigating the impact of estrogen on SCD-1 expression in estrogen receptor-α-positive breast carcinoma cell lines. MCF-7 and T47D mammary carcinomas cells and immortalized MCF-10A mammary epithelial cells were hormone-starved then treated or not with 17β-estradiol. SCD-1 activity was assessed by measuring cellular monounsaturated/saturated fatty acid (MUFA/SFA) ratios, and SCD-1 expression was measured by qPCR, immunoblot, and immunofluorescence analyses. The role of SCD-1 in cell proliferation was measured following treatment with the SCD-1 inhibitor A959372 and following SCD-1 silencing using siRNA. The involvement of IGF-1R on SCD-1 expression was measured using the IGF-1R antagonist AG1024. The expression of SREBP-1c, a transcription factor that regulates SCD-1, was measured by qPCR, and by immunoblot analyses. 17β-estradiol significantly induced cell proliferation and SCD-1 activity in MCF-7 and T47D cells but not MCF-10A cells. Accordingly, 17β-estradiol significantly increased SCD-1 mRNA and protein expression in MCF-7 and T47D cells compared to untreated cells. Treatment of MCF-7 cells with 4-OH tamoxifen or siRNA silencing of estrogen receptor-α largely prevented 17β-estradiol-induced SCD-1 expression. 17β-estradiol increased SREBP-1c expression and induced the mature active 60 kDa form of SREBP-1. The selective SCD-1 inhibitor or siRNA silencing of SCD-1 blocked the 17β-estradiol-induced cell proliferation and increase in

  5. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

    Science.gov (United States)

    O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

    2018-03-01

    CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

  6. OctreoScan 111 for imaging of a somatostatin receptor-positive islet cell tumor in rat

    International Nuclear Information System (INIS)

    Bruns, C.; Stolz, B.; Albert, R.; Marbach, P.; Pless, J.

    1993-01-01

    We report here the in vitro characterization of SDZ 215-811 and the in vivo imaging of a islet cell tumor gown in rats using [ 111 In]SDZ 215-811. In vitro autoradiographies revelaed a high density of SRIF receptors on the pancreatic tumor tissue. As early as 5 min after intravenous injection of [ 111 In]SDZ 215-811 into tumour-bearing rats, the tumors were clearly localized by gamma-camera scintigraphy. Even 24 h post injection, the islet cell tumor was still detectable. The radioligand was mainly cleared from the circulation via the Kidneys, with a rapid α-phase (t 1/2 =5.6 min) and a slow elimination phase (t 1/2 =7.3 h). Biodistribution studies revealed a relatively high accumulation of radioactivity in the kidneys, but low uptake into the liver and the intestine. High uptake of [ 111 In]SDZ 215-811 was observed for the tumor tissue (0.92±0.07% ID/g; 1 h post injection). Interestingly, a tumor load of 0.14±0.01% ID/g was still measured after 24 h. The tumor/blood ratio was 4.93 after 24 h, indicating specific accumulation of radioactivity in the islet cell tumour. [ 111 In]SDZ 215-811 appears to be sensitive and specific ligand for SRIF receptorpositive tumors and offers an easy procedure for scintigraphic imaging of such tumors in man. (orig.)

  7. Efficacy of dendritic cells matured early with OK-432 (Picibanil), prostaglandin E2, and interferon-alpha as a vaccine for a hormone refractory prostate cancer cell line.

    Science.gov (United States)

    Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong; Kim, Choung-Soo

    2010-09-01

    Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

  8. Electrochemical biosensors for hormone analyses.

    Science.gov (United States)

    Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

    2015-06-15

    Electrochemical biosensors have a unique place in determination of hormones due to simplicity, sensitivity, portability and ease of operation. Unlike chromatographic techniques, electrochemical techniques used do not require pre-treatment. Electrochemical biosensors are based on amperometric, potentiometric, impedimetric, and conductometric principle. Amperometric technique is a commonly used one. Although electrochemical biosensors offer a great selectivity and sensitivity for early clinical analysis, the poor reproducible results, difficult regeneration steps remain primary challenges to the commercialization of these biosensors. This review summarizes electrochemical (amperometric, potentiometric, impedimetric and conductometric) biosensors for hormone detection for the first time in the literature. After a brief description of the hormones, the immobilization steps and analytical performance of these biosensors are summarized. Linear ranges, LODs, reproducibilities, regenerations of developed biosensors are compared. Future outlooks in this area are also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.; Stein, J.

    2017-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

  10. Fundamental considerations in the design of fluorine-18 labeled progestins and androgens as imaging agents for receptor-positive tumors of the breast and prostate

    International Nuclear Information System (INIS)

    Brandes, S.J.; Katzenellenbogen, J.A.

    1988-01-01

    A review is given of the structural and functional features which are important in the design and development of imaging agents for the progesterone receptor (PR) and the androgen receptor (AR) directed towards imaging receptor-positive tumors in the breast and prostate respectively. In particular the effects of various substituents on the biological activities and homologous receptor binding of progesterone, testosterone, nortestosterone and dihydrotestosterone are discussed. The effect of fluorine substitution on the affinities of progestins and androgens for their respective receptors is described. Other ligand systems that have high affinity for AR and PR and which may provide good bases for the design of fluorine-substituted imaging agents are also discussed. Finally, previous studies with radiolabelled progestins and androgens are described. (U.K.)

  11. Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

    Science.gov (United States)

    Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Rodriguez-Cortés, Jeanette; Pedraza-López, Martha; Ramírez-Iglesias, María Teresa

    2006-04-01

    Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours. To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours. HYNIC was conjugated to the epsilon-amino group of Lys 3 residue at the N-terminal region of bombesin via succinimidyl-N-Boc-HYNIC at pH 9.0. 99mTc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer pH 7.0 to a lyophilized formulation. Stability studies were carried out by reversed phase HPLC and ITLC-SG analyses in serum and cysteine solutions. In-vitro internalization was tested using human prostate cancer PC-3 cells with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in PC-3 tumour-bearing nude mice. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin was obtained with radiochemical purities >93% and high specific activity ( approximately 0.1 GBq.nmol). Results of in-vitro studies demonstrated a high stability in serum and cysteine solutions, specific cell receptor binding and rapid internalization. Biodistribution data showed a rapid blood clearance, with predominantly renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas and PC-3 tumours. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin obtained from lyophilized kit formulations has promising characteristics for the diagnosis of malignant tumours that over-express the GRP receptor.

  12. Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

    Science.gov (United States)

    Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

    2013-04-01

    Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

  13. Maternal Early Life Factors Associated with Hormone Levels and the Risk of Having a Child with an Autism Spectrum Disorder in the Nurses Health Study II

    Science.gov (United States)

    Lyall, Kristen; Pauls, David L.; Santangelo, Susan; Spiegelman, Donna; Ascherio, Alberto

    2011-01-01

    It is not known whether reproductive factors early in the mother's life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in…

  14. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms

    NARCIS (Netherlands)

    Yam, K.Y.; Naninck, E.F.G.; Schmidt, M.V.; Lucassen, P.J.; Korosi, A.

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the

  15. Early Stress Causes Sex-Specific, Life-Long Changes in Behaviour, Levels of Gonadal Hormones, and Gene Expression in Chickens

    NARCIS (Netherlands)

    Elfwing, Magnus; Natt, Daniel; Goerlich - Jansson, Vivian; Persson, Mia; Hjelm, Jonas; Jensen, Per

    2015-01-01

    Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of

  16. Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens.

    Directory of Open Access Journals (Sweden)

    Magnus Elfwing

    Full Text Available Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of stress experienced during the first weeks of life. Chicks from a commercial egg-laying hybrid were exposed to stress by inducing periods of social isolation during their first three weeks of life, followed by a broad behavioural, physiological and genomic characterization throughout life. Early stressed males, but not females, where more anxious in an open field-test, stayed shorter in tonic immobility and tended to have delayed sexual maturity, as shown by a tendency for lower levels of testosterone compared to controls. While early stressed females did not differ from non-stressed in fear and sexual maturation, they were more socially dominant than controls. The differential gene expression profile in hypothalamus was significantly correlated from 28 to 213 days of age in males, but not in females. In conclusion, early stress had a more pronounced long-term effect on male than on female chickens, as evidenced by behavioral, endocrine and genomic responses. This may either be attributed to inherent sex differences due to evolutionary causes, or possibly to different stress related selection pressures on the two sexes during commercial chicken breeding.

  17. A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study

    DEFF Research Database (Denmark)

    Viljakainen, H.T.; Palssa, A.; Karkkainen, M.

    2006-01-01

    -six girls, mean age 11 center dot 4 (sd 0 center dot 4) years, in Tanner stage 2 (early puberty) and 3 (mid-puberty) were studied during September to March. The BMD was measured from the lumbar vertebrae and the left femur by dual-energy X-ray absoptiometry. Their serum 25-hydroxyvitamin D (S-25-OHD), serum...

  18. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Nations, Kari R; Dogterom, Peter; Bursi, Roberta; Schipper, Jacques; Greenwald, Scott; Zraket, David; Gertsik, Lev; Johnstone, Jack; Lee, Allen; Pande, Yogesh; Ruigt, Ge; Ereshefsky, Larry

    2012-12-01

    Org 26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to explore safety, tolerability, pharmacokinetics, and pharmacodynamics of Org 26576 in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD) and optimal titration schedule in a multiple rising dose paradigm (range 100 mg BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID, 400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based on the number of moderate intensity adverse events reported at the 600 mg BID dose level, the MTD established in Part I was 450 mg BID. Symptomatic improvement as measured by the Montgomery-Asberg Depression Rating Scale was numerically greater in the Org 26576 groups than in the placebo group in both study parts. In Part II, the 400 mg BID dose was associated with improvements in executive functioning and speed of processing cognitive tests. Org 26576 was also associated with growth hormone increases and cortisol decreases at the end of treatment but did not influence prolactin or brain-derived neurotrophic factor. The quantitative electroencephalogram index Antidepressant Treatment Response at Week 1 was able to significantly predict symptomatic response at endpoint in the active treatment group, as was early improvement in social acuity. Overall, Org 26576 demonstrated good tolerability and pharmacokinetic properties in depressed patients, and pharmacodynamic endpoints suggested that it may show promise in future well-controlled, adequately powered proof of concept trials.

  19. [Sexual hormone and traditional Chinese patent medicine for early postmenopausal women: effect on quality of life and cost-utility analysis].

    Science.gov (United States)

    Zhou, Ling-Ling; Xu, Liang-Zhi; Liu, Hong-Wei; Zhang, Jing; Liu, Ying; Liu, Xiao-Fang; Tang, Liu-Lin; Zhuang, Jing; Liu, Xiao-Xian; Qiao, Lin

    2009-11-01

    To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women. Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA). At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis. At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.

  20. Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

    Science.gov (United States)

    Generali, Daniele; Corona, Silvia Paola; Pusztai, Lajos; Rouzier, Roman; Allevi, Giovanni; Aguggini, Sergio; Milani, Manuela; Strina, Carla; Frati, Albane

    2018-03-01

    Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

  1. A Study on BRCA1/2 Mutations, Hormone Status and HER-2 Status in Korean Women with Early-onset Breast Cancer

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Jin, So Young; Lee, Dong Wha; Kim, Eun Seog; Kim, Yong Ho

    2008-01-01

    Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history (4/14) and bilateral breast cancers (3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2- associated cancers demonstrated more expression of ER-negative (19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors (negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was

  2. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer

    Science.gov (United States)

    Felder, Tisha M.; Do, D. Phuong; Lu, Z. Kevin; Lal, Lincy S.; Heiney, Sue P.; Bennett, Charles L.

    2016-01-01

    Purpose Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone-receptor positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. Methods We evaluated 494 study-eligible, Black (n=255) and White women (n=269) who were under 65 years old and diagnosed with stages I–III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥ 1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Results Seventy-two percent of the participants were ever-users (70% Black, 74% White) and 68% were early-users (65% Black, 71% White) of AHT. Neither ever-use (adjusted OR (AOR)=0.75, 95% CI: 0.48–1.17) nor early-use (AOR=0.70, 95% CI: 0.46–1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR= 2.15, 95% CI: 1.35–3.44); chemotherapy (AOR=1.97, 95% CI: 1.22–3.20); radiation (AOR=2.33, 95% CI: 1.50–3.63); early-use: receipt of surgery (AOR=2.03, 95% CI: 1.30–3.17); chemotherapy (AOR=1.90, 95% CI: 1.20–3.03); radiation (AOR=1.73, 95% CI: 1.14–2.63)]. Conclusions No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation. PMID:27120468

  3. Lower levels of placental growth hormone in early pregnancy in women with type 1 diabetes and large for gestational age infants

    DEFF Research Database (Denmark)

    Ringholm, Lene; Juul, Anders; Pedersen-Bjergaard, Ulrik

    2015-01-01

    and median HbA1c 6.6% (range 4.9-10.5) (49 mmol/mol (30-91)) in early pregnancy. At 8, 14, 21, 27 and 33 weeks weight was recorded and blood was sampled for measurements of placental GH, IGF-I and HbA1c. LGA was defined as birth weight >90th percentile after adjustment for gender and gestational age. RESULTS......,multivariate logistic regression analysis identified placental GH levels at 8 weeks (OR 0.4 (95% CI: 0.2-0.9), p = 0.02), HbA1c at 33 weeks (3.6 (1.3-9.9), p = 0.01) and parity ≥1 (3.1 (1.3-7.5), p = 0.01) after adjustment for pre-pregnancy BMI. CONCLUSIONS: Women delivering LGA infants had lower placental GH levels...

  4. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

    International Nuclear Information System (INIS)

    Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

    2016-01-01

    Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

  5. Menopause and Hormones

    Science.gov (United States)

    ... Consumer Information by Audience For Women Menopause and Hormones: Common Questions Share Tweet Linkedin Pin it More ... reproduction and distribution. Learn More about Menopause and Hormones Menopause--Medicines to Help You Links to other ...

  6. Thyroid Hormone Treatment

    Science.gov (United States)

    ... THYROID HORMONES? Desiccated ( dried and powdered ) animal thyroid ( Armour ®), now mainly obtained from pigs, was the most ... hormone can increase the risk or heart rhythm problems and bone loss making the use of thyroxine ...

  7. Antidiuretic hormone blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003702.htm Antidiuretic hormone blood test To use the sharing features on this page, please enable JavaScript. Antidiuretic blood test measures the level of antidiuretic hormone (ADH) in ...

  8. Hormonal effects in newborns

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb, babies ...

  9. Growth hormone stimulation test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

  10. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Thangavelu, Pulari U; Lin, Cheng-Yu; Vaidyanathan, Srividya; Nguyen, Thu H M; Dray, Eloise; Duijf, Pascal H G

    2017-09-22

    During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas. CENPI mRNA and protein levels are significantly elevated in estrogen receptor-positive (ER+) but not in estrogen receptor-negative (ER-) breast carcinoma. Well-established prognostic tests indicate that CENPI overexpression constitutes a powerful independent marker for poor patient prognosis and survival in ER+ breast cancer. We further demonstrate that CENPI is an E2F target gene. Consistently, it is overexpressed in RB1 -deficient breast cancers. However, CENP-I overexpression is not purely due to cell cycle-associated expression. In ER+ breast cancer cells, CENP-I overexpression promotes CIN, especially chromosome gains. In addition, in ER+ breast carcinomas the degree of CENPI overexpression is proportional to the level of aneuploidy and CENPI overexpression is one of the strongest markers for CIN identified to date. Our results indicate that overexpression of the inner kinetochore protein CENP-I promotes CIN and forecasts poor prognosis for ER+ breast cancer patients. These observations provide novel mechanistic insights and have important implications for breast cancer diagnostics and potentially therapeutic targeting.

  11. Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Petruolo, Oriana A; Pilewskie, Melissa; Patil, Sujata; Barrio, Andrea V; Stempel, Michelle; Wen, Hannah Y; Morrow, Monica

    2017-09-01

    The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR). The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC. Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP). From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.

  12. Preparation and evaluation of a new neurotensin analog labeled with 99mTc for targeted imaging of neurotensin receptor positive tumors

    International Nuclear Information System (INIS)

    Nakisa Zarrabi Ahrabi; Kazem Parivar; Davood Beiki

    2014-01-01

    Neurotensin receptors are overexpressed in several human tumors and can be targets for tumors diagnosis and therapy. In this study, a new neurotensin analogue was labeled with 99m Tc via HYNIC and tricine/EDDA as coligands and investigated further. [HYNIC 0 , Gly 7 , Lys 9 , d-Tyr 11 ]-Neurotensin (7-13) was synthesized using a standard Fmoc strategy. Labeling with 99m Tc was performed at 100 deg C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of humane serum at 37 deg C up to 24 h. The receptor bound internalization and externalization rates were studied in neurotensin receptor expressing HT-29 cells. Biodistribution of radiopeptide was studied in nude mice bearing HT-29 tumor. Labeling yield of 98.6 ± 0.54 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed specific internalization into HT-29 cells (12.43 ± 0.52 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in neurotensin receptor positive organs so that after 1 h the uptakes in mouse intestine and tumor were 0.87 ± 0.16 and 0.63 ± 0.12 % ID/g respectively. (author)

  13. 99mTc-HYNIC-somatostatin analogues for imaging SST receptor positive tumours, preclinical evaluation and comparison with 111In-Octreotide

    International Nuclear Information System (INIS)

    Decristoforo, C.; Melendez-Alafort, L.; Sosabowski, J.K.; Mather, S.J.

    2001-01-01

    HYNIC-TOC and HYNIC-RC-160 were prepared and radiolabelled at high specific activities using tricine, EDDA and tricine/nicotinic acid as co-ligand systems. Radioligand binding assays were performed on membranes prepared from receptor-positive cell lines. Biodistribution and tumour uptake were determined in AR42J tumour bearing nude mice and compared to 99m Tc-MAG-3-RC-160 and 111 In-DTPA-Octreotide. Specific tumour uptake between 2.4 and 9.6%ID/g was found for the 99m Tc labelled HYNIC-conjugates compared to 0.2% for the 99m Tc-MAG-3-RC-160 and 4.3% ID/g for 111 In-DTPA-Octreotide. RC-160 conjugates showed lower tumour uptake and greater hepatobiliary excretion than TOC. Tricine as co-ligand showed higher levels of radioactivity in muscle, blood and liver, while tricine/NA produced significant levels of activity in the GI-tract. EDDA showed the most promising overall biodistribution profile with similar tumour: liver and GI-tract ratios to those obtained with 111 In-DTPA-Octreotide, lower ratios in blood and muscle but considerably higher tumour/kidney ratios. (author)

  14. Thyroid hormone-dependent development of early cortical networks: Temporal specificity and the contribution of trkB and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Sören eWesterholz

    2013-08-01

    Full Text Available Early in neocortical network development, triiodothyronine (T3 promotes GABAergic neurons’ population increase, their somatic growth and the formation of GABAergic synapses. In the presence of T3, GABAergic interneurons form longer axons and conspicuous axonal arborizations, with an increased number of putative synaptic boutons. Here we show that the increased GABAergic axonal growth is positively correlated with the proximity to non-GABAergic neurons. A differential innervation emerges from a T3-dependent decrease of axonal length in fields with low density of neuronal cell bodies, combined with an increased bouton formation in fields with high density of neuronal somata. T3 addition to deprived networks after the first two weeks of development did not rescue deficits in the GABAergic synaptic bouton distribution, or in the frequency and duration of spontaneous bursts. During the critical two-week-period, GABAergic signaling is depolarizing as revealed by calcium imaging experiments. Interestingly, T3 enhanced the expression of the potassium-chloride cotransporter 2 (KCC2, and accelerated the developmental shift from depolarizing to hyperpolarizing GABAergic signaling in non-GABAergic neurons.The T3-related increase of spontaneous network activity was remarkably reduced after blockade of either tropomyosin-receptor kinase B (trkB or mammalian target of rapamycin (mTOR pathways. T3-dependent increase in GABAergic neurons’ soma size was mediated mainly by mTOR signaling. Conversely, the T3-dependent selective increase of GABAergic boutons near non-GABAergic cell bodies is mediated by trkB signaling only. Both trkB and mTOR signaling mediate T3-dependent reduction of the GABAergic axon extension. The circuitry context is relevant for the interaction between T3 and trkB signaling, but not for the interactions between T3 and mTOR signaling.

  15. Indução hormonal da ovulação e desmame precoce na fertilidade pós-parto de vacas de corte homozigotas e heterozigotas para o microssatélite BMS3004 Hormonal induction of ovulation and early weaning in postpartum fertility of homozigous and heterozigous beef cows for the microsatellite BMS3004

    Directory of Open Access Journals (Sweden)

    Guilherme de Medeiros Bastos

    2003-10-01

    , associated to the temporary weaning for 96 hours, with the definitive weaning at 60 days in beef cows, for the induction of estrus and ovulation. One hundred and eighty-three suckled beef cows were used. The breeds of the cows were Charolais (C and Nellore (N and their crosses. The animals were genotyped as homozygous (HOM and heterozigous (HET for the microsatellite BMS3004, that is localized in the same chromossome of the LH beta chain gene. The cows were distributed in two groups between 60 and 80 days postpartum (day 0. In the hormonal induction group (HI, the cows (n=87 received (day 0 250 mg of medroxiprogesteron acetate for 8 days, 2.5 mg of estradiol benzoate (day 1 and 500 UI of eCG (day 7. On day 8, the calves were weaned for 96 hours. In the same day (day 8, the cows (n=96 of the other group were just submitted to early weaning (group EW. Twelve hours after weaning, artificial insemination (AI was done during four days. After this period, they were mated. The first diagnosis of pregnancy (DP was performed 60 days after the AI period and, the second, 60 days after the end of mating. The estrus rates were higher in cows from HI group than in those of EW group. In the HI group, the cows with body condition 2.5 and 3.0 presented lower pregnancy rates at the 1st DP (29.6 and 46.4% than in the EW group (56.0 and 72.2%. The rates of pregnancy in cows with body index 65-73 did not differ between the HI and EW groups. The N cows of HI group presented lower pregnancy rate at 1st DP than the F1 (27.7 vs. 64.2%, but was not different than the C cows (40.0%. In the HI group, the pregnancy rate at the 2nd DP was lower in HOM cows than in the HET ones. The cows in the early definitive weaning group showed to be more efficient than in the hormonal induction group to improve the pregnancy rate.

  16. Analysis of PI3K/mTOR Pathway Biomarkers and Their Prognostic Value in Women with Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hamdy A. Azim

    2016-04-01

    Full Text Available BACKGROUND: The PI3K/AKT/mTOR pathway alterations have been shown to play significant roles in the development, progression, and metastatic spread of breast cancer. Furthermore, they have been implicated in the process of drug resistance, especially endocrinal therapies. In this study, we aimed to define the correlation between the PI3K mutations and the expression of the phosphorylated forms of different downstream molecules in women with estrogen receptor (ER–positive, human epidermal growth factor receptor 2–negative (luminal early breast cancer treated at Cairo university hospitals. METHODS: Next-generation sequencing was used to detect mutations in the PIK3CA hotspots (in exons 9 and 20. Immunohistochemistry was performed on tissue microarray blocks prepared from samples of 35 Egyptian luminal breast cancer patients in the pathology department of Centre Léon Bérard (CLB. The intensity and the percentage of stained tumor cells were integrated to define high versus low biomarker expression. The cytoplasmic and nuclear stainings were graded separately. Patients were followed for a median of 4.7 years (2.1 to 6.9 years. Correlation was done between PI3K mutations and the immunohistochemistry expression of pAKT, LKB1, p4EBP1, and pS6 ribosomal protein (pS6RP with the clinicopathologic features and disease free survival (DFS of the patients. RESULTS: Median age at diagnosis was 51.3 years (range, 25 to 82 years. Tumors were larger than 20 mm in 79.2% of the cases, whereas 57.9% had axillary lymph node deposits. Only 12.3% of the patients had SBR grade I tumors, 50.8% had grade II, and 36.8% had grade III. ERs were negative in 6 patients (17% after pathology review. Thirty-two cases were assessable for LKB1 and pAKT, 33 for p4EBP1 and pS6RP, and 24 for PI3K mutations. Nuclear LKB1, cytoplasmic LKB1, nuclear pAKT, cytoplasmic pAKT, nuclear p4EBP1, and cytoplasmic pS6RP expression was high in 65.6%, 62.5%, 62.5%, 68.8%, 42.4%, and 57

  17. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial.

    Science.gov (United States)

    Royce, Melanie; Bachelot, Thomas; Villanueva, Cristian; Özgüroglu, Mustafa; Azevedo, Sergio J; Cruz, Felipe Melo; Debled, Marc; Hegg, Roberto; Toyama, Tatsuya; Falkson, Carla; Jeong, Joon; Srimuninnimit, Vichien; Gradishar, William J; Arce, Christina; Ridolfi, Antonia; Lin, Chinjune; Cardoso, Fatima

    2018-03-22

    Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). Patients received first-line treatment with everolimus, 10 mg/d, plus letrozole, 2.5 mg/d. Second-line treatment with everolimus, 10 mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. The primary end point was investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95% CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7% (95% CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95% CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4

  18. Effects of GABA-B receptor positive modulator on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in freely moving rats.

    Science.gov (United States)

    Ma, Jingyi; Stan Leung, L

    2017-10-01

    Decreased GABA B receptor function is proposed to mediate some symptoms of schizophrenia. In this study, we tested the effect of CGP7930, a GABA B receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats. Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats. CGP7930 or vehicle was injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.), alone or 15 min prior to ketamine (3 mg/kg, subcutaneous) injection. Paired click auditory evoked potentials in the hippocampus (AEP), prepulse inhibition (PPI), and locomotor activity were recorded before and after drug injection. CGP7930 at doses of 1 mg/kg (i.p.) prevented ketamine-induced deficit of PPI. CGP7930 (1 mg/kg i.p.) also prevented the decrease in gating of hippocampal AEP and the increase in hippocampal gamma (65-100 Hz) waves induced by ketamine. Unilateral i.c.v. infusion of CGP7930 (0.3 mM/1 μL) also prevented the decrease in gating of hippocampal AEP induced by ketamine. Ketamine-induced behavioral hyperlocomotion was suppressed by 5 mg/kg i.p. CGP7930. CGP7930 alone, without ketamine, did not significantly affect integrated PPI, locomotion, gating of hippocampal AEP, or gamma waves. CGP7930 (1 mg/kg i.p.) increased heterosynaptically mediated paired pulse depression in the hippocampus, a measure of GABA B receptor function in vivo. CGP7930 reduces the behavioral and electrophysiological disruptions induced by ketamine in animals, and the hippocampus may be one of the neural targets where CGP7930 exerts its actions.

  19. Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

    Science.gov (United States)

    Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

    2008-07-15

    Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

  20. 99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours

    International Nuclear Information System (INIS)

    Guggenberg, E. von; Gabriel, M.; Virgolini, I.J.; Decristoforo, C.; Dietrich, H.; Skvortsova, I.

    2007-01-01

    Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA 0 ,DGlu 1 ]minigastrin (DTPA-MG0) radiolabelled with 111 In and 90 Y, our group developed a 99m Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC 0 ,DGlu 1 ,desGlu 2-6 ]minigastrin (HYNIC-MG11). 99m Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. 99m Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of 99m Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. 99m Tc-EDDA-HYNIC-MG11 shows advantages over 99m Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement. (orig.)

  1. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Adler, Lenard A; Kroon, René A; Stein, Mark; Shahid, Mohammed; Tarazi, Frank I; Szegedi, Armin; Schipper, Jacques; Cazorla, Pilar

    2012-12-01

    It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org 26576 was investigated with a translational approach including preclinical and clinical testing. Neonatal rat 6-hydroxydopamine lesion-induced hyperactivity was used as preclinical model. Seventy-eight ADHD adults entered a multicenter, double-blind, placebo-controlled, two-period crossover trial. After 1 week placebo lead-in, 67 subjects were randomized into one of four treatment sequences: sequence A (n = 15) Org 26576 (100 mg b.i.d.) for 3 weeks, followed by a 2-week placebo crossover and 3 weeks placebo; sequence B (n = 16) 5 weeks placebo followed by 3 weeks Org 26576 (100 mg b.i.d.); sequence C (n = 18) Org 26576 flexible dose (100-300 mg b.i.d.) for 3 weeks, then 5 weeks placebo; sequence D (n = 18) 5 weeks placebo followed by 3 weeks Org 26576 (100-300 mg b.i.d.). The Adult ADHD Investigator Symptom Rating Scale was used to assess changes in ADHD symptomatology. Org 26576 (1, 3, 10 mg/kg intraperitoneal) produced dose-dependent inhibition of locomotor hyperactivity in 6-hydroxydopamine-lesioned rats. Org 26576 (100 mg b.i.d.) was superior to placebo in treating symptoms of adult ADHD subjects. The primary Adult ADHD Investigator Symptom Rating Scale results were supported by some secondary analyses. However, Org 26576 (100-300 mg b.i.d.) did not confirm these results. Most frequently reported adverse events were nausea, dizziness, and headache. These preclinical and clinical findings suggest that Org 25676 may have utility in the treatment of ADHD. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jammaz, I. Al, E-mail: jammaz@kfshrc.edu.sa; Al-Otaibi, B.; Amer, S.; Okarvi, S.M.

    2011-10-15

    In an attempt to visualize folate receptors that overexpress on many cancers, [{sup 18}F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([{sup 18}F]-1, [{sup 18}F]-2-folates and [{sup 18}F]-8, [{sup 18}F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [{sup 18}F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [{sup 18}F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [{sup 18}F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [{sup 18}F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response

  3. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

    International Nuclear Information System (INIS)

    Jammaz, I. Al; Al-Otaibi, B.; Amer, S.; Okarvi, S.M.

    2011-01-01

    In an attempt to visualize folate receptors that overexpress on many cancers, [ 18 F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([ 18 F]-1, [ 18 F]-2-folates and [ 18 F]-8, [ 18 F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [ 18 F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [ 18 F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [ 18 F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [ 18 F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.

  4. Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Anna Miquel-Cases

    Full Text Available Guiding response to neoadjuvant chemotherapy (guided-NACT allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial.As effectiveness was shown in hormone-receptor positive (HR+ early breast cancers (EBC, our decision model compared the health-economic outcomes of treating a cohort of such women with guided-NACT to conventional-NACT using clinical input data from the GeparTrio trial. The expected cost-effectiveness and the uncertainty around this estimate were estimated via probabilistic cost-effectiveness analysis (CEA, from a Dutch societal perspective over a 5-year time-horizon.Our exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY cost-effectiveness was expected with 78% certainty.This exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.

  5. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

    Science.gov (United States)

    Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

    2012-03-01

    Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

  6. Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression.

    Science.gov (United States)

    Kent, Justine M; Daly, Ella; Kezic, Iva; Lane, Rosanne; Lim, Pilar; De Smedt, Heidi; De Boer, Peter; Van Nueten, Luc; Drevets, Wayne C; Ceusters, Marc

    2016-06-03

    This phase 2a, randomized, multicenter, double-blind, proof-of-concept study was designed to evaluate, efficacy, safety and tolerability of JNJ-40411813/ADX71149, a novel metabotropic glutamate 2 receptor positive allosteric modulator as an adjunctive treatment for major depressive disorder (MDD) with significant anxiety symptoms. Eligible patients (18-64 years) had a DSM-IV diagnosis of MDD, Hamilton Depression Rating Scale-17 (HDRS17) score of ≥ 18, HDRS17 anxiety/somatization factor score of ≥ 7, and an insufficient response to current treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. The doubly-randomized, 8-week double-blind treatment phase was comprised of two 4-week periods, from which a combined test statistic was generated, with pre-determined weights assigned to each of the 2 treatment periods. Period 1: patients (n=121) were randomly assigned (1:1) to JNJ-40411813 (n=62; 50mg to 150 mg b.i.d, flexibly dosed) or placebo (n=59); Period 2: placebo-treated patients (n=22) who continued to meet entry severity criteria were re-randomized (1:1) to JNJ-40411813 or placebo, while other patients underwent sham re-randomization and continued on their same treatment. Of 121 randomized patients, 100 patients (82.6%) were completers. No efficacy signal was detected on the primary endpoint, the 6-item Hamilton Anxiety Subscale (HAM-A6, p=0.51). Efficacy signals (based on prespecified 1-sided pdepression (HDRS17 total score, 6-item subscale of HDRS17 assessing core depressive symptoms [HAM-D6], and Inventory of Depressive Symptomatology [IDS-C30]) and anxiety (HDRS17 anxiety/somatization factor, IDS-C30 anxiety subscale). Although well-tolerated, the results do not suggest efficacy for JNJ-40411813 as an adjunctive treatment for patients with MDD with significant anxious symptoms in the dose range studied. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

    Directory of Open Access Journals (Sweden)

    Chen Jing

    2010-04-01

    Full Text Available Abstract Background The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs. Methods The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip, provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. Results We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+ and MDA-MB-231 (estrogen receptor negative, ER- breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. Conclusion This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular

  8. Evaluation of the ability of adjuvant tamoxifen-benefit gene signatures to predict outcome of hormone-naive estrogen receptor-positive breast cancer patients treated with tamoxifen in the advanced setting

    DEFF Research Database (Denmark)

    Sieuwerts, Anieta M; Lyng, Maria Bibi; Meijer-van Gelder, Marion E

    2014-01-01

    and NAT1 were significantly associated with a favorable PFS in multivariate analysis that included the traditional predictive factors: age, dominant relapse site, disease-free interval, ER and progesterone receptor (PGR), and adjuvant chemotherapy. This study shows that BCAR3, BCL2 and NAT1 in particular...

  9. Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer.

    Science.gov (United States)

    Yamamoto, Yutaka; Ishikawa, Takashi; Hozumi, Yasuo; Ikeda, Masahiko; Iwata, Hiroji; Yamashita, Hiroko; Toyama, Tatsuya; Chishima, Takashi; Saji, Shigehira; Yamamoto-Ibusuki, Mutsuko; Iwase, Hirotaka

    2013-05-16

    After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating. TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE. UMIN000001841.

  10. Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer

    International Nuclear Information System (INIS)

    Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Iwase, Hirotaka; Ishikawa, Takashi; Hozumi, Yasuo; Ikeda, Masahiko; Iwata, Hiroji; Yamashita, Hiroko; Toyama, Tatsuya; Chishima, Takashi; Saji, Shigehira

    2013-01-01

    After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM. When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating. TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function

  11. Reproductive Hormones and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2010-12-01

    Full Text Available During the menstrual cycle, pregnancy and breast-feeding periods, as well as in menopausal and post-menopausal periods, the physiological and psychological processes that change according to the hormonal fluctuations influence every women similarly and each one differently. These physiological processes are controlled by neuroendocrine sequences, of which the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis are the most important ones. The hypothalamo-pituitary-gonadal axis affects mood, anxiety, cognition and pain. The interaction of these hormones with mood and behavior is bidirectional. The differences in phenomenology and epidemiology of mood disorders with regards to gender can be explained with the effects of hormones. All of the periods mentioned above are related with mood disorders at terms of risk factors, disease symptoms, progress of disease and response to treatment. Epidemiologic data supports the relationship between the mood disorders and reproductive processes. The prevalence of major depression increases in women with the menarche and ceases in post- menopausal period. Similarly, the initial symptoms of bipolar disorder begins around the menarche period in 50% of the cases. Despite proper treatment, some female patients with major depression experience recurrence during the premenstrual period of their menstrual cycles. The conformity and change in a woman’s brain during pregnancy is controlled dominantly by the neuroendocrine systems, while it is controlled by the external stimuli actively related to the baby during nursing period. The changes that occur are closely related to postpartum mood disorders. Again, all the changes and suspension of medication during this procedure are risk factors for early depressive and dysphoric situations. Variables of a wide range, from follicle stimulating hormone, melatonin, and sleep to body mass index interact with mood disorders in menopausal and post

  12. Psychomotor retardation in a girl with complete growth hormone deficiency.

    Science.gov (United States)

    Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

    2013-01-01

    Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

  13. Radioimmunoassay of thyroid hormones

    International Nuclear Information System (INIS)

    Bartalena, L.; Mariotti, S.; Pinchera, A.

    1987-01-01

    For many years, methods based on iodine content determination have represented the only techniques available for the estimation of total thyroid hormone concentrations in serum. Subsequently, simple, sensitive, and specific radioligand assays for thyroid hormones have replaced these chemical methods. For the purpose of this chapter, iodometric techniques are only briefly summarized for their historical importance, whereas attention is focused on radioligand assays

  14. Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

    Science.gov (United States)

    Nuzzo, F; Gallo, C; Lastoria, S; Di Maio, M; Piccirillo, M C; Gravina, A; Landi, G; Rossi, E; Pacilio, C; Labonia, V; Di Rella, F; Bartiromo, A; Buonfanti, G; De Feo, G; Esposito, G; D'Aniello, R; Maiolino, P; Signoriello, S; De Maio, E; Tinessa, V; Colantuoni, G; De Laurentiis, M; D'Aiuto, M; Di Bonito, M; Botti, G; Giordano, P; Daniele, G; Morabito, A; Normanno, N; de Matteis, A; Perrone, F

    2012-08-01

    To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

  15. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  16. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  17. Aging changes in hormone production

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

  18. Hormonal changes in secondary impotence

    International Nuclear Information System (INIS)

    Salama, F.M.; El-Shabrawy, N.O.; Nosseir, S.A.; Abo El-Azayem, Naglaa.

    1985-01-01

    Impotence is one of the problems which is still obscure both in its aetiology and treatment. The present study deals with the possible hormonal changes in cases of secondary infertility. The study involved 25 patients diagnosed as secondary impotence. Hormonal assay was performed for the following hormones: 1. Prolaction hormone. 2. Luteinising hormone (L.H.). 3. Testosterone. 4. Follicle stimulating hormone (F.S.H.). The assay was carried out by radioimmunoassay using double antibody technique. Results are discussed

  19. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic

    2004-01-01

    of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2......The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...

  20. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    Science.gov (United States)

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  1. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  2. Developmental programming: the role of growth hormone.

    Science.gov (United States)

    Oberbauer, Anita M

    2015-01-01

    Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

  3. Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

    Science.gov (United States)

    Glaser, Rebecca L; Dimitrakakis, Constantine

    2014-06-01

    Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

  4. The relationship of luteinizing hormone secretion to sleep in women during the early follicular phase: effects of sleep reversal and a prolonged three-hour sleep-wake schedule.

    Science.gov (United States)

    Kapen, S; Boyar, R; Hellman, L; Weitzman, E D

    1976-06-01

    The relationship of luteinizing hormone (LH) secretion to sleep in adult women was investigated in two ways: an acute 180 degrees sleep-wake cycle reversal in a group of six women and a schedule in which a young woman engaged in a three hour sleep-wake cycle (two hours awake, one hour allowed for sleep continuously for ten days--the study was carried out on the eighth day). Each subject in the reversal study had a baseline period during which plasma samples were collected every twenty minutes for twenty-four hours and nocturnal sleep was monitored electrophysiologically during the early follicular phase of the menstrual cycle. During a succeeding cycle, the study was repeated after sleep-wake reversal. LH secretory patterns were analyzed by comparing the 24-hour mean plasma LH concentration with the hourly averages in percentage terms, using Stage 2 sleep onset as the zero point. LH secretion was depressed to approximately the same degree in both the baseline and reversal studies. The average hourly percentage difference from the 24-hour mean for the four-hour period following sleep onset was -13.4% and -13.1% for the baseline and reversal, respectively. These percentage deviations represented practically the entire negative deviation for the 24-hour period in both studies. The difference between the first four-hour period after sleep onset and the second was significant. The subject on a three-hour cycle had a baseline in which a large decrease in LH secretion occurred after sleep onset (-52.2% during the third hour). Her LH secretory pattern during the three-hour sleep-wake schedule was characterized by a fall during sleep periods, particularly when slow wave sleep (SWS) predominated. However, no correlation was found between specific sleep stages and LH secretion in the six women of the reversal study. These results confirm a relationship of LH secretion to sleep in adult women, one which is different from that described during puberty.

  5. Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)

    Science.gov (United States)

    Cintron, Dahima; Lahr, Brian D.; Bailey, Kent R.; Santoro, Nanette; Lloyd, Robin; Manson, JoAnn E.; Neal-Perry, Genevieve; Pal, Lubna; Taylor, Hugh S.; Wharton, Whitney; Naftolin, Fredrick; Harman, S. Mitchell; Miller, Virginia M.

    2018-01-01

    Abstract Objective: This study determined whether two different formulations of hormone therapy (HT): oral conjugated equine estrogens (o-CEE; 0.45 mg/d, n = 209), transdermal 17β-estradiol (t-E2; 50 μg/d, n = 201) plus cyclic progesterone (Prometrium, 200 mg) or placebo (PBO, n = 243) affected sleep domains in participants of the Kronos Early Estrogen Prevention Study. Methods: Participants completed the Pittsburgh Sleep Quality Index at baseline and during the intervention at 6, 18, 36, and 48 months. Global sleep quality and individual sleep domain scores were compared between treatments using analysis of covariance, and correlated with vasomotor symptom (VMS) scores using Spearman correlation coefficients. Results: Global Pittsburgh Sleep Quality Index scores (mean 6.3; 24% with score >8) were similar across groups at baseline and were reduced (improved sleep quality) by both HT (average change −1.27 [o-CEE] and −1.32 [t-E2]) when compared with PBO (−0.60; P = 0.001 [o-CEE vs PBO] and P = 0.002 [t-E2 vs PBO]). Domain scores for sleep satisfaction and latency improved with both HT. The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO. Global sleep scores significantly correlated with VMS severity (rs = 0.170, P < 0.001 for hot flashes; rs = 0.177, P < 0.001 for night sweats). Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS. Conclusions: Poor sleep quality is common in recently menopausal women. Sleep quality improved with both HT formulations. The relationship of VMS with domains of sleep suggests that assessing severity of symptoms and domains of sleep may help direct therapy to improve sleep for postmenopausal women. PMID:28832429

  6. Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen-receptor positive, but not HER-2 breast cancer

    Science.gov (United States)

    Smolarek, Amanda K.; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S.; Suh, Nanjoo

    2012-01-01

    Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ- or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). While administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (ptocopherol treatment groups by 42% (ptocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of pro-apoptotic markers (BAX, cleaved-caspase 9, cleaved-caspase 3, cleaved-PARP) were increased, while anti-apoptotic markers (Bcl2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKC α), survival (PPARγ, PTEN, phospho-Akt) and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, appear to be promising agents for the prevention of hormone-dependent breast cancer. PMID:22964476

  7. Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer.

    Science.gov (United States)

    Smolarek, Amanda K; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S; Suh, Nanjoo

    2012-11-01

    Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P tocopherol treatment groups by 42% (P tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.

  8. Hormones and Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Resources • Find-an-Endocrinologist: www.hormone.org or ...

  9. Growth hormone test

    Science.gov (United States)

    ... is called acromegaly . In children it is called gigantism . Too little growth hormone can cause a slow ... growth due to excess GH during childhood, called gigantism. (A special test is done to confirm this ...

  10. Longitudinal reproductive hormone profiles in infants

    DEFF Research Database (Denmark)

    Andersson, A M; Toppari, J; Haavisto, A M

    1998-01-01

    The gonads are usually considered quiescent organs in infancy and childhood. However, during the first few postnatal months of life, levels of gonadotropins and sex hormones are elevated in humans. Recent epidemiological evidence suggests that environmental factors operating perinatally may...... influence male reproductive health in adulthood. The early postnatal activity of the Sertoli cell, a testicular cell type that is supposed to play a major role in sperm production in adulthood is largely unknown. Recently, the peptide hormone inhibin B was shown to be a marker of Sertoli cell function......, and testosterone. Thus, although levels of FSH, LH, and testosterone decreased into the range observed later in childhood by the age of 6-9 months, serum inhibin B levels remained elevated up to at least the age of 15 months. In girls, the hormonal pattern was generally more complex, with a high interindividual...

  11. Growth Hormone-Releasing Hormone in Diabetes

    Directory of Open Access Journals (Sweden)

    Leonid Evsey Fridlyand

    2016-10-01

    Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

  12. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  13. Heterogeneity of protein hormones

    Energy Technology Data Exchange (ETDEWEB)

    Rosselin, G; Bataille, D; Laburthe, M; Duran-Garcia, S [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Saint-Antoine, 75 - Paris (France)

    1975-12-01

    Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasmas and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight form is still little known. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, simulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms ofenteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones.

  14. Kinetics of thyroid hormones

    International Nuclear Information System (INIS)

    Inada, Mitsuo; Nishikawa, Mitsushige; Naito, Kimikazu; Ishii, Hitoshi; Tanaka, Kiyoshi

    1980-01-01

    Kinetics of thyroid hormones were outlined, and recent progress in metabolism of these hormones was also described. Recently, not only T 4 and T 3 but also rT 3 , 3,3'-T 2 , 3',5'-T 2 , and 3,5-T 2 can be measured by RIA. To clarify metabolic pathways of these hormones, metabolic clearance rate and production rate of these hormones were calculated. As single-compartment analysis was insufficient to clarify disappearance curves of thyroid hormones in blood such as T 3 and T 2 of which metabolic speed was so fast, multi-compartment analysis or non-compartment analysis were also performed. Thyroid hormones seemed to be measured more precisely by constant infusion method. At the first step of T 4 metabolism, T 3 was formed by 5'-monodeiodination of T 4 , and rT 3 was formed by 5-monodeiodination of T 4 . As metabolic pathways of T 3 and rT 3 , conversion of them to 3,3'-T 2 or to 3',5'-T 2 and 3,5-T 2 was supposed. This subject will be an interesting research theme in future. (Tsunoda, M.)

  15. Bulimia from a gynecological view: hormonal changes.

    Science.gov (United States)

    Resch, M; Szendei, G; Haász, P

    2004-11-01

    Gynecological problems are one of the most frequent somatic complications of eating disorders. The purpose of the present study was to assess the role of improper eating habits in the aetiology of menstrual disturbances, anovulation and hormonal related changes. Bulimia nervosa is the focus of attention since amenorrhea is considered a diagnostic criterium in anorexia nervosa. Subjects of the BITE (Bulimia Investigation Test, Edinburgh) test who were infertile were studied (n = 58) In the studied population there were 6 cases of clinical and 8 cases of subclinical bulimia nervosa. Symptoms and severity subscales of the BITE test significantly correlated with body mass index (p = 0.003). All 14 patients suffering from clinical and subclinical bulimia nervosa had pathologically low FSH and LH hormone levels. In those with clinical bulimia nervosa (n = 6) we diagnosed 4 cases of multicystic ovary (MCO) and in the eating disorder not otherwise specified (EDNOS) group (n = 22) there were 2 cases of MCO and 5 cases of polycystic ovary syndrome (PCOS). The results suggest that unsatisfactory nutrition (binges and "crash diet") in bulimia nervosa results in hormonal dysfunction, menstrual disturbances and infertility. The authors question the necessity for immediately estrogen replacement: they consider the reversibility of the hormonal status by early treatment of eating disorders is more appropriate. Excessive use of hormonal contraceptives in therapy has to be questioned.

  16. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: A randomized, double-blind, placebo controlled study

    NARCIS (Netherlands)

    Brink, E.; Coxam, V.; Robins, S.; Wahala, K.; Cassidy, A.; Branca, F.

    2008-01-01

    Background: Osteoporosis is a major health problem. It was hypothesized that isoflavone-containing products may be a potential alternative to hormone replacement therapy for preventing bone loss during the menopausal transition. Objective: The objective was to investigate whether the consumption of

  17. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

    DEFF Research Database (Denmark)

    Kolsen-Petersen, J A; Bendtzen, K; Tonnesen, E

    2008-01-01

    Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery.......Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery....

  18. Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

    Science.gov (United States)

    Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

    2007-08-01

    Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

  19. Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors

    International Nuclear Information System (INIS)

    Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

    2007-01-01

    Purpose: Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with 99m Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC 0 ), 1-Nal 3 , Thr 8 ]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Methods: Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with 99m Tc was performed at 100 o C for 10 min using SnCl 2 as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr 2 -expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Results: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr 2 . The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13±0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33±0.23%ID/g (percentage of injected dose per gram of tissue). Conclusion: These data show that [ 99m Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies

  20. Transmission of F4+ E. coli in groups of early weaned piglets

    NARCIS (Netherlands)

    Geenen, P.L.; Döpfer, D.; Meulen, van der J.; Jong, de M.C.M.

    2005-01-01

    The aim of this study was to estimate transmission parameters of enterotoxigenic F4+ Escherichia coli F4 (F4+ E. coli) in groups of early weaned piglets with F4-receptor-positive (F4R+) and F4-receptor-negative piglets (F4R[minus sign]). Transmission of F4+ E. coli was quantified in four

  1. Hormonal control of euryhalinity

    Science.gov (United States)

    Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  2. Headache And Hormones

    Directory of Open Access Journals (Sweden)

    Shukla Rakesh

    2002-01-01

    Full Text Available There are many reasons to suggest a link between headache and hormones. Migraine is three times common in women as compared to men after puberty, cyclic as well as non-cyclic fluctuations in sex hormone levels during the entire reproductive life span of a women are associated with changes in frequency or severity of migraine attack, abnormalities in the hypothalamus and pineal gland have been observed in cluster headache, oestrogens are useful in the treatment of menstrual migraine and the use of melatonin has been reported in various types of primary headaches. Headache associated with various endocrinological disorders may help us in a better understanding of the nociceptive mechanisms involved in headache disorders. Prospective studies using headache diaries to record the attacks of headache and menstrual cycle have clarified some of the myths associated with menstrual migraine. Although no change in the absolute levels of sex hormones have been reported, oestrogen withdrawal is the most likely trigger of the attacks. Prostaglandins, melatonin, opioid and serotonergic mechanisms may also have a role in the pathogenesis of menstrual migraine. Guidelines have been published by the IHS recently regarding the use of oral contraceptives by women with migraine and the risk of ischaemic strokes in migraineurs on hormone replacement therapy. The present review includes menstrual migraine, pregnancy and migraine, oral contraceptives and migraine, menopause and migraine as well as the hormonal changes in chronic migraine.

  3. [Hormones and hair growth].

    Science.gov (United States)

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  4. Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

    DEFF Research Database (Denmark)

    Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

    2018-01-01

    response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

  5. Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

    Science.gov (United States)

    Foley, Niamh M; Coll, J M; Lowery, A J; Hynes, S O; Kerin, M J; Sheehan, M; Brodie, C; Sweeney, K J

    2017-09-11

    Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

  6. Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors.

    Science.gov (United States)

    Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman

    2011-11-20

    The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

  7. Hormonal causes of recurrent pregnancy loss (RPL).

    Science.gov (United States)

    Pluchino, Nicola; Drakopoulos, Panagiotis; Wenger, Jean Marie; Petignat, Patrick; Streuli, Isabelle; Genazzani, Andrea Riccardo

    2014-01-01

    Endocrine disorders play a major role in approximately 8% to 12% of recurrent pregnancy loss (RPL). Indeed, the local hormonal milieu is crucial in both embryo attachment and early pregnancy. Endocrine abnormalities, including thyroid disorders, luteal phase defects, polycystic ovary syndrome, hyperprolactinaemia and diabetes have to be evaluated in any case of RPL. Moreover, elevated androgen levels and some endocrinological aspects of endometriosis are also factors contributing to RPL. In the present article, we review the significance of endocrine disease on RPL.

  8. Stress and hormones

    Directory of Open Access Journals (Sweden)

    Salam Ranabir

    2011-01-01

    Full Text Available In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves′ disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.

  9. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  10. Hormonal homeostasis in lung cancer patients under combined and radiation treatment

    International Nuclear Information System (INIS)

    Zotova, I.A.; Firsova, P.P.; Matveenko, E.G.

    1984-01-01

    Radioimmunoassay of hormonal homeostasis was performed in 200 lung cancer patients before and after combined and radiation treatment and in 25 healthy subjects (controls). The study showed an increase in the basal level of hormones of pituitary - adrenal system matched by a decline in thyroid function. Adequate combined and radiation treatment brought hormone levels to normal. Hormonal disorders accompanying recurrence were identical to those registered at disease onset. In some cases, changes in hormonal homeostasis developed as early as 3-6 months prior to clinically manifest recurrences or dissemination

  11. Radioimmunoassay of steroid hormone

    International Nuclear Information System (INIS)

    Murakami, Tadashi

    1975-01-01

    Low acid pepsin treated gamma-globulin was applied to ammonium sulfate salting out method, which was a method to separate bound fraction from free one in radioimmunoassay of steroid hormone, and the effect of the separation and the standard curve were examined. Pepsin treated gamma-globulin was prepared in pH 1.5 to 5.5 and then the pepsin was completely removed. It had an effect to accelerate the precipitation in radioimmunoassay of steroid hormone labelled with 3 H. The effect of pepsin treated gamma-globulin to adhere free steroid hormone and to slat out bound one was compared with that of human gamma-globulin. Pepsin treated gamma-globulin, which was water soluble, could easier reach its optimal concentration, and the separation effect was better than human gamma-globulin. The standard curve of it was steeper, particularly in a small dose, and the reproducibility was also better. It could be applied not only to aldosterone and DOC, but also to the steroid hormones, such as progesterone and DHEA, and it seemed suitable for routine measurement method. (Kanao, N.)

  12. Hormones and social preferences

    NARCIS (Netherlands)

    Buser, T.

    2011-01-01

    We examine whether social preferences are determined by hormones. We do this by investigating whether markers for the strength of prenatal testosterone exposure (finger length ratios) and current exposure to progesterone and oxytocin (the menstrual cycle) are correlated with choices in social

  13. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  14. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  15. Inappropriate Antidiuretic Hormone Secretion

    African Journals Online (AJOL)

    1974-06-08

    Jun 8, 1974 ... with Addison's disease, diarrhoea or salt-losing nephritis. (asymptomatic hyponatraemia).~ Schwartz et al.3 stud;ed two patients with anaplastic bronchus carcinoma and hyponatraemia in 1957, and they suggested that there was an inappropriate secretion of antidiuretic hormone (ADH). It is now well ...

  16. Radioimmunoassay of protein hormones

    International Nuclear Information System (INIS)

    Talas, M.; Fingerova, H.

    1976-01-01

    A survey is presented of the history of RIA methods for FSH, LH, HCG, HPL and prolactin determinations with special regard to the double antibody method in a kinetic system. Problems are shown in 125 I-labelling protein hormones in preparing own antisera. (L.O.)

  17. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  18. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

  19. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  20. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

  1. Radioimmunoassay of polypeptide hormones and enzymes

    International Nuclear Information System (INIS)

    Felber, J.P.

    1974-01-01

    General principles of radioimmunoassay are reviewed. Detailed procedures are reviewed for the following hormones: insulin, pituitary hormones, gonadotropins, parathyroid hormone, ACTH, glucagon, gastrin, and peptide hormones. Radioimmunoassay of enzymes is also discussed. (U.S.)

  2. DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67 status of estrogen receptor-positive breast cancers

    KAUST Repository

    Fan, Ming

    2017-12-08

    Breast tumor heterogeneity is related to risk factors that lead to worse prognosis, yet such heterogeneity has not been well studied.To predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer patients via analysis of tumor heterogeneity with subgroup identification based on patterns of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Retrospective study.Seventy-seven breast cancer patients with ER-positive breast cancer were investigated, of whom 51 had low Ki-67 expression.T1 -weighted 3.0T DCE-MR images.Each tumor was partitioned into multiple subregions using three methods based on patterns of dynamic enhancement: 1) time to peak (TTP), 2) peak enhancement rate (PER), and 3) kinetic pattern clustering (KPC). In each tumor subregion, 18 texture features were computed.Univariate and multivariate logistic regression analyses were performed using a leave-one-out-based cross-validation (LOOCV) method. The partitioning results were compared with the same feature extraction methods across the whole tumor.In the univariate analysis, the best-performing feature was the texture statistic of sum variance in the tumor subregion with early TTP for differentiating between patients with high and low Ki-67 expression (area under the receiver operating characteristic curves, AUC = 0.748). Multivariate analysis showed that features from the tumor subregion associated with early TTP yielded the highest performance (AUC = 0.807) among the subregions for predicting the Ki-67 status. Among all regions, the tumor area with high PER at a precontrast MR image achieved the highest performance (AUC = 0.722), while the subregion that exhibited the highest overall enhancement rate based on KPC had an AUC of 0.731. These three models based on intratumoral texture analysis significantly (P < 0.01) outperformed the model using features from the whole tumor (AUC = 0.59).Texture analysis of intratumoral heterogeneity has the potential to serve as a valuable

  3. Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit

    2016-06-01

    This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  4. Sex Hormones and Tendon

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2016-01-01

    The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood....... The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet...... has also been linked to a reduced responsiveness to relaxin. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens....

  5. Activational effects of sex hormones on cognition in men.

    Science.gov (United States)

    Ulubaev, A; Lee, D M; Purandare, N; Pendleton, N; Wu, F C W

    2009-11-01

    Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer's. In normally ageing men, these age-related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre- and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility. This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross-sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined. Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis

  6. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

  7. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression.

    Science.gov (United States)

    Nitz, U; Gluz, O; Huober, J; Kreipe, H H; Kates, R E; Hartmann, A; Erber, R; Moustafa, Z; Scholz, M; Lisboa, B; Mohrmann, S; Möbus, V; Augustin, D; Hoffmann, G; Weiss, E; Böhmer, S; Kreienberg, R; Du Bois, A; Sattler, D; Thomssen, C; Kiechle, M; Jänicke, F; Wallwiener, D; Harbeck, N; Kuhn, W

    2014-08-01

    Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1-3 positive lymph nodes (LNs) only. A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥ 20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18-0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1-3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. ClinicalTrials.gov, NCT02115204. © The Author 2014. Published by Oxford University Press on behalf of the European Society for

  8. Thyroid hormone radioimmunoassay

    International Nuclear Information System (INIS)

    Rodriguez, S.; Richmond, M.; Quesada, S.; Lahaman, S.; Ramirez, A.; Herrera, J.F.

    1988-01-01

    The International Atomic Energy Agency (AIEA) is carrying out the ARCAL VIII Program 'Thiroid Hormone Readioimmunoassay'. The Immunoassay Laboratory of INCIENSA is in charge of this program, with the participation of four National Hospital System laboratories, which carried out Thyroxine (T4). Triodothyroxine (T3) and Thyroid Stimulating Hormone (TSH) assays with NETRIA Reagents (North East Thames Region Immunoassay Unit). The variability was shown to be between 9-20 per cent for T4, 12-22 per cent for TSH and 22-36 per cent for T3. The study also evaluated the quality of a tracer (T3-l125 and T4 l125) produced at INCIENSA. In this case the intrassay variability was 8,4 per cent for T3 and 6,8 per cent for T4 in 32 determinations evaluated during 6 months. It was concluded that the T4 and TSH tests but not the T3 test are valid and reproducible when NETRIA Ragents are used. The tracer made at INCIENSA can be used up to 6 weeks after the radioiodination with l125. A successful thyroid-related hormones quality control was defined in Costa Rica by taking advantage of the support of a prestigious international agency, the IAEA. (author). 13 refs, 4 figs

  9. Dairy Consumption in Adolescence and Early Adulthood and Risk of Breast Cancer.

    Science.gov (United States)

    Farvid, Maryam S; Eliassen, A Heather; Cho, Eunyoung; Chen, Wendy Y; Willett, Walter C

    2018-05-01

    Background: Carcinogenic exposure in early life may be critical for subsequent breast cancer risk. Dairy consumption was examined during adolescence and early adulthood in relation to incident breast cancer in the Nurses' Health Study II cohort. Methods: For the analyses of early adulthood dairy consumption, we included 90,503 premenopausal women ages 27 to 44 years in 1991 who reported dairy consumption using a validated food-frequency questionnaire. From 1991 to 2013, 3,191 invasive breast cancer cases were identified. In 1998, 44,264 women recalled adolescent dairy consumption. This subgroup of women was followed up from 1998 to 2013; 1,318 invasive breast cancer cases were identified. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard regression. Results: Adolescent and early adulthood total dairy consumption was not associated with overall breast cancer risk (each serving/day during adolescence, total dairy HR = 1.02, 95% CI, 0.97-1.07; for early adulthood total dairy HR = 1.01, 95% CI, 0.97-1.04), as were intakes of calcium, vitamin D, and lactose. Adolescent consumption of total and high-fat dairy was associated with higher risk of estrogen and progesterone receptor negative (each serving/day: total dairy HR = 1.11, 95% CI, 1.00-1.24; high-fat dairy HR = 1.17, 95% CI, 1.04-1.31). However, higher adolescent high-fat dairy consumption was associated with lower risk of estrogen and progesterone receptor positive tumors (each serving/day HR = 0.91, 95% CI, 0.86-0.97). Conclusions: Our results suggest no overall association between dairy consumption during adolescence or early adulthood and breast cancer risk, but the findings may differ by hormone receptor status of tumors. Impact: Dairy consumption in adolescence or early adulthood may not be a significant predictor of breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 27(5); 575-84. ©2018 AACR . ©2018 American Association for Cancer

  10. Thyroid hormones states and brain development interactions.

    Science.gov (United States)

    Ahmed, Osama M; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M; Ahmed, R G

    2008-04-01

    The action of thyroid hormones (THs) in the brain is strictly regulated, since these hormones play a crucial role in the development and physiological functioning of the central nervous system (CNS). Disorders of the thyroid gland are among the most common endocrine maladies. Therefore, the objective of this study was to identify in broad terms the interactions between thyroid hormone states or actions and brain development. THs regulate the neuronal cytoarchitecture, neuronal growth and synaptogenesis, and their receptors are widely distributed in the CNS. Any deficiency or increase of them (hypo- or hyperthyroidism) during these periods may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, maldevelopment and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions. This could explain the physiological and behavioral changes observed in the animals or human during thyroid dysfunction. It can be hypothesized that the sensitive to the thyroid hormones is not only remarked in the neonatal period but also prior to birth, and THs change during the development may lead to the brain damage if not corrected shortly after the birth. Thus, the hypothesis that neurodevelopmental abnormalities might be related to the thyroid hormones is plausible. Taken together, the alterations of neurotransmitters and disturbance in the GABA, adenosine and pro/antioxidant systems in CNS due to the thyroid dysfunction may retard the neurogenesis and CNS growth and the reverse is true. In general, THs disorder during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems that leads to a multitude of irreversible morphological and biochemical

  11. Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women

    International Nuclear Information System (INIS)

    Pritchard, Kathleen

    2005-01-01

    Endocrine therapy remains important in premenopausal women with hormone receptor positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that it is effective perhaps because of the endocrine ablative effect of chemotherapy. Trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors have estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing recurrence and prolonging survival in the adjuvant setting in premenopausal women. While most of the available data deals with tamoxifen given alone, it appears to have a similar beneficial effect when added to chemotherapy in the premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used in premenopausal women

  12. 99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives

    International Nuclear Information System (INIS)

    Decristoforo, C.; Cholewinski, W.; Donnemiller, E.; Riccabona, G.; Moncayo, R.

    2000-01-01

    [ 111 In-diethylene triamine penta-acetic acid-d-Phe 1 ]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99m Tc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99m Tc-EDDA/HYNIC-TOC were compared with those of 111 In-DTPA-octreotide in six cases, and with those of 111 In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111 In-DTPA-octreotide but faster than that of 111 In-DOTA-TOC, while urinary excretion was lower compared with the 111 In derivatives. Semi-quantitative region of interest analysis showed that 99m Tc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111 In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99m Tc images. We conclude that 99m Tc-EDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111 In-labelled octreotide derivatives. (orig.)

  13. 99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

    Science.gov (United States)

    Decristoforo, C; Mather, S J; Cholewinski, W; Donnemiller, E; Riccabona, G; Moncayo, R

    2000-09-01

    [111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

  14. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  15. Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

    Science.gov (United States)

    Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods. PMID:20808670

  16. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

    DEFF Research Database (Denmark)

    Kølsen-Petersen, Jens Aage; Bendtzen, Klaus; Tønnesen, Else Kirstine

    2008-01-01

    with the other groups (Peffect on the postoperative concentration of selected plasma cytokines and the hormonal stress......BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized...

  17. Thyroid Hormone, Cancer, and Apoptosis.

    Science.gov (United States)

    Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

    2016-06-13

    Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  18. Missed hormonal contraceptives: new recommendations.

    Science.gov (United States)

    Guilbert, Edith; Black, Amanda; Dunn, Sheila; Senikas, Vyta

    2008-11-01

    To provide evidence-based guidance for women and their health care providers on the management of missed or delayed hormonal contraceptive doses in order to prevent unintended pregnancy. Medline, PubMed, and the Cochrane Database were searched for articles published in English, from 1974 to 2007, about hormonal contraceptive methods that are available in Canada and that may be missed or delayed. Relevant publications and position papers from appropriate reproductive health and family planning organizations were also reviewed. The quality of evidence is rated using the criteria developed by the Canadian Task Force on Preventive Health Care. This committee opinion will help health care providers offer clear information to women who have not been adherent in using hormonal contraception with the purpose of preventing unintended pregnancy. The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Instructions for what women should do when they miss hormonal contraception have been complex and women do not understand them correctly. (I) 2. The highest risk of ovulation occurs when the hormone-free interval is prolonged for more than seven days, either by delaying the start of combined hormonal contraceptives or by missing active hormone doses during the first or third weeks of combined oral contraceptives. (II) Ovulation rarely occurs after seven consecutive days of combined oral contraceptive use. (II) RECOMMENDATIONS: 1. Health care providers should give clear, simple instructions, both written and oral, on missed hormonal contraceptive pills as part of contraceptive counselling. (III-A) 2. Health care providers should provide women with telephone/electronic resources for reference in the event of missed or delayed hormonal contraceptives. (III-A) 3. In order to avoid an increased risk of unintended pregnancy, the hormone-free interval should not exceed seven days in combined hormonal contraceptive users. (II-A) 4. Back-up contraception should

  19. Effects of hormone therapy on brain structure

    OpenAIRE

    Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay

    2016-01-01

    Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42?56 years, within 5?36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 ?g/d transdermal 17?-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active ...

  20. Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

    Science.gov (United States)

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

    2010-08-01

    Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia.

    Science.gov (United States)

    Grossmann, Mathis; Ramchand, Sabashini; Milat, Frances; Vincent, Amanda; Lim, Elgene; Kotowicz, Mark A; Hicks, Jill; Teede, Helena

    2018-05-09

    To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor-positive early breast cancer receiving endocrine therapy. Representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing five key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman on tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss, additionally denosumab has proven anti-fracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight-bearing exercise, vitamin D and calcium sufficiency is recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T-score (or Z-scores in women <50 years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualised based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimised by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualised, multidisciplinary approach. Clinical trials are needed to better delineate long-term fracture risks of adjuvant endocrine therapy, and to determine the efficacy of interventions designed to minimise these risks. This article is protected by copyright. All rights reserved. This

  2. Hormone response to bidirectional selection on social behavior.

    Science.gov (United States)

    Amdam, Gro V; Page, Robert E; Fondrk, M Kim; Brent, Colin S

    2010-01-01

    Behavior is a quantitative trait determined by multiple genes. Some of these genes may have effects from early development and onward by influencing hormonal systems that are active during different life-stages leading to complex associations, or suites, of traits. Honey bees (Apis mellifera) have been used extensively in experiments on the genetic and hormonal control of complex social behavior, but the relationships between their early developmental processes and adult behavioral variation are not well understood. Bidirectional selective breeding on social food-storage behavior produced two honey bee strains, each with several sublines, that differ in an associated suite of anatomical, physiological, and behavioral traits found in unselected wild type bees. Using these genotypes, we document strain-specific changes during larval, pupal, and early adult life-stages for the central insect hormones juvenile hormone (JH) and ecdysteroids. Strain differences correlate with variation in female reproductive anatomy (ovary size), which can be influenced by JH during development, and with secretion rates of ecdysteroid from the ovaries of adults. Ovary size was previously assigned to the suite of traits of honey bee food-storage behavior. Our findings support that bidirectional selection on honey bee social behavior acted on pleiotropic gene networks. These networks may bias a bee's adult phenotype by endocrine effects on early developmental processes that regulate variation in reproductive traits. © 2010 Wiley Periodicals, Inc.

  3. The influence of sex hormones on brain lateralization : Research Programme

    NARCIS (Netherlands)

    Beking, Tess; Geuze, Reint; Groothuis, Antonius

    2015-01-01

    Between and within sexes individuals differ in lateralization of brain and behaviour that might affect cognitive performance. There is long standing debate to what extent variation in lateralization is due to variation in early or late exposure to sex hormones. We will use two unique data sets to

  4. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-08-01

    Full Text Available Abstract Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

  5. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

    Science.gov (United States)

    Albain, Kathy S; Barlow, William E; Shak, Steven; Hortobagyi, Gabriel N; Livingston, Robert B; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L; Davidson, Nancy E; Sledge, George W; Winer, Eric P; Hudis, Clifford; Ingle, James N; Perez, Edith A; Pritchard, Kathleen I; Shepherd, Lois; Gralow, Julie R; Yoshizawa, Carl; Allred, D Craig; Osborne, C Kent; Hayes, Daniel F

    2010-01-01

    The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence

  6. GABAA receptor: Positive and negative allosteric modulators.

    Science.gov (United States)

    Olsen, Richard W

    2018-01-31

    gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many potential drugs will be found that share these targets. Although some of these drugs act on proteins involved in synthesis, degradation, and membrane transport of GABA, the GABA receptors Type A (GABA A R) and Type B (GABA B R) are the targets of the great majority of GABAergic drugs. This discovery is due in no small part to Professor Norman Bowery. Whereas the topic of GABA B R is appropriately emphasized in this special issue, Norman Bowery also made many insights into GABA A R pharmacology, the topic of this article. GABA A R are members of the ligand-gated ion channel receptor superfamily, a chloride channel family of a dozen or more heteropentameric subtypes containing 19 possible different subunits. These subtypes show different brain regional and subcellular localization, age-dependent expression, and potential for plastic changes with experience including drug exposure. Not only are GABA A R the targets of agonist depressants and antagonist convulsants, but most GABA A R drugs act at other (allosteric) binding sites on the GABA A R proteins. Some anxiolytic and sedative drugs, like benzodiazepine and related drugs, act on GABA A R subtype-dependent extracellular domain sites. General anesthetics including alcohols and neurosteroids act at GABA A R subunit-interface trans-membrane sites. Ethanol at high anesthetic doses acts on GABA A R subtype-dependent trans-membrane domain sites. Ethanol at low intoxicating doses acts at GABA A R subtype-dependent extracellular domain sites. Thus GABA A R subtypes possess pharmacologically specific receptor binding sites for a large group of different chemical classes of clinically important neuropharmacological agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Effects of thyroid hormones on the heart.

    Science.gov (United States)

    Vargas-Uricoechea, Hernando; Bonelo-Perdomo, Anilsa; Sierra-Torres, Carlos Hernán

    2014-01-01

    Thyroid hormones have a significant impact on heart function, mediated by genomic and non-genomic effects. Consequently, thyroid hormone deficiencies, as well as excesses, are expected to result in profound changes in cardiac function regulation and cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression of phospholamban. Overall, hyperthyroidism is characterized by an increase in resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction. The development of "high-output heart failure" in hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy". On the other hand, in a hypothyroid state, thyroid hormone deficiency results in lower heart rate and weakening of myocardial contraction and relaxation, with prolonged systolic and early diastolic times. Cardiac preload is decreased due to impaired diastolic function. Cardiac afterload is increased, and chronotropic and inotropic functions are reduced. Subclinical thyroid dysfunction is relatively common in patients over 65 years of age. In general, subclinical hypothyroidism increases the risk of coronary heart disease (CHD) mortality and CHD events, but not of total mortality. The risk of CHD mortality and atrial fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher among patients with very low levels of thyrotropin. Finally, medications such as amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff), as well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances, the underlying cause is the high concentration of iodine in this medication. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  8. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  9. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

  10. Effects of intraperitoneal administration of the GABAB receptor positive allosteric modulator 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) on food intake in non-deprived rats.

    Science.gov (United States)

    Ebenezer, Ivor S

    2012-09-05

    γ-Aminobutyric acid-(B) (GABA(B)) receptor positive allosteric modulators (PAMs) act on an allosteric site on the GABA(B) receptor to potentiate the effects of GABA and GABA(B) receptor agonists. It has previously been demonstrated that the GABA(B) receptor agonist baclofen increases food intake in non-deprived rats. The aim of this study was to investigate whether the GABA(B) receptor PAM 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) would (i) increase food intake, and (ii) potentiate the hyperphagic effects of baclofen in rats. In Experiment 1, the effects of intraperitoneal (i.p.) administration of CGP7930 (1, 6 and 12 mg/kg) was investigated on food intake in non-deprived male Wistar rats. The 12 mg/kg dose of CGP7930 significantly increased cumulative food intake 30, 60 and 120 min (PGABA and GABA(B) receptor agonists by allosteric modulation of the GABA(B) receptor. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study.

    Science.gov (United States)

    Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

    2018-01-01

    The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

  12. Hormonotherapy and chemotherapy in hormone refractory prostate cancer

    International Nuclear Information System (INIS)

    Droz, J.

    2004-01-01

    The median survival of patients with metastatic prostate cancer is 3 years, though it is only one year when the tumor is hormone refractory (HRPC). The number of possible problems is great, but the major one is pain. The number of therapeutics is also great. They have only palliative and symptomatic impact. Early hormone suppression in patients with advanced disease may have slight survival impact. Thus, a general scheme of management can be proposed, based on several principles: 1- Early hormone suppression is proposed is metastatic prostate cancer. Hormone suppression is castration or LH-RH agonist. 2- Powerful tools must be used to measure palliative impact: pain and analgesic scales, quality of life evaluation. PSA decrease may only be a surrogate of clinical response evaluation. 3- After first line hormone suppression, indication of further hormone therapy, chemotherapy and radio pharmaceutics is based only on symptomatic progression. It is not based on tumor progression as measured by PSA increase or metastasis evolution, because it is well established that, till now, treatment has only palliative effect. 4- Management of local problems (urinary obstruction, fracture, nerve compression) must be done depending on the situation. 4- Patients must be clearly informed of the palliative end-points, of the therapeutic tools, of the current side effects and goals of treatments. The strategy must be prospectively explained at the early beginning of treatment. Chemotherapy has become a standard treatment in HRPC because it has shown palliative improvement (Mitoxantrone studies), and more recently survival improvement (Docetaxel studies). However new drugs are under development. It will be focussed on drugs acting on EGF-receptor, endothelin-A, proteasome and V EGF. Practical management of HRPC will be discussed

  13. Growth hormone therapy: emerging dilemmas.

    Science.gov (United States)

    Laron, Zvi

    2011-06-01

    The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long-term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects.

  14. Interactions between hormones and epilepsy.

    Science.gov (United States)

    Taubøll, Erik; Sveberg, Line; Svalheim, Sigrid

    2015-05-01

    There is a complex, bidirectional interdependence between sex steroid hormones and epilepsy; hormones affect seizures, while seizures affect hormones thereby disturbing reproductive endocrine function. Both female and male sex steroid hormones influence brain excitability. For the female sex steroid hormones, progesterone and its metabolites are anticonvulsant, while estrogens are mainly proconvulsant. The monthly fluctuations in hormone levels of estrogen and progesterone are the basis for catamenial epilepsy described elsewhere in this issue. Androgens are mainly anticonvulsant, but the effects are more varied, probably because of its metabolism to, among others, estradiol. The mechanisms for the effects of sex steroid hormones on brain excitability are related to both classical, intracellularly mediated effects, and non-classical membrane effects due to binding to membrane receptors. The latter are considered the most important in relation to epilepsy. The different sex steroids can also be further metabolized within the brain to different neurosteroids, which are even more potent with regard to their effect on excitability. Estrogens potentiate glutamate responses, primarily by potentiating NMDA receptor activity, but also by affecting GABA-ergic mechanisms and altering brain morphology by increasing dendritic spine density. Progesterone and its main metabolite 5α-pregnan-3α-ol-20-one (3α-5α-THP) act mainly to enhance postsynaptic GABA-ergic activity, while androgens enhance GABA-activated currents. Seizures and epileptic discharges also affect sex steroid hormones. There are close anatomical connections between the temporolimbic system and the hypothalamus controlling the endocrine system. Several studies have shown that epileptic activity, especially mediated through the amygdala, alters reproductive function, including reduced ovarian cyclicity in females and altered sex steroid hormone levels in both genders. Furthermore, there is an asymmetric

  15. contribution of growth hormone-releasing hormone and

    African Journals Online (AJOL)

    The strategy used was to stimulate GH secretion in 8 young ... treatment with two oral doses of 50 mg atenolol (to inhibit .... had normal baseline thyroid-stimulating hormone (TSH) ..... production rate of 14% per decade has been documented.'".

  16. Sex Hormones and Ischemic Stroke

    DEFF Research Database (Denmark)

    Holmegard, Haya N; Nordestgaard, Børge G; Jensen, Gorm B

    2016-01-01

    CONTEXT AND OBJECTIVE: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. DESIGN, SETTING, AND PARTICIPANTS: Adult men (n...... = 4615) and women (n = 4724) with measurements of endogenous sex hormones during the 1981-1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through...

  17. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    Science.gov (United States)

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

  18. Sex hormone activity in alcohol addiction: integrating organizational and activational effects.

    Science.gov (United States)

    Lenz, Bernd; Müller, Christian P; Stoessel, Christina; Sperling, Wolfgang; Biermann, Teresa; Hillemacher, Thomas; Bleich, Stefan; Kornhuber, Johannes

    2012-01-01

    There are well-known sex differences in the epidemiology and etiopathology of alcohol dependence. Male gender is a crucial risk factor for the onset of alcohol addiction. A directly modifying role of testosterone in alcohol addiction-related behavior is well established. Sex hormones exert both permanent (organizational) and transient (activational) effects on the human brain. The sensitive period for these effects lasts throughout life. In this article, we present a novel early sex hormone activity model of alcohol addiction. We propose that early exposure to sex hormones triggers structural (organizational) neuroadaptations. These neuroadaptations affect cellular and behavioral responses to adult sex hormones, sensitize the brain's reward system to the reinforcing properties of alcohol and modulate alcohol addictive behavior later in life. This review outlines clinical findings related to the early sex hormone activity model of alcohol addiction (handedness, the second-to-fourth-finger length ratio, and the androgen receptor and aromatase) and includes clinical and preclinical literature regarding the activational effects of sex hormones in alcohol drinking behavior. Furthermore, we discuss the role of the hypothalamic-pituitary-adrenal and -gonadal axes and the opioid system in mediating the relationship between sex hormone activity and alcohol dependence. We conclude that a combination of exposure to sex hormones in utero and during early development contributes to the risk of alcohol addiction later in life. The early sex hormone activity model of alcohol addiction may prove to be a valuable tool in the development of preventive and therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. HORMONAL TREATMENT IN UROGYNECOLOGY

    Directory of Open Access Journals (Sweden)

    Adolf Lukanović

    2018-02-01

    Full Text Available Background. Hormonal treatment in urogynecology is based on the knowledge, that urinary and reproductive tracts have common embriologic origin and are also linked anatomically and functionally. Both systems are functioning and changing due to sex steroids influence. Decreased estrogen concentrations are connected to metabolic and trophic changes in all organs with estrogen receptors, i.e. also in urogenital tract. Atrophy of urogenital system in postmenopause is a common causative factor for stress urinary incontinence (SUI and urge incontinence (UUI. In both estrogen replacement treatment have been introduced, but meta-analyses of the available literature indicate that estrogen therapy is effective only if given vaginaly. Recurrent urinary tract infections (RUTI occur in postmenopause often as a consequence of structural changes in urinary and reproductive tract to lowered immune protection and colonization with eneterobacteria. In RUTI too, estrogen replacement treatment have been used with the results similar to those with SUI and UUI. Effectiveness of estrogen treatment was evident only in topically applied vaginaly, while oral administration has the same effectiveness as placebo. Conclusions. Structural changes in urogenital tract in postmenopause are the results of estrogen depletion. Estrogen replacement is effective in cases of SUI, UUI and RUTI if it is applied topicaly, the efffect being influenced by the type of estrogen used and duration of treatment.

  20. Measurement of the incretin hormones

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette

    2015-01-01

    The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrat......The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma...... concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological...

  1. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  2. Network identification of hormonal regulation.

    Directory of Open Access Journals (Sweden)

    Daniel J Vis

    Full Text Available Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for detecting regulatory relations between hormones. This is demonstrated with a cohort of obese women, who underwent blood sampling at 10 minute intervals for 24-hours. The cohort was treated with bromocriptine in an attempt to clarify how hormone relations change by treatment. The detected regulatory relations are summarized in a network graph and treatment-induced changes in the relations are determined. The proposed method identifies many relations, including well-known ones. Ultimately, the method provides ways to improve the description and understanding of normal hormonal relations and deviations caused by disease or treatment.

  3. Growth Hormone Deficiency in Children

    Science.gov (United States)

    ... your child if you see signs of poor self-esteem or sadness that could be related to being ... December 2011 The Hormone Health Network offers free, online resources based on the most advanced clinical and ...

  4. A possible role for reproductive hormones in newborn boys

    DEFF Research Database (Denmark)

    Main, K M; Schmidt, I M; Skakkebaek, N E

    2000-01-01

    Healthy boys have a considerable production of reproductive hormones during the first postnatal months, the biological significance of which is poorly understood. We report on cases of male infants with hypogonadism (hypogonadotropic hypogonadism, n = 1; panhypopituitarism, n = 2) who showed lack...... of penile growth and involution of the scrotum. In two boys, diagnoses were obtained in early infancy and hormonal measurements at 3-4 months of age showed serum testosterone levels below detection limits in both low inhibin B (37 and 199 pg/mL, respectively; normal range, 193-563 pg/mL) and low......RH. All cases required hormonal treatment with testosterone, administered as suppositories in daily doses between 1 and 5 mg, which reintroduced male genital development. Our observations suggest that normal phallic and scrotal development in humans is dependent on intact testosterone secretion during...

  5. Breast Milk Hormones and Regulation of Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Francesco Savino

    2011-01-01

    Full Text Available Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.

  6. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  7. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with 18F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients.

    Science.gov (United States)

    Lemarignier, Charles; Martineau, Antoine; Teixeira, Luis; Vercellino, Laetitia; Espié, Marc; Merlet, Pascal; Groheux, David

    2017-07-01

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an 18 F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV max and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV max and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV max and TLG were able to predict response to NAC, TFs failed.

  8. Clinicopathologic Characteristics of Oestrogen Receptor-Positive/Progesterone Receptor-Negative/Her2-Negative Breast Cancer According to a Novel Definition of Negative Progesterone Receptor Status: A Large Population-Based Study from China.

    Directory of Open Access Journals (Sweden)

    An-qi Li

    Full Text Available A lack of progesterone receptor (PgR expression in oestrogen receptor-positive (ER+ tumours is associated with worse survival. PgR status is usually defined as positive or negative using 1% positive nuclei as a cut-off point. In this study, we aimed to assess the clinicopathologic characteristics of ER+/PgR-/HER2- tumours by comparing them with ER+/PgR+/HER2- tumours using a PgR cut-off point of 20% as a divisive criterion.We analysed 1,522 patients with primary breast cancer who had undergone surgery at the Cancer Center of Fudan University between 2012 and 2014. Age, grade, tumour size, lymph node status and lymphovascular invasion were assessed. Multinomial logistic regression, linear regression and chi-square test models were applied to assess associations between ER, PR and clinical features.ER+/PgR-/HER2- tumours showed poorer clinicopathologic characteristics relative to ER+/PgR+/HER2- tumours using a PgR threshold of 20% instead of 1%. The clinicopathologic characteristics did not differ between tumours with purely negative PgR expression and tumours with a PgR percentage ranging from 1% to 19%. The prognostic significance of PR expression appeared more pronounced in patients under a high Ki-67 status than those under a low Ki-67 status.Based on these findings, we propose the use of a novel threshold of 20% to define PgR status. Nevertheless, the impact of this new criterion on patient management and clinical treatment requires additional study.

  9. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  10. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  11. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K W; Choe, K O; Park, C Y; Lee, H; Son, H Y; Huh, K B; Ryu, K J [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  12. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  13. Growth Hormone and Endocrinopathies

    International Nuclear Information System (INIS)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J.

    1979-01-01

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  14. Gastrointestinal hormone research - with a Scandinavian annotation

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2015-01-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones...... as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions...

  15. Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

    OpenAIRE

    Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha; Vaidya, Vidita A.

    2011-01-01

    Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and...

  16. Contribution of stress and sex hormones to memory encoding.

    Science.gov (United States)

    Merz, Christian J

    2017-08-01

    Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC) affect sex hormone levels, stress responses, and memory processes critically involved in the pathogenesis of mental disorders. To characterize the interaction of sex and stress hormones on memory encoding, 30 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women were exposed to either a stress (socially evaluated cold-pressor test) or a control condition prior to memory encoding and immediate recall of neutral, positive, and negative words. On the next day, delayed free and cued recall was tested. Sex hormone levels verified distinct estradiol, progesterone, and testosterone levels between groups. Stress increased blood pressure, cortisol concentrations, and ratings of stress appraisal in all four groups as well as cued recall performance of negative words in men. Stress exposure in OC women led to a blunted cortisol response and rather enhanced cued recall of neutral words. Thus, pre-encoding stress facilitated emotional cued recall performance in men only, but not women with different sex hormone statuses pointing to the pivotal role of circulating sex hormones in modulation of learning and memory processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. What is the current status of ovarian suppression/ablation in women with premenopausal early-stage breast cancer?

    Science.gov (United States)

    Higgins, Michaela J; Davidson, Nancy E

    2009-01-01

    The role of ovarian suppression/ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer has been evolving for more than a century. It is clear that OS/OA is an effective adjuvant therapy for these women, but despite numerous studies enrolling thousands of women, many unanswered questions remain. In particular, a major question is whether additional benefit is gained with combination treatment comprising luteinizing hormone-releasing hormone (LH-RH) agonists and tamoxifen over tamoxifen alone. Ongoing trials also are assessing the coupling of aromatase inhibitors (traditionally contraindicated in these patients because of paradoxic stimulation of estrogen production) and LH-RH agonists. Any potential disease-free or overall survival advantage of combination treatment must be balanced against a possible increase in adverse effects and impairment of quality of life. This review focuses on new data on how to incorporate OS/OA into the rational treatment of this challenging patient population.

  18. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    Science.gov (United States)

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

    2016-09-02

    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

  19. Physiological Regulation of Gut Peptide Hormone (PYY) Levels by Age, Sex, Hormonal and Nutritional Status in Rats

    International Nuclear Information System (INIS)

    Hebashy, M.I.A.; Mazen, G.M.A.

    2007-01-01

    Peptide YY hormone (PYY) was recently appreciated as an important gut hormonal regulator of appetite. PYY is produced by the gut and released into the circulation after food intake and is found to decrease appetite. The main form of PYY, both stored and circulated, is PYY(3-36), the N-terminal truncated form of the full length peptide so, peripheral injections of PYY(3-36) in rats inhibit food intake in experimental animals as well as in lean and obese human subjects. Also, this hormone has been suggested to be an attractive therapeutic option for obesity. PYY levels are influenced by age and the highest hormone level is achieved in early postnatal life (day 30) and is decreased thereafter. PYY levels were also dependent on thyroid hormone status and being decreased in hyperthyroid rats. The PYY levels observed in acute and chronic food restricted rats indicated that, in situations of decreased energy intake, the lower PYY levels could serve to regulate central pathways and facilitate food intake. Contrary, in pregnant rats, PYY levels were enhanced at late gestation. The aim of this study was to assess the influence of age, sex, thyroid status, pregnancy and food restriction on PYY levels in rats. The underling mechanisms through which PYY levels alternated as a result of sex, age, pregnancy, thyroidal and nutritional status were discussed in the light of recent research outcomes

  20. Thyroid hormones: Possible roles in epilepsy pathology.

    Science.gov (United States)

    Tamijani, Seyedeh Masoumeh Seyedhoseini; Karimi, Benyamin; Amini, Elham; Golpich, Mojtaba; Dargahi, Leila; Ali, Raymond Azman; Ibrahim, Norlinah Mohamed; Mohamed, Zahurin; Ghasemi, Rasoul; Ahmadiani, Abolhassan

    2015-09-01

    Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort.

    Science.gov (United States)

    Emaus, Marleen J; Peeters, Petra H M; Bakker, Marije F; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Romieu, Isabelle; Ferrari, Pietro; Dossus, Laure; Boutron-Ruault, Marie Christine; Baglietto, Laura; Fortner, Renée T; Kaaks, Rudolf; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Polidoro, Silvia; Skeie, Guri; Lund, Eiliv; Weiderpass, Elisabete; Quirós, J Ramón; Travier, Noémie; Sánchez, María-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Dorronsoro, Miren; Winkvist, Anna; Wennberg, Maria; Bueno-de-Mesquita, H Bas; Khaw, Kay-Tee; Travis, Ruth C; Key, Timothy J; Aune, Dagfinn; Gunter, Marc; Riboli, Elio; van Gils, Carla H

    2016-01-01

    The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk. This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk. A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors. After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk. This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk. © 2016 American Society for Nutrition.

  2. Hormonal Approaches to Male contraception

    Science.gov (United States)

    Wang, Christina; Swerdloff, Ronald S.

    2010-01-01

    Purpose of review Condoms and vasectomy are male controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be safe. Recent Findings The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or non-government organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and non-governmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment. Summary Male hormonal contraception is efficacious, reversible and safe for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic actions. PMID:20808223

  3. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  4. Radioimmunological and clinical studies with luteinizing hormone releasing hormone (LRH)

    International Nuclear Information System (INIS)

    Dahlen, H.G.

    1986-01-01

    Radioimmunoassay for Luteinizing Hormone Releasing Hormone (LRH) has been established, tested and applied. Optimal conditions for the performance with regards to incubation time, incubation temperature, concentration of antiserum and radiolabelled LRH have been established. The specificity of the LRH immunoassay was investigated. Problems with direct measurement of LRH in plasmas of radioimmunoassay are encountered. The LRH distribution in various tissues of the rat are investigated. By means of a system for continuous monitoring of LH and FSH in women the lowest effective dose of LRH causing a significant release of LH and FSH could be established. (Auth.)

  5. Decreased levels of circulating sex hormones as a biomarker of lung ...

    African Journals Online (AJOL)

    Background: An early differentiation of malignant from benign solitary pulmonary nodules (SPNs) is essential for management and prognosis of lung cancer. Objectives: Here we investigated whether measurement of circulating sex hormones could be useful for an early detection of malignancy among patients with SPNs.

  6. Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Munch-Andersen, Thor

    2009-01-01

    Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor...... of glucose metabolism and metabolic risk during puberty....

  7. Clinical relevance of hormone receptors in breast cancer diagnosis

    International Nuclear Information System (INIS)

    Knapstein, P.

    1981-01-01

    After an outline of the epidemiology of breast cancer, risk factors such as age, family history, ethnic factors, environmental effects, pregnancy, and hormonal factors are presented. The most efficient methods of early detection are palpation, mammography, and xeroradiography, although repeated mammography involves a risk of tumour induction. Further methods not suited for screeening are puncture cytology and thermography, of which the latter often yields wrong findings. New ways of mass screening may be found in sonography and microwave thermography. (MG) [de

  8. Some theoretical aspects of hormone receptor determination

    International Nuclear Information System (INIS)

    Sluiter, W.J.

    1981-01-01

    Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

  9. Advances in male hormonal contraception.

    Science.gov (United States)

    Costantino, Antonietta; Gava, Giulia; Berra, Marta; Meriggiola Maria, Cristina

    2014-11-01

    Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.

  10. Advances in male hormonal contraception

    Directory of Open Access Journals (Sweden)

    Costantino Antonietta

    2014-01-01

    Full Text Available Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.

  11. Hormonal interaction in diabetic pregnancy

    International Nuclear Information System (INIS)

    Hafiez, A.R.A.; Abdel-Hafez, M.A.; Osman, E.A.; Ibrahim, M.S.

    1984-01-01

    Serum glucose, human placental lactogen (HPL), prolactin (PRL), estradiol (E 2 ), progesterone (P), cortisol and human growth hormone (HGH) were determined in nondiabetic (19 cases) and diabetic (19 cases) pregnant women during the 32nd and 36th week of gestation. Significant elevation of HPL, PRL, HGH and cortisol was found in the diabetic pregnant women during the 32nd week while E 2 and P were not significantly changed from the corresponding levels in the nondiabetic group. One can conclude that the changes in the hormonal pattern during gestation may induce carbohydrate intolerance observed in diabetic pregnancies. (author)

  12. Hormonal contraception, thrombosis and age

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind

    2014-01-01

    : First choice in women below 35 years should be a combined low-risk pill, that is, with a second-generation progestin, with the lowest compliable dose of estrogen. Young women with risk factors of thrombosis such as age above 35 years, genetic predispositions, adiposity, polycystic ovary syndrome......INTRODUCTION: This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages. AREAS COVERED: Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased...

  13. Hormonal Changes and Sexual Dysfunction.

    Science.gov (United States)

    Zhou, Eric S; Frederick, Natasha N; Bober, Sharon L

    2017-11-01

    Sexual dysfunction is a common concern for many patients with cancer after treatment. Hormonal changes as a result of cancer-directed therapy can affect both male and female sexual health. This has the potential to significantly impact patients' quality of life, but is underreported and undertreated in the oncology setting. This review discusses commonly reported sexual issues and the role that hormonal changes play in this dysfunction. Although medical and psychosocial intervention strategies exist, there is a clear need for further research to formally develop programming that can assist people whose sexual health has been impacted by cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Luteinizing hormone in testicular descent

    DEFF Research Database (Denmark)

    Toppari, Jorma; Kaleva, Marko M; Virtanen, Helena E

    2007-01-01

    alone is not sufficient for normal testicular descent. The regulation of androgen production is influenced both by placental human chorionic gonadotropin (hCG) and pituitary luteinizing hormone (LH). There is evidence that the longer pregnancy continues, the more important role pituitary LH may have....... Insulin-like hormone-3 (INSL3) is suggested to be the main regulator of gubernacular development and therefore an apparent regulator of testicular descent. INSL3 production is also related to LH, and reduced INSL3 action is a possible cause for cryptorchidism. Cryptorchid boys have normal testosterone...

  15. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    OpenAIRE

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

  16. Hormonal responses to resistance exercise during different menstrual cycle states.

    Science.gov (United States)

    Nakamura, Yuki; Aizawa, Katsuji; Imai, Tomoko; Kono, Ichiro; Mesaki, Noboru

    2011-06-01

    To investigate the effect of menstrual cycle states on ovarian and anabolic hormonal responses to acute resistance exercise in young women. Eight healthy women (eumenorrhea; EM) and eight women with menstrual disorders including oligomenorrhea and amenorrhea (OAM) participated in this study. The EM group performed acute resistance exercises during the early follicular (EF) and midluteal (ML) phases, and the OAM group performed the same exercises. All subjects performed three sets each of lat pull-downs, leg curls, bench presses, leg extensions, and squats at 75%-80% of one-repetition maximum with a 1-min rest between sets. Blood samples were obtained before exercise, immediately after, 30 min after, and 60 min after the exercise. In the EM group, resting serum levels of estradiol and progesterone in the ML phase were higher than those in the EF phase and higher than those in the OAM group. Serum estradiol and progesterone in the ML phase increased after the exercise but did not change in the EF phase or in the OAM group. In contrast, resting levels of testosterone in the OAM group were higher than those in both the ML and EF phases of the EM group. After the exercise, serum growth hormone increased in both the ML and EF phases but did not change in the OAM group. The responses of anabolic hormones to acute resistance exercise are different among the menstrual cycle states in young women. Women with menstrual disturbances with low estradiol and progesterone serum levels have an attenuated anabolic hormone response to acute resistance exercise, suggesting that menstrual disorders accompanying low ovarian hormone levels may affect exercise-induced change in anabolic hormones in women.

  17. Etiology of growth hormone deficiency in children and adolescents

    Directory of Open Access Journals (Sweden)

    Mitrović Katarina

    2013-01-01

    Full Text Available Introduction. Growth hormone deficiency (GHD can be isolated or associated with deficiency of other pituitary gland hormones. According to age at diagnosis, causes of GHD are divided into congenital or acquired, and according to etiology into recognized and unknown. Objective. We analyzed etiology and prevalence of GHD, demographic data at birth, age, body height (BH and bone age at diagnosis as well as the frequency of other pituitary hormone deficiencies. Methods. The study involved 164 patients (109 male. The main criterion for the diagnosis of GHD was inadequate response of GH after two stimulation tests. The patients were classified into three groups: idiopathic, congenital and acquired GHD. Results. Idiopathic GHD was confirmed in 57.9% of patients, congenital in 11.6% and acquired in 30.5%. The mean age at diagnosis of GHD was 10.1±4.5 years. The patients with congenital GHD had most severe growth retardation (-3.4±1.4 SDS, while the patients with idiopathic GHD showed most prominent bone delay (-3.6±2.3 SDS. The prevalence of multiple pituitary hormone deficiency was 56.1%, in the group with congenital GHD 73.7%, acquired GHD 54.0% and idiopathic GHD 53.7%. The frequency of thyrotropin deficiency ranged from 88.2-100%, of adrenocorticotrophin 57.1-68.8% and of gonadotrophins deficiency 57.1- 63.0%, while deficiency of antidiuretic hormone was 2.0-25.0%. Conclusion. Although regular BH measurements enable early recognition of growth retardation, patients’ mean age and degree of growth retardation indicate that GHD is still diagnosed relatively late. A high incidence of other pituitary hormone deficiencies requires a detailed investigation of the etiology of disorders and evaluation of all pituitary functions in each child with confirmed GHD.

  18. Hormonal regulation of lipid metabolism in developing coho salmon, Oncorhynchus kisutch

    International Nuclear Information System (INIS)

    Sheridan, M.A.

    1985-01-01

    Lipid metabolism in juvenile coho salmon is characterized, and adaptive changes in lipid mobilization are described in relation to development and hormonal influences. The rates of lipogenesis and lipolysis were determined in selected tissues of juvenile salmon during the period of seawater preadaptive development (smoltification). Neutral lipid (sterol) and fatty acid synthesis in the liver and mesenteric fat was measured by tritium incorporation. Fatty acid synthesis in the liver and mesenteric fat decreased by 88% and 81%, respectively, between late February (parr) and early June (smolt). To assess the role of hormones in smoltification-associated lipid depletion, growth hormone, prolactin, thyroxin and cortisol were administered in vivo early in development (parr) to determine if any of these factors could initiate the metabolic responses normally seen later in development (smolt). Growth hormone stimulated lipid mobilization from coho salmon parr. Prolactin strongly stimulated lipid mobilization in coho parr. Thyroxin and cortisol also stimulated lipid mobilization for coho salmon parr. The direct effect of hormones was studied by in vitro pH-stat incubation of liver slices. These data suggest that norepinephrine stimulates fatty acid release via β-adrenergic pathways. Somatostatin and its partial analogue from the fish caudal neurosecretory system, urotensin II, also affect lipid mobilization. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that the regulation of lipid metabolism in salmon involves both long-acting and short-acting hormonal agents

  19. Anti-mullerian hormon level and polycystic ovarian syndrome diagnosis

    Directory of Open Access Journals (Sweden)

    Shahrzad Zadehmodarres

    2015-03-01

    Full Text Available Background: Polycystic ovarian syndrome (PCOS is a common endocrinopathy that accompanied with long term complications. The early diagnosis of this syndrome can prevent it. Objective: The aim was to determine the role of anti-mullerian hormon (AMH in PCOS diagnosis and to find cut off level of it. Materials and Methods: In this cross sectional study, 117 women between 20-40 years old were participated in two groups: 60 PCOS women (based on Rotterdam criteria consensus as the case group and 57 normal ovulatory women as the control group. In day 2-4 of cycle, transvaginal sonography was performed and serum hormonal level of AMH, luteinizing hormone (LH, follicle stimulating hormone (FSH, estradiol (E2, testosterone, fasting blood sugar (FBS, thyroid stimulating hormone (TSH, and prolactin (PRL were measured in all of participants. For all of them score of hirsutism (base on Freeman-Galloway scoring was determined. Results: There were statistically significant in irregular pattern of menstruation, AMH and FSH level, and presence of hirsutism between two groups. But regarding mean of age, body mass index, plasma level of PRL, TSH, LH, Testosterone, FBS, and E2 differences were not significant. Construction by ROC curve present 3.15 ng/ml as AMH cut off with 70.37% sensitivity and 77.36% specificity in order to PCOS diagnosis. Conclusion: AMH with cut off level of 3.15 ng/ml with sensitivity 70.37% and specificity 77.36% could use for early diagnosis of PCOS patients.

  20. Interactions between the thyroid hormones and the hormones of the growth hormone axis.

    Science.gov (United States)

    Laron, Zvi

    2003-12-01

    The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

  1. Network identification of hormonal regulation

    NARCIS (Netherlands)

    Vis, D.J.; Westerhuis, J.A.; Hoefsloot, H.C.J.; Roelfsema, F.; Greef, J. van der; Hendriks, M.M.W.B.; Smilde, A.K.

    2014-01-01

    Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for

  2. Hormonal signaling in plant immunity

    NARCIS (Netherlands)

    Caarls, L.

    2016-01-01

    Insect hervivores and pathogens are a major problem in agriculture and therefore, control of these pests and diseases is essential. For this, understanding the plant immune response can be instrumental. The plant hormones salicylic acid (SA) and jasmonic acid (JA) play an essential role in defense

  3. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  4. Incretin hormones--an update

    DEFF Research Database (Denmark)

    Holst, J J; Orskov, C

    2001-01-01

    important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP, previously known as gastric inhibitory polypeptide) and glucagon-like peptide-1 (GLP-1) from the upper and lower small intestinal mucosa, respectively. It has been shown that interference with the incretin function causes...

  5. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

  6. Quo vadis plant hormone analysis?

    Czech Academy of Sciences Publication Activity Database

    Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, P.; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

    2014-01-01

    Roč. 240, č. 1 (2014), s. 55-76 ISSN 0032-0935 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Plant hormones * Extraction * Mass spectrometr Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.263, year: 2014

  7. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...

  8. Hormones and growth factors in breast cancer

    African Journals Online (AJOL)

    Herman-Giddens M. Condylomata acuminata in children and sexual abuse. Genitourin ..... accommodated reasonably easily in the outline of hormone action referred to ... tumours may still respond to hormone manipulation with another type of ...

  9. Follicle-stimulating hormone (FSH) blood test

    Science.gov (United States)

    ... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

  10. Pituitary-hormone secretion by thyrotropinomas

    NARCIS (Netherlands)

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

    2009-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading

  11. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on the body. It stimulates the ...

  12. Steroid hormone signaling during development has a latent effect on adult male sexual behavior in the butterfly Bicyclus anynana.

    Science.gov (United States)

    Bear, Ashley; Prudic, Kathleen L; Monteiro, Antónia

    2017-01-01

    It is well established that steroid hormones regulate sexual behavior in vertebrates via organizational and activational effects. However, whether the organizational/activational paradigm applies more broadly to the sexual behavior of other animals such as insects is not well established. Here we describe the hormonal regulation of a sexual behavior in the seasonally polyphenic butterfly Bicyclus anynana is consistent with the characteristics of an organizational effect. By measuring hormone titer levels, quantifying hormone receptor gene expression in the brain, and performing hormone manipulations, we demonstrate steroid hormone signaling early in pupal development has a latent effect on adult male sexual behavior in B. anynana. These findings suggest the organizational/activational paradigm may be more highly conserved across animal taxa than previously thought.

  13. Headaches and Hormones: What's the Connection?

    Science.gov (United States)

    Headaches and hormones: What's the connection? Being female has some real health advantages, but not when it comes to headaches — particularly ... a relationship between headaches and hormonal changes. The hormones estrogen (ES-truh-jen) and progesterone (pro-JES- ...

  14. Peptide Hormones in the Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  15. Parathyroid hormone-related protein blood test

    Science.gov (United States)

    ... ency/article/003691.htm Parathyroid hormone-related protein blood test To use the sharing features on this page, ... measures the level of a hormone in the blood, called parathyroid hormone-related protein. How the Test is Performed A blood sample is needed . How ...

  16. Thyroid hormone signaling in the hypothalamus

    NARCIS (Netherlands)

    Alkemade, Anneke; Visser, Theo J.; Fliers, Eric

    2008-01-01

    PURPOSE OF REVIEW: Proper thyroid hormone signaling is essential for brain development and adult brain function. Signaling can be disrupted at many levels due to altered thyroid hormone secretion, conversion or thyroid hormone receptor binding. RECENT FINDINGS: Mutated genes involved in thyroid

  17. Obesity, growth hormone and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby

    2009-01-01

    Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk...

  18. Correlations Between Seminal Plasma Hormones and Sperm ...

    African Journals Online (AJOL)

    Context: There is a complex relationship between seminal plasma hormone levels and infertility in men. Previous studies had shown no specific pattern in the serum or seminal plasma hormone profiles of men with infertility and it is debatable whether there is a need to perform routine seminal hormone assays in the ...

  19. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

  20. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy

    DEFF Research Database (Denmark)

    Petersen, Jesper Friis; Bergholt, T; Nielsen, A. K.

    2014-01-01

    Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed...... pregnancies aged 15-49 during the period of 1995-2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early...... terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives...

  1. The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

    Science.gov (United States)

    Root, A W; Shulman, D; Root, J; Diamond, F

    1986-01-01

    Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

  2. Influence of gonadotropin-releasing hormone and timing of insemination relative to estrus on pregnancy rates of dairy cattle at first service.

    Science.gov (United States)

    Mee, M O; Stevenson, J S; Scoby, R K; Folman, Y

    1990-06-01

    The objective was to determine the influence of gonadotropin-releasing hormone on pregnancy rates of dairy cattle at first services, when both the timing of hormone injection and insemination were altered relative to the onset of estrus. Cows (n = 325) were assigned randomly to six groups making up a 2 X 2 X 2 incomplete factorial experiment; dose of GnRH (100 micrograms versus saline), timing [1 h (early) or 12 to 16 h (late) after first detected estrus] of AI, and timing of hormone injection (early versus late) were the three main effects. Cows were observed for estrus 4 times daily. Treatments and resulting pregnancy rates were: 1) hormone injection early plus AI early (35%), 2) hormone injection late plus AI early (34%), 3) saline injection early plus AI early (30%), 4) hormone injection late plus AI late (30%), 5) hormone injection early plus AI late (46%), and 6) saline injection late plus AI late (43%). Pregnancy rate in the first four groups (32%) was less than that in the latter two groups (44%). Concentrations of LH in serum were greater for cows given hormone or saline injections in early estrus than for cows injected with either hormone of saline during late estrus. Concentrations of LH in serum 2 h after GnRH were elevated above those of controls, whether GnRH was injected during early or late estrus. Neither concentrations of LH during estrus nor concentrations of progesterone 8 to 14 d after estrus explained the possible antifertility effect of GnRH given during late estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Obesity and hormonal contraceptive efficacy.

    Science.gov (United States)

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  4. Progress of measurement of hormones

    International Nuclear Information System (INIS)

    Ohsawa, Nakaaki

    1977-01-01

    Description was made as to an outline of the theory of radioreceptor assay (RRA) in which hormone receptor was used as specific binding protein, as same as the theory of RIA, and as to its practical use. Meaning of RRA for measurement of hormones in consideration of the site of immunological and biological activation and meaning of difference in measurement values between this method and in RIA in the same materials, were mentioned, and effectiveness of use of this method together with RIA was described. Detection of receptor site, analysis of binding specificity, and numerical calculation were mentioned as receptor analysis by this method. As practical use of these functions, arrangement mechanism of receptor, and analysis of abnormality were mentioned. Especially, analysis of testicular feminization syndrome, insulinresistenter diabetes, hyperthyroidism, and myasthenia gravis, and relationship between these diseases and autoimmune diseases were described, and clinical meaning of this method in internal medicine and surgery was mentioned. (Kanao, N.)

  5. Patient communication in hormone therapy.

    Science.gov (United States)

    Schnare, S M

    2001-01-01

    Common regimens of HRT therapy are reviewed, including common routes of hormone administration. Inconsistent patterns of HRT use are discussed, including the reasons women most often give for discontinuing hormone therapies. Specific issues related to misperceptions and fears regarding HRT are clarified, and specific, focused patient education formats are discussed to address women's common concerns about HRT. Obstacles to HRT use are elucidated, with suggestions for clinicians about how to communicate more effectively with women: clinicians must focus on emotional and physical aspects of HRT choices and tailor therapies to the individual patient. Discussing frankly the very serious concerns of women regarding the association between lobular breast cancer and endometrial cancer is important; discussing and preparing women for possible side effects helps patients cope better if and when side effects occur. Finally, offering a wide variety of HRT therapies provides women with a broader choice if an initial regimen is unsuccessful.

  6. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    Fromageot, P.; Pradelles, P.; Morgat, J.L.; Levine, H.

    1976-01-01

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3 H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  7. Evaluation Of Hormone Profile And Dexa Values in Premenopausal, Perimenopausal and Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Esra Esen

    2005-09-01

    Full Text Available This study was carried out in 130 women, between 44-55 ages, admitted to outpatient clinic of Physical Medicine and Rehabilitation Department of Trakya University Medical Faculty in order to make. comparison of hormone profile and DEXA values of premenopausal, perimenopausal, and postmenopausal women . Three groups were allocated according to climacteric symptoms and menopause condition. Premenopausal group consisted of women who had regular menstruation and did not have any climacteric symptoms , perimenopausal group consisted of women who had menstruation disorder and climacteric symptoms within one year and postmenopausal group consisted of women who had last menstruation within more than one year and less than 5 years. Women who had prior osteoporosis diognosis and treatment, hormone replacement therapy, surgical menopause and menopause duration more than 5 years were excluded from the study. Age, body weight ,height, hormone profile including estradiol (E2, progesterone (P, follicule stimulating hormone (FSH, luteinizing hormone (LH, parathyroid hormone (PTH, thyroid hormones (T3, T4, thyroid stimulating hormone (TSH and DEXA values representing bone mineral density (BMD of both groups were evaluated. In peri and postmenopausal groups, E2, P, FSH and LH values were significantly lower, while there was no significant difference for PTH and thyroid hormone levels comparing to premenopausal group. For DEXA values, T scores of L2-L4, L2, L3, L4, femur neck, trochanter, Wards and Z scores of femur neck, Wards area were significantly lower in peri and postmenopausal groups. It was demonstrated paralel to literature that BMD decreased in peri and early postmenopausal women associated with hormone profile changes, mainly lower E2.

  8. Would male hormonal contraceptives affect cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Michael Zitzmann

    2018-01-01

    Full Text Available The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years, a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

  9. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

    Directory of Open Access Journals (Sweden)

    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  10. BIOTECHNOLOGY OF RECOMBINANT HORMONES IN DOPING

    Directory of Open Access Journals (Sweden)

    Biljana Vitošević

    2011-09-01

    Full Text Available Recombinant DNA technology has allowed rapid progress in creating biosynthetic gene products for the treatment of many diseases. In this way it can produce large amounts of hormone, which is intended for the treatment of many pathological conditions. Recombinant hormones that are commonly used are insulin, growth hormone and erythropoietin. Precisely because of the availability of these recombinant hormones, it started their abuse by athletes. Experiments in animal models confirmed the potential effects of some of these hormones in increasing physical abilities, which attracted the attention of athletes who push the limits of their competitive capability by such manipulation. The risks of the use of recombinant hormones in doping include serious consequences for the health of athletes. Methods of detection of endogenous hormones from recombined based on the use of a monoclonal antibodies, capillary zone electrophoresis and protein biomarkers

  11. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  12. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  13. 'Femoral head necrosis' in metabolic and hormonal osteopathies

    International Nuclear Information System (INIS)

    Heuck, F.H.W.; Treugut, H.

    1984-01-01

    The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. (orig.) [de

  14. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  15. Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women.

    Science.gov (United States)

    Wise, L A; Troisi, R; Hatch, E E; Titus, L J; Rothman, K J; Harlow, B L

    2015-06-01

    Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

  16. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

    Science.gov (United States)

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  17. Menopause and menopausal hormone therapy in women: cardiovascular benefits and risks

    Directory of Open Access Journals (Sweden)

    Anna Svatikova

    2018-01-01

    Full Text Available The last decade has brought many challenges and uncertainties regarding the use of menopausal hormone therapy in women. Two early key studies, the Heart and Estrogen/Progestin Replacement Study (HERS and the Women's Health Initiative (WHI failed to prove beneficial effects of exogenous estrogen, and estrogen combined with progestin, in cardiovascular prevention. More recent studies, however, introduced the concept of a possible “window-of-opportunity” for hormonal therapy, in which menopausal hormone therapy is used early after the onset of menopause, and may lead to more favorable, cardio-protective outcomes. Despite the increasing wealth of clinical data, menopausal hormone therapy is not currently recommended for primary or secondary prevention of coronary heart disease in women. Further research is needed to understand the risk-benefit balance of menopausal hormone therapy. Resumen: La última década ha traído muchos retos e incertidumbres respecto al uso de la terapia hormonal en la menopausia en mujeres. Dos estudios tempranos clave, el Heart and Estrogen/Progestin Replacement Study (HERS [Estudio del Corazón y Reemplazo de Estrógeno/Progestina] y la Womeńs Health Initiative (WHI [Iniciativa de Salud de la Mujer] no pudieron demostrar los efectos benéficos del estrógeno exógeno y el estrógeno combinado con la progestina, en la prevención cardiovascular. Sin embargo, estudios más recientes han introducido el concepto de una posible “ventana de oportunidad” para la terapia hormonal, en donde la terapia hormonal en la menopausia se emplea tempranamente luego del inicio de la menopausia, y que puede llevar a resultados más favorables y cardioprotectores. A pesar de la creciente riqueza en datos clínicos, en la actualidad no se recomienda la terapia hormonal en la menopausia para la prevención primaria o secundaria de la enfermedad coronaria en mujeres. Se requiere m

  18. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-01-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  19. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-02-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  20. Levels of central oxytocin and glucocorticoid receptor and serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability.

    Science.gov (United States)

    Qiao, Xufeng; Yan, Yating; Tai, Fadao; Wu, Ruiyong; Hao, Ping; Fang, Qianqian; Zhang, Shuwei

    2014-11-01

    Sociability is the prerequisite to social living. Oxytocin and the hypothalamo-pituitary-adrenocortical axis mediate various social behaviors across different social contexts in different rodents. We hypothesized that they also mediate levels of non-reproductive social behavior. Here we explored naturally occurring variation in sociability through a social preference test and compared central oxytocin, glucocorticoid receptors, serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability. We found that low-social voles showed higher levels of anxiety-like behavior in open field tests, and had more serum adrenocorticotropic hormone and corticosterone than high-social voles. High-social individuals had more glucocorticoid receptor positive neurons in the hippocampus and more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than low-social individuals. Within the same level of sociability, females had more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than males. These results indicate that naturally occurring social preferences are associated with higher levels of central oxytocin and hippocampus glucocorticoid receptor and lower levels of anxiety and serum adrenocorticotropic hormone and corticosterone. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. PALBOCICLIB IN COMBINATION WITH HORMONE THERAPY FOR LUMINAL HER2-NEGATIVE METASTATIC BREAST CANCER: NEW HIGHLY EFFECTIVE STRATEGY OF DRUG TREATMENT

    Directory of Open Access Journals (Sweden)

    E. V. Artamonova

    2017-01-01

    Full Text Available The review considers a new oral targeted drug palbociclib and its place in treatment of luminal (estrogen receptor-positive HER2– metastatic breast cancer. The results of randomized clinical trials have shown that inclusion of palbociclib in various hormone therapy regimens for treatment of HER2– metastatic breast cancer with expression of estrogen receptors allows to significantly improve clinical outcomes and increase survival, objective response rate and its duration, as well as clinical benefit rate (CBR. Addition of palbociclib to letrozole in the 1st line hormone therapy or to fulvestrant in patients with progression at/after previous endocrine therapy increased progression-free survival in all groups irrespective of clinical characteristics, tumor progression, or expression of molecular markers mediating development of hormone resistance. The main adverse events associated with palbociclib were neutropenia, leukopenia and thrombocytopenia, but overall hematological toxicity was manageable, and the therapy itself was safe. This strategy received a “breakthrough therapy designation” from the experts and combines proven effectiveness and satisfactory tolerability, allows to maintain high quality of life, and should be prescribed to patients with luminal HER2– metastatic breast cancer.

  2. Physical growth, puberty and hormones in adolescents with Nodding Syndrome; a pilot study.

    Science.gov (United States)

    Piloya-Were, Theresa; Odongkara-Mpora, Beatrice; Namusoke, Hanifa; Idro, Richard

    2014-11-28

    Nodding syndrome is an epidemic symptomatic generalized epilepsy syndrome of unknown cause in Eastern Africa. Some patients have extreme short stature. We hypothesized that growth failure in nodding syndrome is associated with specific endocrine dysfunctions. In this pilot study, we examined the relationship between serum hormone levels and stature, bone age and sexual development. We recruited ten consecutive children, 13 years or older, with World Health Organization defined nodding syndrome and assessed physical growth, bone age, development of secondary sexual characteristics and serum hormone levels. Two children with incomplete results were excluded. Of the eight remaining, two had severe stunting (height for age Z [HAZ] scorebone age was delayed by a median 3(range 0-4) years. Serum growth hormone levels were normal in all eight but the two patients with severe stunting and one with moderate stunting had low levels of Somatomedin C (Insulin like Growth Factor [IGF1]) and/or IGF binding protein 3 (IGFBP3), mediators of growth hormone function. A linear relationship was observed between serum IGF1 level and HAZ score. With the exception of one child, all were either pre-pubertal or in early puberty (Tanner stages 1 and 2) and in the seven, levels of the gonadotrophins (luteinising and follicle stimulating hormone) and the sex hormones (testosterone/oestrogen) were all within pre-pubertal ranges or ranges of early puberty. Thyroid function, prolactin, adrenal, and parathyroid hormone levels were all normal. Patients with nodding syndrome may have dysfunctions in the pituitary growth hormone and pituitary gonadal axes that manifest as stunted growth, delayed bone age and puberty. Studies are required to determine if such endocrine dysfunction is a primary manifestation of the disease or a secondary consequence of chronic ill health and malnutrition and if so, whether targeted interventions can improve outcome.

  3. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  4. The thyroid hormone, parathyroid hormone and vitamin D associated hypertension

    Directory of Open Access Journals (Sweden)

    Sandeep Chopra

    2011-01-01

    Full Text Available Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two.

  5. Thyroid hormone metabolism in poultry

    Directory of Open Access Journals (Sweden)

    Darras V.M.

    2000-01-01

    Full Text Available Thyroid hormone (TH receptors preferentially bind 3.5,3'-triiodothyronine (T3. Therefore the metabolism of thyroxine (T4 secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T3, plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type 1 deiodinase (D1 catalyses both outer ring (ORD and inner ring deiodinalion (IRD. Type II deiodinase (D2 only catalyses ORD while type III (D3 only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels off, inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T3 availability and hence in

  6. Association of Hormonal Contraception With Depression

    DEFF Research Database (Denmark)

    Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

    2016-01-01

    to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Conclusions and Relevance: Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first......Importance: Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. Objective: To investigate...... whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. Design, Setting, and Participants: This nationwide prospective cohort study combined data from the National Prescription Register...

  7. Free thyroid hormones in health and disease

    International Nuclear Information System (INIS)

    Bueber, V.

    1984-01-01

    Several groups of patients with normal and abnormal thyroid function as well as patients with goitre on hormone substitution are discussed with respect to the diagnostic value of the free thyroid hormone methods. The free T 3 technique under investigation separates clearly between euthyroidism and hyperthyroidism, however, during application of contraceptive pills and during pregnancy free T 3 is slightly enhanced. Free T 4 can be found in the normal range even in hypothyroidism, during T 4 substitution free T 4 is useful for control of adequate hormone substitution. Free thyroid hormones are advantageous to be performed with respect to practicability compared to the estimation of total hormone concentrations by enzyme as well as radioimmunoassay. Normally there is no additional demand for measurement of thyroid hormone binding proteins, another rather economical argument for using these parameters in thyroid diagnosis. (orig.) [de

  8. Anticoncepción hormonal

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    1997-02-01

    Full Text Available Se realizó una revisión de los anticonceptivos hormonales con énfasis en aspectos que van desde su descubrimiento, el mecanismo de acción, los diferentes tipos y formas de utilización, así como el esquema de administración terapéutica en algunas entidades, sus indicaciones, ventajas y contraindicaciones: A review of the hormonal contraceptives was carried out, emphasizing on features from their discovery, trigger mechanism, different kinds, and ways to use them, as well as the scheme of the therapeutical administration in some entities, its indications, advantages, and contraindications.

  9. Inhibitors of plant hormone transport

    Czech Academy of Sciences Publication Activity Database

    Klíma, Petr; Laňková, Martina; Zažímalová, Eva

    2016-01-01

    Roč. 253, č. 6 (2016), s. 1391-1404 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD15088 Institutional support: RVO:61389030 Keywords : polar auxin transport * acid-binding protein * gnom arf-gef * equilibrative nucleoside transporter * efflux carrier polarity * plasma-membrane-protein * cultured tobacco cells * arabidopsis-thaliana * gravitropic response * brefeldin-a * Plant hormones * Transport * Inhibitors * Auxin * Cytokinins * Strigolactones * Abscisic acid * Cell biology Subject RIV: ED - Physiology Impact factor: 2.870, year: 2016

  10. Thyroid hormones and cardiac arrhythmias

    Czech Academy of Sciences Publication Activity Database

    Tribulová, N.; Knezl, V.; Shainberg, A.; Seki, S.; Soukup, Tomáš

    2010-01-01

    Roč. 52, 3-4 (2010), s. 102-112 ISSN 1537-1891 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant - others:VEGA(SK) 2/0049/09; APVV(SK) 51-059505; APVV(SK) 51-017905 Institutional research plan: CEZ:AV0Z50110509 Keywords : thyroid hormone * arrhythmias * ion channels * connexin-43 Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 2.174, year: 2010

  11. Growth hormone insensitivity syndrome: A sensitive approach

    Directory of Open Access Journals (Sweden)

    Soumik Goswami

    2012-01-01

    Full Text Available Patients with Growth Hormone Insensitivity have characteristic phenotypic features and severe short stature. The underlying basis are mutations in the growth hormone receptor gene which gives rise to a characteristic hormonal profile. Although a scoring system has been devised for the diagnosis of this disorder, it has not been indisputably validated. The massive expense incurred in the diagnosis and treatment of this condition with suboptimal therapeutic response necessitates a judicious approach in this regard in our country.

  12. Pituitary-hormone secretion by thyrotropinomas

    OpenAIRE

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

    2008-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore ev...

  13. Simultaneous radioimmunoassay for luteinizing hormone and prolactin

    International Nuclear Information System (INIS)

    Steele, M.K.; Deschepper, C.F.

    1985-01-01

    A combined radioimmunoassay (RIA) for the measurement of the anterior pituitary proteins luteinizing hormone (LH) and prolactin (PRL) is described and compared with individual RIAs for these hormones. The standard curves and the sample values for LH and PRL were identical when determined in a combined or in an individual RIA. This technique may prove useful to a number of laboratories where it is desirable to determine levels of more than one hormone in limited sample volumes

  14. Growth Hormone and Craniofacial Tissues. An update

    OpenAIRE

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the ...

  15. Minireview: Hormones and human sexual orientation.

    Science.gov (United States)

    Balthazart, Jacques

    2011-08-01

    Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion. First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development. Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality. It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined.

  16. Radiotherapy, chemotherapy, and growth-hormone deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Schiliro, G; Russo, A; Sciotto, A; Distefano, G; Vigo, R [Catania Univ. (Italy). 1. and 2. Paediatric Clinics

    1976-11-06

    Measurements have been made of the growth hormone (GH) responses of nine children with acute lymphoblastic leukaemia to the insulin and arginine tolerance tests. All the patients had received induction treatment with prednisone, vincristine and doxorubicin ('Adriamycin') for 4 weeks followed by 2400 rad of orthovoltage cranial irradiation plus five intrathecal injections of methotrexate. During the study all the children were in complete remission, which had been maintained with 6-mercaptopurine and methotrexate for 4 to 26 months. No pulses of steroids were used in remission. Five patients in early remission did not respond to either stimulation test, three having longer remissions showed a late and low response to the insulin test and the one patient with the longest remission (26 months) had a normal GH response. Heights and bone ages were normal. These results, which suggest the possibility of a gradual recovery after the end of CNS treatment including orthovoltage cranial irradiation, are contrasted with those for megavoltage treatment reported by Shalet et al. (Shalet, S.M., Beardwell, C.G., Morris-Jones, P.H., Pearson, D., Archs. Dis. Childh., 1976, vol. 51, 489).

  17. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol....... A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...... levels in men. The peak levels of both LH and testosterone were observed during June-July, with minimum levels present during winter-early spring. Air temperature, rather than light exposure, seems to be a possible climatic variable explaining the seasonal variation in LH levels....

  18. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

    2013-01-01

    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  19. Effects of hormones on platelet aggregation.

    Science.gov (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

    2014-04-01

    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  20. Hormones and the blood-brain barrier.

    Science.gov (United States)

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

    2015-03-01

    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  1. Gastrointestinal Hormones Induced the Birth of Endocrinology.

    Science.gov (United States)

    Wabitsch, Martin

    2017-01-01

    The physiological studies by British physiologists William Maddock Bayliss and Ernest Henry Starling, at the beginning of the last century, demonstrated the existence of specific messenger molecules (hormones) circulating in the blood that regulate the organ function and physiological mechanisms. These findings led to the concept of endocrinology. The first 2 hormones were secretin, discovered in 1902, and gastrin, discovered in 1905. Both hormones that have been described are produced in the gut. This chapter summarizes the history around the discovery of these 2 hormones, which is perceived as the birth of endocrinology. It is noteworthy that after the discovery of these 2 gastrointestinal hormones, many other hormones were detected outside the gut, and thereafter gut hormones faded from both the clinical and scientific spotlight. Only recently, the clinical importance of the gut as the body's largest endocrine organ producing a large variety of hormones has been realized. Gastrointestinal hormones are essential regulators of metabolism, growth, development and behavior and are therefore the focus of a modern pediatric endocrinologist. © 2017 S. Karger AG, Basel.

  2. Determinants of Growth Hormone Resistance in Malnutrition

    Science.gov (United States)

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    States of under-nutrition are characterized by growth hormone resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies result in elevated growth hormone levels and low levels of IGF-I. We review various states of malnutrition and a disease state characterized by chronic under-nutrition -- anorexia nervosa -- and discuss possible mechanisms contributing to the state of growth hormone resistance, including FGF-21 and SIRT1. We conclude by examining the hypothesis that growth hormone resistance is an adaptive response to states of under-nutrition, in order to maintain euglycemia and preserve energy. PMID:24363451

  3. Hormones as doping in sports.

    Science.gov (United States)

    Duntas, Leonidas H; Popovic, Vera

    2013-04-01

    Though we may still sing today, as did Pindar in his eighth Olympian Victory Ode, "… of no contest greater than Olympia, Mother of Games, gold-wreathed Olympia…", we must sadly admit that today, besides blatant over-commercialization, there is no more ominous threat to the Olympic games than doping. Drug-use methods are steadily becoming more sophisticated and ever harder to detect, increasingly demanding the use of complex analytical procedures of biotechnology and molecular medicine. Special emphasis is thus given to anabolic androgenic steroids, recombinant growth hormone and erythropoietin as well as to gene doping, the newly developed mode of hormones abuse which, for its detection, necessitates high-tech methodology but also multidisciplinary individual measures incorporating educational and psychological methods. In this Olympic year, the present review offers an update on the current technologically advanced endocrine methods of doping while outlining the latest procedures applied-including both the successes and pitfalls of proteomics and metabolomics-to detect doping while contributing to combating this scourge.

  4. Selective thyroid hormone receptor modulators

    Directory of Open Access Journals (Sweden)

    Girish Raparti

    2013-01-01

    Full Text Available Thyroid hormone (TH is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various thyroid hormone receptors (TR isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in therapeutics. These findings were followed by search of compounds with isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1 isoform of TR. More recently, eprotirome was developed and has been studied in humans. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity. Another compound, 3,5-diiodothyropropionic acid (DITPA, binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in heart failure (HF. In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in thyrotoxicosis and cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.

  5. Hormonal mechanisms of cooperative behaviour

    Science.gov (United States)

    Soares, Marta C.; Bshary, Redouan; Fusani, Leonida; Goymann, Wolfgang; Hau, Michaela; Hirschenhauser, Katharina; Oliveira, Rui F.

    2010-01-01

    Research on the diversity, evolution and stability of cooperative behaviour has generated a considerable body of work. As concepts simplify the real world, theoretical solutions are typically also simple. Real behaviour, in contrast, is often much more diverse. Such diversity, which is increasingly acknowledged to help in stabilizing cooperative outcomes, warrants detailed research about the proximate mechanisms underlying decision-making. Our aim here is to focus on the potential role of neuroendocrine mechanisms on the regulation of the expression of cooperative behaviour in vertebrates. We first provide a brief introduction into the neuroendocrine basis of social behaviour. We then evaluate how hormones may influence known cognitive modules that are involved in decision-making processes that may lead to cooperative behaviour. Based on this evaluation, we will discuss specific examples of how hormones may contribute to the variability of cooperative behaviour at three different levels: (i) within an individual; (ii) between individuals and (iii) between species. We hope that these ideas spur increased research on the behavioural endocrinology of cooperation. PMID:20679116

  6. Hormesis and Female Sex Hormones

    Directory of Open Access Journals (Sweden)

    Elvar Theodorsson

    2011-05-01

    Full Text Available Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.

  7. Long acting injectable hormonal contraceptives.

    Science.gov (United States)

    Fraser, I S

    1982-03-01

    Injectable hormonal preparations can be highly effective and satisfactory contraceptives. The two main preparations available today are depot medroxy progesterone acetate (DMPA) and norethisterone oenanthate (NET-OEN), but several other approaches are currently under clinical trial. Injectable contraceptives have some unique advantages which give them justifiably wide appeal amongst many groups of women. However, they do have a number of disadvantages including invariable menstrual disturbance and a delay in the return of fertility. One formulation of DMPA, Depo-Provera, is probably the most extensively investigated single hormonal contraceptive ever made. These studies indicate that it is remarkably safe and does not face any more unresolved issues than the combined pill, intrauterine device or tubal sterilization. However, for a number of disparate emotional and political reasons it has attracted the attention of several consumer and feminist groups, who have waged a prolonged and quite unjustified campaign against it. It is to be hoped that future debate will be conducted on a more informed, rational and less emotional basis. Injectable contraceptives should have an important place in the family planning armamentarium of all countries, and current developments should lead to a decrease in concerns about presently available agents. This should further increase the widespread acceptability of this approach to contraception.

  8. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  9. The Determinations of Estrogen and Progesterone Receptor in Breast Cancer Cell by Radioimmunoassay Method

    International Nuclear Information System (INIS)

    Kim, Chi Yeul

    1981-01-01

    The estrogen and progesterone receptors which are bound to the cytoplasmic protein of cancer cells were measured in 20 patients with the early breast cancer by means of radioimmunoassay using charcoal. 1) The patients with estrogen receptor positive were 13 (65%) of 20 cases and with progestrone receptor positive were 7 cases (35%) in the early breast cancer. 2) Coexistence of estrogen and progesterone receptor positive was noted in 7 cases (35%). The cases of estrogen receptor positive and progesterone receptor negative were 6 cases (33.3%), while there were no cases of estrogen receptor negative with progesterone receptor positive. 3) Coincidence of estrogen and progesterone negative was noticed in 7 cases (35%). Conclusively it is considered that the measurement of estrogen and progesterone receptors has relevance as predictive value, in the response to hormonal manipulations and chemotherapy for breast cancer patients.

  10. Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience.

    Science.gov (United States)

    Ciccarese, Mariangela; Fabi, Alessandra; Moscetti, Luca; Cazzaniga, Maria Elena; Petrucelli, Luciana; Forcignanò, Rosachiara; Lupo, Laura Isabella; De Matteis, Elisabetta; Chiuri, Vincenzo Emanuele; Cairo, Giuseppe; Febbraro, Antonio; Giordano, Guido; Giampaglia, Marianna; Bilancia, Domenico; La Verde, Nicla; Maiello, Evaristo; Morritti, Maria; Giotta, Francesco; Lorusso, Vito; Latorre, Agnese; Scavelli, Claudio; Romito, Sante; Cusmai, Antonio; Palmiotti, Gennaro; Surico, Giammarco

    2017-06-01

    This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7-11) (A), 10 months (95% CI 9-11) (B), and 5 months (95% CI 2-8) (C), p = 0.956. OS was 38 months (95% CI 24-38) (A), median not reached (B), and 13 months (95% CI 10-25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3-4), asthenia 46.0% (6.1% grade 3-4), hypercholesterolemia 46.0% (0.6% grade 3-4), and hyperglycemia 35.6% (5.5% grade 3-4). The main reason for discontinuation/interruption was grade 2-3 stomatitis. No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.

  11. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1990-01-01

    It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic...

  12. Wheat seed enhancement by vitamin and hormonal priming

    International Nuclear Information System (INIS)

    Khan, M.B.; Gurchani, M.A.; Hussain, M.

    2011-01-01

    Seed priming has proven beneficial in many important agricultural crops. The present study was conducted to explore the role (if any) of hormonal and vitamin seed priming to improve the germination, seedling emergence, early seedling establishment, electrolyte leakage and nutrients uptake in wheat seedlings. The wheat seeds were soaked for 48 hours in aerated solution of salicylic acid, ascorbic acid, kinetin and GA3 with 20 ppm concentration of each solution, whereas untreated seeds were taken as control. Seed priming with ascorbic acid resulted in maximum final germination and emergence percentage (FGP and FEP), radical and plumule length, root and shoot length, number of secondary roots, root shoot ratio, root dry weight, shoot dry weight and seedling dry weight compared to control (untreated seeds). Minimum mean germination and emergence time (MGT and MET) was recorded in seeds primed with kinetin and GA3. While in case of biochemical attributes, seedling potassium contents were decreased by hormonal seed priming while total soluble sugars were increased by salicylic acid and ascorbic acid seed priming. Hormonal seed priming had non-significant effect on phosphorus seedling contents. Untreated (Control) seeds showed maximum electrical conductivity at 0.5, 1, 2, 6, 12 and 24 h after inbibition than primed seeds against the minimum electrical conductivity that was recorded in seeds primed with salicylic acid and ascorbic acid. In conclusion, the wheat seeds primed with 20 ppm solution of ascorbic acid may be used for wheat seed invigoration. (author)

  13. The effects of whole-body irradiation on the serum levels and kinetics of thyroid hormones in rats

    International Nuclear Information System (INIS)

    Gray, W.M.

    1980-01-01

    The effects of a single whole-body dose of X-rays on the serum levels and kinetics of thyroid hormones in rats were studied. The influence of radiation-induced anorexia was monitored by using pair fed control groups. A dose of 800 rad caused a reduction in T 4 levels and 750 rad had a similar effect on T 3 ; in each case the control group showed a smaller reduction. The kinetic results indicated that, in the control groups, the early reduction in hormone concentrations was caused by decreased production, whereas, in the irradiated groups, it was caused by a change in the distribution of the hormone; however the continuing reduction in hormone levels in the irradiated rats appeared to result from decreased production. The results suggest that the thyroid system may play an active part in the early metabolic changes which follow whole-body irradiation. (author)

  14. Thyroid hormones, interpersonal violence and personality traits : clinical studies in high-risk psychiatric cohorts

    OpenAIRE

    Sinai, Cave

    2015-01-01

    Suicidal and violent behaviors as well as early life adversity are prevalent in clinical high-risk populations. Early life adversity is related to developmental dysregulation of behavioral and emotional traits. The neuroendocrine systems involved in the development of dysfunctional behavior and impulsive aggressive traits are not fully known. The overall aim of this thesis was to investigate the relationship between thyroid hormones and personality traits, as well as to exposur...

  15. Glucoregulatory function of thyroid hormones: role of pancreatic hormones

    International Nuclear Information System (INIS)

    Mueller, M.J.B.; Burger, A.G.; Ferrannini, E.; Jequier, E.; Acheson, K.J.

    1989-01-01

    Glucose metabolism was investigated in humans before and 14 days after 300 micrograms L-thyroxine (T4)/day using a sequential clamp protocol during short-term somatostatin infusion (500 micrograms/h, 0-6 h) at euglycemia (0-2.5 h), at 165 mg/dl (2.5-6 h), and during insulin infusion (1.0 mU.kg-1.min-1, 4.5-6 h). T4 treatment increased plasma T4 (+96%) and 3,5,3'-triiodothyronine (T3, +50%), energy expenditure (+8%), glucose turnover (+32%), and glucose oxidation (Glucox +87%) but decreased thyroid-stimulating hormone (-96%) and nonoxidative glucose metabolism (Glucnonox, -30%) at unchanged lipid oxidation (Lipox). During somatostatin and euglycemia glucose production (Ra, -67%) and disposal (Rd, -28%) both decreased in euthyroid subjects but remained at -22% and -5%, respectively, after T4 treatment. Glucox (control, -20%; +T4, -25%) fell and Lipox increased (control, +42%; +T4, +45%) in both groups, whereas Glucnonox decreased before (-36%) but increased after T4 (+57%). During somatostatin infusion and hyperglycemia Rd (control, +144%; +T4, +84%) and Glucnonox (control, +326%; +T4, +233%) increased, whereas Glucox and Lipox remained unchanged. Insulin further increased Rd (+76%), Glucox (+155%), and Glucnonox (+50%) but decreased Ra (-43%) and Lipox (-43%). All these effects were enhanced by T4 (Rd, +38%; Glucox, +45%; Glucnonox, +35%; Ra, +40%; Lipox, +11%). Our data provide evidence that, in humans, T3 stimulates Ra and Rd, which is in part independent of pancreatic hormones

  16. DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.

    Science.gov (United States)

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  17. Hormones of choice: the neuroendocrinology of partner preference in animals.

    Science.gov (United States)

    Henley, C L; Nunez, A A; Clemens, L G

    2011-04-01

    Partner preference behavior can be viewed as the outcome of a set of hierarchical choices made by an individual in anticipation of mating. The first choice involves approaching a conspecific verses an individual of another species. As a rule, a conspecific is picked as a mating partner, but early life experiences can alter that outcome. Within a species, an animal then has the choice between a member of the same sex or the opposite sex. The final choice is for a specific individual. This review will focus on the middle choice, the decision to mate with either a male or a female. Available data from rats, mice, and ferrets point to the importance of perinatal exposure to steroid hormones in the development of partner preferences, as well as the importance of activational effects in adulthood. However, the particular effects of this hormone exposure show species differences in both the specific steroid hormone responsible for the organization of behavior and the developmental period when it has its effect. Where these hormones have an effect in the brain is mostly unknown, but regions involved in olfaction and sexual behavior, as well as sexually dimorphic regions, seem to play a role. One limitation of the literature base is that many mate or 'partner preference studies' rely on preference for a specific stimulus (usually olfaction) but do not include an analysis of the relation, if any, that stimulus has to the choice of a particular sexual partner. A second limitation has been the almost total lack of attention to the type of behavior that is shown by the choosing animal once a 'partner' has been chosen, specifically, if the individual plays a mating role typical of its own sex or the opposite sex. Additional paradigms that address these questions are needed for better understanding of partner preferences in rodents. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

    Science.gov (United States)

    Ramachandran Pillai, R; Sharon, Leena; Premkumar, Nancy R; Kattimani, Shivanand; Sagili, Haritha; Rajendiran, Soundravally

    2017-01-01

    Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The barrier within: endothelial transport of hormones.

    Science.gov (United States)

    Kolka, Cathryn M; Bergman, Richard N

    2012-08-01

    Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and fun