Hormones & Cancer最新文献

{"title":"O-GlcNAc-Dependent Regulation of Progesterone Receptor Function in Breast Cancer.","authors":"Gloria M Trinca,&nbsp;Merit L Goodman,&nbsp;Evangelia K Papachristou,&nbsp;Clive S D'Santos,&nbsp;Prabhakar Chalise,&nbsp;Rashna Madan,&nbsp;Chad Slawson,&nbsp;Christy R Hagan","doi":"10.1007/s12672-017-0310-9","DOIUrl":"https://doi.org/10.1007/s12672-017-0310-9","url":null,"abstract":"<p><p>Emerging clinical trial data implicate progestins in the development of breast cancer. While the role for the progesterone receptor (PR) in this process remains controversial, it is clear that PR, a steroid-activated nuclear receptor, alters the transcriptional landscape of breast cancer. PR interacts with many different types of proteins, including transcriptional co-activators and co-repressors, transcription factors, nuclear receptors, and proteins that post-translationally modify PR (i.e., kinases and phosphatases). Herein, we identify a novel interaction between PR and O-GlcNAc transferase (OGT), the enzyme that catalyzes the addition of a single N-acetylglucosamine sugar, referred to as O-GlcNAc, to acceptor serines and threonines in target proteins. This interaction between PR and OGT leads to the post-translational modification of PR by O-GlcNAc. Moreover, we show that O-GlcNAcylated PR is more transcriptionally active on PR-target genes, despite the observation that PR messenger RNA and protein levels are decreased when O-GlcNAc levels are high. O-GlcNAcylation in breast cancer is clinically relevant, as we show that O-GlcNAc levels are higher in breast cancer as compared to matched normal tissues, and PR-positive breast cancers have higher levels of OGT. These data predict that under conditions where O-GlcNAc levels are high (breast cancer), PR, through an interaction with the modifying enzyme OGT, will exhibit increased O-GlcNAcylation and potentiated transcriptional activity. Therapeutic strategies aimed at altering cellular O-GlcNAc levels may have profound effects on PR transcriptional activity in breast cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 1","pages":"12-21"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0310-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin, Leptin, and Insulin-Pathway Receptors as Endometrial Cancer Subtyping Markers.","authors":"Evan L Busch,&nbsp;Marta Crous-Bou,&nbsp;Jennifer Prescott,&nbsp;Michael J Downing,&nbsp;Bernard A Rosner,&nbsp;George L Mutter,&nbsp;Immaculata De Vivo","doi":"10.1007/s12672-017-0318-1","DOIUrl":"https://doi.org/10.1007/s12672-017-0318-1","url":null,"abstract":"<p><p>Developing a system of molecular subtyping for endometrial tumors might improve insight into disease etiology and clinical prediction of patient outcomes. High body mass index (BMI) has been implicated in development of endometrial cancer through hormonal pathways and might influence tumor expression of biomarkers involved in BMI-sensitive pathways. We evaluated whether endometrial tumor expression of 7 markers from BMI-sensitive pathways of insulin resistance could effectively characterize molecular subtypes: adiponectin receptor 1, adiponectin receptor 2, leptin receptor, insulin receptor (beta subunit), insulin receptor substrate 1, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 receptor. Using endometrial carcinoma tissue specimens from a case-only prospective sample of 360 women from the Nurses' Health Study, we scored categorical immunohistochemical measurements of protein expression for each marker. Logistic regression was used to estimate associations between endometrial cancer risk factors, especially BMI, and tumor marker expression. Proportional hazard modeling was performed to estimate associations between marker expression and time to all-cause mortality as well as time to endometrial cancer-specific mortality. No association was observed between BMI and tumor expression of any marker. No marker was associated with time to either all-cause mortality or endometrial cancer-specific mortality in models with or without standard clinical predictors of patient mortality (tumor stage, grade, and histologic type). It did not appear that any of the markers evaluated here could be used effectively to define molecular subtypes of endometrial cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"33-39"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0318-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35704902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma.","authors":"F I Moulana,&nbsp;A A H Priyani,&nbsp;M V C de Silva,&nbsp;R S Dassanayake","doi":"10.1007/s12672-017-0315-4","DOIUrl":"https://doi.org/10.1007/s12672-017-0315-4","url":null,"abstract":"<p><p>Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 1","pages":"1-11"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0315-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin Use and Breast Cancer Prognosis in Black and White Women.","authors":"Amanda Leiter,&nbsp;Nina A Bickell,&nbsp;Derek LeRoith,&nbsp;Anupma Nayak,&nbsp;Sheldon M Feldman,&nbsp;Neil B Friedman,&nbsp;Alison Estabrook,&nbsp;Tari A King,&nbsp;Kezhen Fei,&nbsp;Rebeca Franco,&nbsp;Emily J Gallagher","doi":"10.1007/s12672-017-0312-7","DOIUrl":"https://doi.org/10.1007/s12672-017-0312-7","url":null,"abstract":"<p><p>Studies show decreased risk of breast cancer recurrence and improved survival with statin use, but data on racial disparities regarding breast cancer prognosis and statin use are lacking. Our objective was to investigate if racial disparities in breast cancer prognosis can be partially explained by differences in pre-diagnosis statin use. Patients were identified from a prospective, multicenter study examining the effects of metabolic factors on breast cancer prognosis in Black and White women. Statin use, prognosis (as measured by Nottingham Prognostic Index), anthropometric, tumor, and socio-demographic characteristics were examined. Five hundred eighty-seven women (487 White, 100 Black) with newly diagnosed primary invasive breast cancer were recruited. Obesity was more prevalent in Black women than White women (47 vs 19%, p < 0.01); both groups had similar low-density lipoprotein (LDL) cholesterol levels (113 ± 41 vs 113 ± 36 mg/dl, p = 0.90). More Black women used statins than White women (18 vs 11%, p = 0.06). Black women had a worse prognosis in an adjusted model than White women (OR 2.13 95% CI 1.23-3.67). Statin use was not associated with prognosis in unadjusted (OR 1.03, 95% CI 0.53-2.0) and adjusted models (OR 1.14, 95% CI 0.56-2.31). In women with newly diagnosed breast cancer, Black women were more likely to be treated with statins than White women, contrary to previous studies. Black women had worse prognosis than White women, but this difference was not explained by differences in pre-diagnosis statin use. Our study suggests that differences in pre-diagnosis statin use do not contribute to racial disparities in breast cancer prognosis.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 1","pages":"55-61"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0312-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors.","authors":"Delphine Vezzosi,&nbsp;Christine Do Cao,&nbsp;Ségolène Hescot,&nbsp;Jérôme Bertherat,&nbsp;Magali Haissaguerre,&nbsp;Vanina Bongard,&nbsp;Delphine Drui,&nbsp;Christelle De La Fouchardière,&nbsp;Frédéric Illouz,&nbsp;Françoise Borson-Chazot,&nbsp;Bodale Djobo,&nbsp;Amandine Berdelou,&nbsp;Antoine Tabarin,&nbsp;Martin Schlumberger,&nbsp;Claire Briet,&nbsp;Philippe Caron,&nbsp;Sophie Leboulleux,&nbsp;Rossella Libe,&nbsp;Eric Baudin","doi":"10.1007/s12672-017-0313-6","DOIUrl":"https://doi.org/10.1007/s12672-017-0313-6","url":null,"abstract":"<p><p>A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 1","pages":"62-69"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0313-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interplay Between Epithelial-Mesenchymal Transition (EMT) and the Thyroid Hormones-αvβ3 Axis in Ovarian Cancer.","authors":"Chen Weingarten,&nbsp;Yonatan Jenudi,&nbsp;Rami Yair Tshuva,&nbsp;Dotan Moskovich,&nbsp;Adi Alfandari,&nbsp;Aleck Hercbergs,&nbsp;Paul J Davis,&nbsp;Martin Ellis,&nbsp;Osnat Ashur-Fabian","doi":"10.1007/s12672-017-0316-3","DOIUrl":"https://doi.org/10.1007/s12672-017-0316-3","url":null,"abstract":"<p><p>Ovarian cancer is a highly metastatic disease. The metastatic potential is enhanced by epithelial to mesenchymal transition (EMT) in which αvβ3 integrin plays a role. Thyroid hormones (L-thyroxine, T4, and 3,5,3'-triiodo-L-thyronine, T3) bind this integrin, and we hypothesized that the thyroid hormone-αvβ3 axis may be involved in EMT activity in ovarian cancer. The transcription (mRNA), protein abundance (westerns), and protein localization (fluorescence microscopy) of several EMT markers were studied in ovarian cancer cells (OVCAR-3, A2780, and SKOV-3) treated with 1 nM T3 or 100 nM T4 for 1-24 h. The protein levels of β-catenin, and its downstream targets, zeb-1, slug, and vimentin, were significantly induced by both hormones, while the effect on transcription was limited. The pre-incubation of the cells overnight with two integrin inhibitors, RGD (0.1-10 μM) or αvβ3 blocking antibody (1-100 ng/mL), prevented the induction of β-catenin by T3 and zeb-1 by T4, indicating direct integrin involvement. The transcription of the mesenchymal markers, β-catenin, zeb-1, slug/snail, vimentin, and n-cadherin was hardly affected by T3 and T4, while that of the epithelial markers, e-cadherin and zo-1, was inhibited. Our results suggest a novel role for the thyroid hormone-αvβ3 axis in EMT, with possible implications for ovarian cancer metastasis.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 1","pages":"22-32"},"PeriodicalIF":3.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0316-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Resveratrol Treatment Reduces the Risk of Mammary Carcinogenesis in Female Offspring Prenatally Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin.","authors":"Tássia C de Lima E Silva,&nbsp;Livia T R da Silveira,&nbsp;Mariana F Fragoso,&nbsp;Flávia R M da Silva,&nbsp;Meire F Martinez,&nbsp;Joyce R Zapaterini,&nbsp;Odair H G Diniz,&nbsp;Wellerson R Scarano,&nbsp;Luis F Barbisan","doi":"10.1007/s12672-017-0304-7","DOIUrl":"https://doi.org/10.1007/s12672-017-0304-7","url":null,"abstract":"<p><p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) presents adverse effects on breast development/carcinogenesis. This study aimed to identify the ability of resveratrol (Res) to modify the adverse effects of TCDD in a female offspring. Pregnant female Wistar rats were allocated into four groups: TCDD, TCDD + Res, Res, and control. TCDD (1 μg/kg) was orally administered as a single dose on gestational day (GD) 15, and Res was orally administered during GD10-21 and lactation at a dose of 20 mg/kg/day. Female offsprings were euthanized on a specific postnatal day (PND) for hormonal analysis (PND 22, 48-51), vaginal opening (PND 30-48), and mammary gland morphology (PND 22). Other females received two doses of N-nitroso-N-methylurea (MNU, 50 mg/kg) on PNDs 22 and 51 and were euthanized on PND 24 (Ki-67, ER-α and apoptosis indexes or molecular analysis) or PND 180 (tumor assay). TCDD exposure altered the development of the mammary structure while these alterations were partially improved by maternal Res. Two days after first MNU administration, some genes associated with apoptosis were altered in the mammary tissue from the TCDD group (Bax and Caspase 3 down- and Bcl-2 upregulated) but were also partially reestablished by maternal Res. Mammary gland bcl-2 and bcl-xl proteins expression was increased while the apoptosis index was reduced by TCDD exposure but restored by maternal Res. An increase in number of mammary tumors was observed in female offspring from the TCDD group compared to the other groups. The results indicate that most mammary changes induced in female offspring through TCDD exposure or after MNU administrations were reduced by maternal resveratrol treatment.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"286-297"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0304-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients.","authors":"Julien Hadoux,&nbsp;Marie Terroir,&nbsp;Sophie Leboulleux,&nbsp;Frederic Deschamps,&nbsp;Abir Al Ghuzlan,&nbsp;Ségolène Hescot,&nbsp;Lambros Tselikas,&nbsp;Isabelle Borget,&nbsp;Caroline Caramella,&nbsp;Desirée Déandréis,&nbsp;Diane Goere,&nbsp;Thierry De Baere,&nbsp;Martin Schlumberger,&nbsp;Eric Baudin","doi":"10.1007/s12672-017-0303-8","DOIUrl":"https://doi.org/10.1007/s12672-017-0303-8","url":null,"abstract":"<p><p>Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1-4). Median PFS was 17.2 months (95% CI [12.1-58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5). Median overall survival was 7.5 years (95% CI [4-NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"330-337"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0303-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parity and Risk of Thyroid Cancer: a Population-Based Study in Lithuania.","authors":"L Zabuliene,&nbsp;D Jasilionis,&nbsp;E Miseikyte-Kaubriene,&nbsp;R Stukas,&nbsp;A Kaceniene,&nbsp;G Smailyte","doi":"10.1007/s12672-017-0308-3","DOIUrl":"https://doi.org/10.1007/s12672-017-0308-3","url":null,"abstract":"<p><p>An association between parity and thyroid cancer risk has been investigated in a number of independent studies but yielded contradictory findings. The aim of this study was to explore the association between parity and thyroid cancer risk. The population-based cohort study in Lithuanian was conducted. The study dataset based on the linkages between all records from the 2001 population census, all cancer incidence records from the Lithuanian Cancer Registry, and all death and emigration records from Statistics Lithuania for the period between 6 April 2001 and 31 December 2009. Cox's proportional hazards regression models were used to estimate the hazard ratios (HRs) for parity, age at first birth, number of children, place of residence, education, and age at census. The cohort of 868,105 women was followed for 8.6 years, and 1775 thyroid cancer cases were diagnosed during the study period. The significantly higher thyroid cancer risk was observed among parous women (HR = 1.45, 95% CI: 1.20, 1.75) and in women with 1, 2, and 3 children, after adjusting for the possible confounding effects of relevant demographic variables. The findings of this study are consistent with the hypothesis that parity might be associated with the risk of thyroid cancer in women.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"325-329"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0308-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer.","authors":"Helena Pópulo,&nbsp;Bruno Nunes,&nbsp;Cristina Sampaio,&nbsp;Rui Batista,&nbsp;Marta Teixeira Pinto,&nbsp;Tiago B Gaspar,&nbsp;Leandro Miranda-Alves,&nbsp;Ren-Zhi Cai,&nbsp;Xian Yang Zhang,&nbsp;Andrew V Schally,&nbsp;Manuel Sobrinho-Simões,&nbsp;Paula Soares","doi":"10.1007/s12672-017-0307-4","DOIUrl":"https://doi.org/10.1007/s12672-017-0307-4","url":null,"abstract":"<p><p>Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer. We studied the effect of MIA602 and MIA690 on thyroid cancer in vitro, using human thyroid cancer cell lines, and in vivo, using chicken embryo chorioallantoic membrane (CAM) assays. We found that mRNA for GHRH and GHRH receptor is expressed in thyroid cell lines and in samples of thyroid tumors. Immunohistochemistry confirmed the expression of GHRHR protein in specimens of thyroid tumor. We observed that GHRH antagonists inhibited the growth and increased apoptosis of thyroid cancer cells. In vivo, the antagonists inhibited growth and angiogenesis of engrafted thyroid tumors. Our results suggest that GHRH expression may play a role in growth of thyroid cancer and that GHRH antagonists can be a therapeutic option for thyroid cancer patients.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"314-324"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0307-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}