Hormones & Cancer最新文献_第2页

Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1. 调控ESR1转录调控的内在和外在因素。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-08-01 Epub Date: 2020-06-26 DOI: 10.1007/s12672-020-00388-0

David K Lung, Rebecca M Reese, Elaine T Alarid

{"title":"Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1.","authors":"David K Lung, Rebecca M Reese, Elaine T Alarid","doi":"10.1007/s12672-020-00388-0","DOIUrl":"https://doi.org/10.1007/s12672-020-00388-0","url":null,"abstract":"Transcriptional regulation of ESR1, the gene that encodes for estrogen receptor α (ER), is critical for regulating the downstream effects of the estrogen signaling pathway in breast cancer such as cell growth. ESR1 is a large and complex gene that is regulated by multiple regulatory elements, which has complicated our understanding of how ESR1 expression is controlled in the context of breast cancer. Early studies characterized the genomic structure of ESR1 with subsequent studies focused on identifying intrinsic (chromatin environment, transcription factors, signaling pathways) and extrinsic (tumor microenvironment, secreted factors) mechanisms that impact ESR1 gene expression. Currently, the introduction of genomic sequencing platforms and additional genome-wide technologies has provided additional insight on how chromatin structures may coordinate with these intrinsic and extrinsic mechanisms to regulate ESR1 expression. Understanding these interactions will allow us to have a clearer understanding of how ESR1 expression is regulated and eventually provide clues on how to influence its regulation with potential treatments. In this review, we highlight key studies concerning the genomic structure of ESR1, mechanisms that affect the dynamics of ESR1 expression, and considerations towards affecting ESR1 expression and hormone responsiveness in breast cancer.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"129-147"},"PeriodicalIF":3.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00388-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38095969","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}

引用次数: 21

Advanced Adrenocortical Carcinoma (ACC): a Review with Focus on Second-Line Therapies. 晚期肾上腺皮质癌 (ACC)：以二线疗法为重点的综述。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-08-01 Epub Date: 2020-04-17 DOI: 10.1007/s12672-020-00385-3

Luke Ardolino, Aaron Hansen, Stephen Ackland, Anthony Joshua

{"title":"Advanced Adrenocortical Carcinoma (ACC): a Review with Focus on Second-Line Therapies.","authors":"Luke Ardolino, Aaron Hansen, Stephen Ackland, Anthony Joshua","doi":"10.1007/s12672-020-00385-3","DOIUrl":"10.1007/s12672-020-00385-3","url":null,"abstract":"Advanced adrenocortical cancer (ACC) is a rare, highly aggressive malignancy, which typically has a poor prognosis. In advanced ACC, the overall trend is toward a short PFS interval following first-line systemic therapy, highlighting a clear need for improved second-/third-line treatment strategies. We conducted a review of the literature and relevant scientific guidelines related to systemic therapy for advanced ACC. Public indexes including PubMed/MEDLINE were searched. Treatment selection in the second-line setting is based on small phase 2 trials, case reports, and pre-clinical evidence. The best data available for initial second-line therapy selection supports the use of gemcitabine and capecitabine (G + C) or streptozotocin (S), both with or without mitotane. G + C is becoming increasingly recommended based on phase 2 clinical trial data in patients of good PS, due to the inferred superior PFS and OS from non-comparative trials. Alternatively, streptozotocin was better tolerated than EDP + M in the FIRM-ACT study and remains an option when warranted. Beyond this, further treatment approaches should be tailored to individual patient characteristics, utilizing a mixture of systemic therapies, local therapies, and enrolment in clinical trials where available. Additionally, the role of molecular stratification, predictive biomarkers, and immune checkpoint inhibitors in specific individuals, such as Lynch syndrome, is evolving and may become increasingly utilized in clinical practice. Advanced ACC necessitates a multidisciplinary approach and is best managed in a specialist center. Although there is no one definitive second-line treatment strategy, there are some favorable approaches, which require further validation in larger clinical trials.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"11 3-4","pages":"155-169"},"PeriodicalIF":3.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355245/pdf/12672_2020_Article_385.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205589","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}

引用次数: 0

Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer. 家族性非髓样甲状腺癌家族中缺乏POT1基因突变。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 DOI: 10.1007/s12672-020-00383-5

Aida Orois, Celia Badenas, Jordi L Reverter, Verónica López, Miriam Potrony, Mireia Mora, Irene Halperin, Josep Oriola

{"title":"Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer.","authors":"Aida Orois, Celia Badenas, Jordi L Reverter, Verónica López, Miriam Potrony, Mireia Mora, Irene Halperin, Josep Oriola","doi":"10.1007/s12672-020-00383-5","DOIUrl":"https://doi.org/10.1007/s12672-020-00383-5","url":null,"abstract":"To date, the genes involved in familial non-medullary thyroid cancer (FNMTC) remain poorly understood, with the exception of syndromic cases of FNMTC. It has been proposed that germline mutations in telomere-related genes, such as POT1, described in familial melanoma might also predispose individuals to thyroid cancer, requiring further research. We aimed to identify germline mutations in POT1 in selected FNMTC families (with at least three affected members) without a history of other cancers or other features, and to describe the clinical characteristics of these families. Sequencing of the 5'UTR and coding regions of POT1 was performed in seven affected people (index cases) from seven families with FNMTC. In addition, we performed whole-exome sequencing (WES) of DNA from 10 affected individuals belonging to four of these families. We did not find germline variants of interest in POT1 by Sanger sequencing or WES. We neither found putative causative mutations in genes previously described as candidate genes for FNMTC in the 4 families studied by WES. In our study, no germline potentially pathogenic mutations were detected in POT1, minimizing the possibilities that this gene could be substantially involved in non-syndromic FNMTC.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"11 2","pages":"111-116"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00383-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223778","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}

引用次数: 9

Progesterone Receptor Gene Variants in Metastatic Estrogen Receptor Positive Breast Cancer. 转移性雌激素受体阳性乳腺癌的孕激素受体基因变异

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 Epub Date: 2020-01-16 DOI: 10.1007/s12672-020-00377-3

Amy M Fowler, Kelley Salem, Michael DeGrave, Irene M Ong, Shane Rassman, Ginny L Powers, Manoj Kumar, Ciara J Michel, Aparna M Mahajan

{"title":"Progesterone Receptor Gene Variants in Metastatic Estrogen Receptor Positive Breast Cancer.","authors":"Amy M Fowler, Kelley Salem, Michael DeGrave, Irene M Ong, Shane Rassman, Ginny L Powers, Manoj Kumar, Ciara J Michel, Aparna M Mahajan","doi":"10.1007/s12672-020-00377-3","DOIUrl":"https://doi.org/10.1007/s12672-020-00377-3","url":null,"abstract":"Tumor mutations in the gene encoding estrogen receptor alpha (ESR1) have been identified in metastatic breast cancer patients with endocrine therapy resistance. However, relatively little is known about the occurrence of mutations in the progesterone receptor (PGR) gene in this population. The study objective was to determine the frequency and prognostic significance of tumor PGR mutations for patients with estrogen receptor (ER)-positive metastatic breast cancer. Thirty-five women with metastatic or locally recurrent ER+ breast cancer were included in this IRB-approved, retrospective study. Targeted next-generation sequencing of the PGR gene was performed on isolated tumor DNA. Associations between mutation status and clinicopathologic factors were analyzed as well as overall survival (OS) from time of metastatic diagnosis. The effect of the PGR variant Y890C (c.2669A>G) identified in this cohort on PR transactivation function was tested using ER-PR- (MDA-MB-231), ER+PR+ (T47D), and ER+PR- (T47D PR KO) breast cancer cell lines. There were 71 occurrences of protein-coding PGR variants in 67% (24/36; 95% CI 49-81%) of lesions. Of the 49 unique variants, 14 are single nucleotide polymorphisms (SNPs). Excluding SNPs, the median OS of patients with PGR variants was 32 months compared to 79 months with wild-type PGR (p = 0.42). The most frequently occurring (4/36 lesions) non-SNP variant was Y890C. Cells expressing Y890C had reduced progestin-stimulated PR transactivation compared to cells expressing wild-type PR. PGR variants occur frequently in ER+ metastatic breast cancer. Although some variants are SNPs, others are predicted to be functionally deleterious as demonstrated with Y890C PR.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"63-75"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00377-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547595","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}

引用次数: 15

Cytoplasmic ERα and NFκB Promote Cell Survival in Mouse Mammary Cancer Cell Lines. 细胞质ERα和NFκB促进小鼠乳腺癌细胞系细胞存活。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 Epub Date: 2020-02-01 DOI: 10.1007/s12672-020-00378-2

Emily Smart, Luis H Alejo, Jonna Frasor

{"title":"Cytoplasmic ERα and NFκB Promote Cell Survival in Mouse Mammary Cancer Cell Lines.","authors":"Emily Smart, Luis H Alejo, Jonna Frasor","doi":"10.1007/s12672-020-00378-2","DOIUrl":"https://doi.org/10.1007/s12672-020-00378-2","url":null,"abstract":"There is a desperate need in the field for mouse mammary tumors and cell lines that faithfully mimic estrogen receptor (ER) expression and activity found in human breast cancers. We found that several mouse mammary cancer cell lines express ER but fail to demonstrate classical estrogen-driven proliferation or transcriptional activity. We investigated whether these cell lines may be used to model tamoxifen resistance by using small molecule inhibitors to signaling pathways known to contribute to resistance. We found that the combination of NFκB inhibition and ER antagonists significantly reduced cell proliferation in vitro, as well as growth of syngeneic tumors. Surprisingly, we found that ER was localized to the cytoplasm, regardless of any type of treatment. Based on this, we probed extra-nuclear functions of ER and found that co-inhibition of ER and NFκB led to an increase in oxidative stress and apoptosis. Together, these findings suggest that cytoplasmic ER and NFκB may play redundant roles in protecting mammary cancer cells from oxidative stress and cell death. Although this study has not identified a mouse model with classical ER activity, cytoplasmic ER has been described in a small subset of human breast tumors, suggesting that these findings may be relevant for some breast cancer patients.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"76-86"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00378-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37599730","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}

引用次数: 8

Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells. 雌二醇通过pelp1介导的膜启动信号在er α阳性乳腺癌细胞中诱导MMP-9表达。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 DOI: 10.1007/s12672-020-00380-8

Yu Pan, Xiuli Wang, Yanzhi Zhang, Juanjuan Qiao, Hironobu Sasano, Keely McNamara, Baoshan Zhao, Dongmei Zhang, Yuhua Fan, Lili Liu, Xueling Jia, Ming Liu, Sihang Song, Lin Wang

{"title":"Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells.","authors":"Yu Pan, Xiuli Wang, Yanzhi Zhang, Juanjuan Qiao, Hironobu Sasano, Keely McNamara, Baoshan Zhao, Dongmei Zhang, Yuhua Fan, Lili Liu, Xueling Jia, Ming Liu, Sihang Song, Lin Wang","doi":"10.1007/s12672-020-00380-8","DOIUrl":"https://doi.org/10.1007/s12672-020-00380-8","url":null,"abstract":"Proline-, glutamic acid-, leucine-rich protein 1 (PELP1) is a novel estrogen receptor (ER) coregulator, demonstrated distinctive characters from other ERα coregulators, and has been suggested to be involved in metastasis of several cancers. In ERα-positive breast cancer, PELP1 overexpression enhanced ruffles and filopodium-like structure stimulated by estradiol (E2) through extranuclear cell signaling transduction hereby increased cell motility. However, whether PELP1 is also involved in extracellular matrix remodeling of ERα-positive breast cancer cells is still unknown. In this study, we investigated the role of PELP1 in E2-induced MMP-9 expression and the underlined mechanism. The results demonstrated the following: E2-induced ERα-positive MCF-7 breast cancer cell MMP-9 mRNA and protein expression in a rapid response and concentration-dependent manner. Knocked down PELP1 significantly suppressed E2-induced MMP-9 expression. E2-bovine serum albumin (BSA), a large molecular membrane-impenetrable conjugate of E2, can also upregulate MMP-9 protein expression in MCF-7, and the action of E2-BSA can be abolished by PI3K inhibitor LY294002; treating MCF-7 simultaneously with PELP1-shRNA and LY294002 did not show synergetic inhibitory effect on E2-BSA-induced MMP-9 expression. Our results indicated that estrogen-induced MMP-9 expression in ER-positive breast cancer cells may be through PELP1-mediated PI3K/Akt signaling pathway.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"11 2","pages":"87-96"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00380-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847444","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}

引用次数: 10

Baicalein Is a Phytohormone that Signals Through the Progesterone and Glucocorticoid Receptors. 黄芩素是一种通过黄体酮和糖皮质激素受体发出信号的植物激素。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 Epub Date: 2020-03-07 DOI: 10.1007/s12672-020-00382-6

Julia R Austin, Brenna J Kirkpatrick, Rocío Rivera Rodríguez, Michael E Johnson, Daniel D Lantvit, Joanna E Burdette

{"title":"Baicalein Is a Phytohormone that Signals Through the Progesterone and Glucocorticoid Receptors.","authors":"Julia R Austin, Brenna J Kirkpatrick, Rocío Rivera Rodríguez, Michael E Johnson, Daniel D Lantvit, Joanna E Burdette","doi":"10.1007/s12672-020-00382-6","DOIUrl":"https://doi.org/10.1007/s12672-020-00382-6","url":null,"abstract":"While flavonoids have been studied extensively for estrogen receptor activity, they have not been well studied for their ability to modify progesterone receptor (PR) and glucocorticoid receptor (GR) signaling. Three flavonoid compounds, tangeretin, wogonin, and baicalein, were selected for testing for PR and GR activity based on their structural similarity to known phytoprogesterone-like compounds. Each compound was docked in the binding pocket of PR and GR. Of these compounds, baicalein was predicted to be most likely to bind to both receptors. A fluorescence polarization competitive binding assay for PR and GR confirmed that baicalein binds to both the PR and GR with IC50 values of 15.30 μM and 19.26 μM, respectively. In Ishikawa PR-B and T47D cells, baicalein acted as a PR antagonist in a hormone response element (HRE) luciferase (Luc) assay. In OVCAR5 cells, which only express GR, baicalein was a GR agonist via an HRE/Luc assay and induced GR target genes, FKBP5 and GILZ. RU486, a PR and GR antagonist, abrogated baicalein's activity in OVCAR5 cells, confirming baicalein's activity is mediated through the GR. In vivo, baicalein administered intraperitoneally to female mice twice a week for 4 weeks at a dose of 25 mg/kg induced the GR target gene GILZ in the reproductive tract, which was blocked by RU486. In summary, baicalein has PR antagonist and GR agonist activity in vitro and demonstrates GR agonist activity in the uterus in vivo.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"97-110"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00382-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37716765","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}

引用次数: 10

The Role of mPRδ and mPRε in Human Glioblastoma Cells: Expression, Hormonal Regulation, and Possible Clinical Outcome. mPRδ和mPRε在人胶质母细胞瘤细胞中的作用:表达、激素调节和可能的临床结果。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-04-01 DOI: 10.1007/s12672-020-00381-7

Aylin Del Moral-Morales, Juan Carlos González-Orozco, José Moisés Capetillo-Velázquez, Ana Gabriela Piña-Medina, Ignacio Camacho-Arroyo

{"title":"The Role of mPRδ and mPRε in Human Glioblastoma Cells: Expression, Hormonal Regulation, and Possible Clinical Outcome.","authors":"Aylin Del Moral-Morales, Juan Carlos González-Orozco, José Moisés Capetillo-Velázquez, Ana Gabriela Piña-Medina, Ignacio Camacho-Arroyo","doi":"10.1007/s12672-020-00381-7","DOIUrl":"https://doi.org/10.1007/s12672-020-00381-7","url":null,"abstract":"Glioblastomas (GBM) are the most frequent and aggressive primary tumor of the central nervous system. In recent years, it has been proposed that sex hormones such as progesterone play an essential role in GBM biology. Membrane progesterone receptors (mPRs) are a group of G protein-coupled receptors with a wide distribution and multiple functions in the organism. There are five mPRs subtypes described in humans: mPRα, mPRβ, mPRγ, mPRδ, and mPRε. It has been reported that human-derived GBM cells express the mPRα, mPRβ, and mPRγ subtypes, and that progesterone promotes GBM progression in part by mPRα specific activation; however, it is still unknown if mPRδ and mPRε are also expressed in this type of tumor cells. In this study, we characterized the expression and hormonal regulation of mPRδ and mPRε in human GBM cells. We also analyzed a set of biopsies from TCGA. We found that the expression of these receptors is dependent on the tumor's grade and that mPRδ expression is directly correlated to patients' survival while the opposite is observed for mPRε. By RT-qPCR, Western blot, and immunofluorescence, the expression of mPRδ and mPRε was detected for the first time in human GBM cells. An in silico analysis showed possible progesterone response elements in the promoter regions of mPRδ and mPRε, and progesterone treatments downregulated the expression of these receptors. Our results suggest that mPRδ and mPRε are expressed in human GBM cells and that they are relevant to GBM biology.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"11 2","pages":"117-127"},"PeriodicalIF":3.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-020-00381-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847443","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}

引用次数: 14

Progesterone and Breast Cancer: an NCI Workshop Report. 黄体酮和乳腺癌:NCI研讨会报告。

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-02-01 DOI: 10.1007/s12672-020-00379-1

Neeraja Sathyamoorthy, Carol A Lange

引用次数: 12

Elevated Free Thyroxine Levels Are Associated with Poorer Overall Survival in Patients with Gastroesophageal Cancer: A Retrospective Single Center Analysis. 胃食管癌患者游离甲状腺素水平升高与较差的总生存率相关:一项回顾性单中心分析

IF 3 4区医学

Hormones & Cancer Pub Date : 2020-02-01 DOI: 10.1007/s12672-019-00374-1

H C Puhr, P Wolf, A S Berghoff, S F Schoppmann, M Preusser, Aysegul Ilhan-Mutlu

{"title":"Elevated Free Thyroxine Levels Are Associated with Poorer Overall Survival in Patients with Gastroesophageal Cancer: A Retrospective Single Center Analysis.","authors":"H C Puhr, P Wolf, A S Berghoff, S F Schoppmann, M Preusser, Aysegul Ilhan-Mutlu","doi":"10.1007/s12672-019-00374-1","DOIUrl":"https://doi.org/10.1007/s12672-019-00374-1","url":null,"abstract":"As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (p = 0.041, HR = 2.202) and lower levels of T3 (p = 0,003, HR = 0,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283 days; hyperthyroid, 354 days; hypothyroid, 284 days; p = 0.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"11 1","pages":"42-51"},"PeriodicalIF":3.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-019-00374-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847439","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}

引用次数: 10