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https://www.readbyqxmd.com/read/28924522/estradiol-as-a-targeted-late-line-therapy-in-metastatic-breast-cancer-with-estrogen-receptor-amplification
#1
Karthik Kota, Adam Brufsky, Steffi Oesterreich, Adrian Lee
Estradiol is a major regulator of growth for the subset of breast cancers that express the estrogen receptor (ER, ESR1). Strategies to block ER action, via reduction of estradiol or direct inhibition of ER, have shown major success in the prevention and treatment of breast cancer. However, most ER-positive (ER+) metastatic breast cancers (MBC) eventually become resistant to these interventions. Interestingly, high dose estrogen can induce apoptosis in breast cancer cell lines, and high-dose estrogen has been used for over 50 years as therapy for ER+ breast cancer...
July 6, 2017: Curēus
https://www.readbyqxmd.com/read/28920934/esr1-cells-in-the-ventromedial-hypothalamus-control-female-aggression
#2
Koichi Hashikawa, Yoshiko Hashikawa, Robin Tremblay, Jiaxing Zhang, James E Feng, Alexander Sabol, Walter T Piper, Hyosang Lee, Bernardo Rudy, Dayu Lin
As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvl(Esr1+) cells are indispensable for female aggression. This population was active when females attacked naturally...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28905136/highly-sensitive-detection-of-esr1-mutations-in-cell-free-dna-from-patients-with-metastatic-breast-cancer-using-molecular-barcode-sequencing
#3
Nanae Masunaga, Naofumi Kagara, Daisuke Motooka, Shota Nakamura, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). METHODS: The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR)...
September 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28893862/molecular-profile-of-nasopharyngeal-carcinoma-analysing-tumour-suppressor-gene-promoter-hypermethylation-by-multiplex-ligation-dependent-probe-amplification
#4
Marc Ooft, Jolique van Ipenburg, Rob van Loo, Rick de Jong, Cathy Moelans, Weibel Braunius, Remco de Bree, Paul van Diest, Senada Koljenović, Rob Baatenburg de Jong, Jose Hardillo, Stefan Willems
AIMS: To assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV)-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options. METHODS: We evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification...
September 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28890035/longitudinal-interactions-of-estrogen-receptor-alpha-gene-rs9340799-with-social-environmental-factors-on-depression-in-adolescents-after-wenchuan-earthquake
#5
Yue Feng, Jia Lin, Qiwei Guo, Mi Su, Ting Cao, Mei Fan, Xin Zhang, Yanjun Si, Nazakat H Memon, Ding Zhi Fang
Inconsistent relationships were reported between rs9340799 on estrogen receptor alpha gene (ESR1) and depression in previous studies. The present study was to explore the longitudinal changes of prevalence and severity of depression in 439 Chinese Han adolescents with different genotypes of ESR1 rs9340799 at 6, 12 and 18months after the 2008 Wenchuan earthquake. Social-environmental factors were collected by questionnaires from 465 high school students. Variants of rs9340799 were genotyped by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing...
September 7, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28882624/network-pharmacology-analysis-of-the-anti-cancer-pharmacological-mechanisms-of-ganoderma-lucidum-extract-with-experimental-support-using-hepa1-6-bearing-c57-bl-6-mice
#6
Ruo-Lin Zhao, Yu-Min He
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (GL) is an oriental medical fungus, which was used to prevent and treat many diseases. Previously, the effective components of Ganoderma lucidum extract (GLE) were extracted from two kinds of GL, Ganoderma lucidum (Leyss. Ex Fr.) Karst. and Ganoderma sinense Zhao, Xu et Zhang, which have been used for adjuvant anti-cancer clinical therapy for more than 20 years. However, its concrete active components and its regulation mechanisms on tumor are unclear...
September 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28882552/prognostic-and-predictive-biomarkers-in-breast-cancer-past-present-and-future
#7
REVIEW
Andrea Nicolini, Paola Ferrari, Michael J Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients...
September 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28881720/analysis-of-esr1-and-pik3ca-mutations-in-plasma-cell-free-dna-from-er-positive-breast-cancer-patients
#8
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Keiichi Murakami, Yoko Omoto, Hirotaka Iwase
BACKGROUND: The measurement of ESR1 and PIK3CA mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive method to quickly assess and monitor endocrine therapy (ET) resistant metastatic breast cancer (MBC) patients. METHODS: The subjects of this retrospective study were a total of 185 plasma samples from 86 estrogen receptor-positive BC patients, of which 151 plasma samples were from 69 MBC patients and 34 plasma samples were from 17 primary BC (PBC) patients...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881657/tumor-biomarker-conversion-between-primary-and-metastatic-breast-cancer-mrna-assessment-and-its-concordance-with-immunohistochemistry
#9
Stefan Stefanovic, Ralph Wirtz, Thomas M Deutsch, Andreas Hartkopf, Peter Sinn, Zsuzsanna Varga, Bettina Sobottka, Lakis Sotiris, Florin-Andrei Taran, Christoph Domschke, Andre Hennigs, Sara Y Brucker, Christof Sohn, Florian Schuetz, Andreas Schneeweiss, Markus Wallwiener
Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests. This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874413/a-phase-ii-trial-of-neoadjuvant-mk2206-an-akt-inhibitor-with-anastrozole-in-clinical-stage-2-or-3-pik3ca-mutant-er%C3%A2-positive-and-her2-negative-breast-cancer
#10
Cynthia X Ma, Vera Suman, Matthew P Goetz, Donald W Northfelt, Mark E Burkard, Foluso Ademuyiwa, Michael J Naughton, Julie Margenthaler, Rebecca Aft, Richard J Gray, Amye J Tevaarwerk, Lee G Wilke, Tufia C Haddad, Timothy Moynihan, Charles Loprenzi, Tina Hieken, Erica K Barnell, Zachary L Skidmore, Yan-Yang Feng, Kilannin Krysiak, Jeremy Hoog, Zhanfang Guo, Leslie Nehring, Kari B Wisinski, Elaine R Mardis, Ian S Hagemann, Kiran Vij, Souzan Sanati, Hussam Al-Kateb, Obi L Griffith, Malachi Griffith, Austin Doyle, Charles Erlichman, Matthew J Ellis
PURPOSE: Hyper-activation of AKT is common and associated with endocrine resistance in estrogen receptor positive (ER+) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer. EXPERIMENTAL DESIGN: Potential eligible patients with clinical stage II/III ER+/HER2- breast cancer were pre-registered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing...
September 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28854070/first-in-human-phase-i-study-of-the-tamoxifen-metabolite-z-endoxifen-in-women-with-endocrine-refractory-metastatic-breast-cancer
#11
Matthew P Goetz, Vera J Suman, Joel M Reid, Don W Northfelt, Michael A Mahr, Andrew T Ralya, Mary Kuffel, Sarah A Buhrow, Stephanie L Safgren, Renee M McGovern, John Black, Travis Dockter, Tufia Haddad, Charles Erlichman, Alex A Adjei, Dan Visscher, Zachary R Chalmers, Garrett Frampton, Benjamin R Kipp, Minetta C Liu, John R Hawse, James H Doroshow, Jerry M Collins, Howard Streicher, Matthew M Ames, James N Ingle
Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed a phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity. Eligibility included endocrine-refractory, estrogen receptor-positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by a 3+3 design and expansion at 40, 80, and 100 mg per day...
August 30, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28845932/-early-diagnosis-of-risk-for-developing-calcium-oxalate-urolithiasis
#12
O I Apolikhin, A V Sivkov, O V Konstantinova, P A Slominskii, T V Tupitsyna, D N Kalinichenko
AIM: To identify risk groups for calcium oxalate urolithiasis among healthy individuals and patients with urolithiasis in the Russian population using molecular genetics. MATERIALS AND METHODS: The study comprised 72 patients with calcium oxalate urolithiasis (study group) and 189 healthy adults from the general Russian population (control group). The study group consisted of 39 (54.2%) men and 33 (45.8%) women. The mean age of urolithiasis patients was 41.5+/-12...
July 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28842253/repression-of-esr1-transcription-by-myod-potentiates-letrozole-resistance-in-er%C3%AE-positive-breast-cancer-cells
#13
Qiang Zhang, Xiao-Yan Liu, Shuang Li, Zhao Zhao, Juan Li, Ming-Ke Cui, En-Hua Wang
Transcriptional silencing of estrogen receptor α (ERα) expression is an important etiology contributing to the letrozole-resistance in ERα-positive breast cancer (BCa) cells, but the transcription factors responsible for this transcriptional repression remain largely unidentified. Here we report that the expression of the basic helix-loop-helix myogenic regulatory factor MYOD was abnormally up-regulated in letrozole-resistant BCa tissues and in experimentally-induced letrozole-resistant BCa cells. Overexpression of the exogenous MYOD impaired ERα expression and potentiated letrozole-resistance in letrozole-sensitive MCF7 cells, whereas MYOD knockdown could effectively restore ERα expression and thereby promote letrozole-sensitivity in letrozole-resistant MCF-7/LR cells...
August 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28827707/juxtacrine-activity-of-estrogen-receptor-%C3%AE-in-uterine-stromal-cells-is-necessary-for-estrogen-induced-epithelial-cell-proliferation
#14
Wipawee Winuthayanon, Sydney L Lierz, Karena C Delarosa, Skylar R Sampels, Lauren J Donoghue, Sylvia C Hewitt, Kenneth S Korach
Aberrant regulation of uterine cell growth can lead to endometrial cancer and infertility. To understand the molecular mechanisms of estrogen-induced uterine cell growth, we removed the estrogen receptor α (Esr1) from mouse uterine stromal cells, where the embryo is implanted during pregnancy. Without ESR1 in neighboring stroma cells, epithelial cells that line the inside of the uterus are unable to grow due to a lack of growth factors secreted from adjacent stromal cells. Moreover, loss of stromal ESR1 caused mice to deliver fewer pups due in part due to inability of some embryos to implant in the uterus, indicating that stromal ESR1 is crucial for uterine cell growth and pregnancy...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815558/sequence-variants-in-esr1-and-oxtr-are-associated-with-mayer-rokitansky-k%C3%A3-ster-hauser-syndrome
#15
Sara Yvonne Brucker, Liliane Frank, Simone Eisenbeis, Melanie Henes, Diethelm Wallwiener, Olaf Riess, Barbara Van Eijck, Dorit Schöller, Michael Bonin, Kristin Katharina Rall
INTRODUCTION: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite of ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as cause for MRKHS exists, and is supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature...
August 16, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28810930/sex-differences-in-microrna-mrna-networks-examination-of-novel-epigenetic-programming-mechanisms-in-the-sexually-dimorphic-neonatal-hypothalamus
#16
Christopher P Morgan, Tracy L Bale
BACKGROUND: Sexual differentiation of the male brain, and specifically the stress circuitry in the hypothalamus, is primarily driven by estrogen exposure during the perinatal period. Surprisingly, this single hormone promotes diverse programs of sex-specific development that vary widely between different cell types and across the developing male brain. The complexity of this phenomenon suggests that additional layers of gene regulation, including microRNAs (miRNAs), must act downstream of estrogen to mediate this specificity...
August 15, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28810691/improvement-of-implantation-potential-in-mouse-blastocysts-derived-from-ivf-by-combined-treatment-with-prolactin-epidermal-growth-factor-and-4-hydroxyestradiol
#17
Miki Takeuchi, Misato Seki, Etsuko Furukawa, Akihito Takahashi, Kyosuke Saito, Mitsuru Kobayashi, Kenji Ezoe, Emiko Fukui, Midori Yoshizawa, Hiromichi Matsumoto
STUDY QUESTION: Can supplementation of medium with prolactin (PRL), epidermal growth factor (EGF) and 4-hydroxyestradiol (4-OH-E2) prior to embryo transfer improve implantation potential in mouse blastocysts derived from IVF? SUMMARY ANSWER: Combined treatment with PRL, EGF and 4-OH-E2 improves mouse blastocyst implantation rates, while alone, each factor is ineffective. WHAT IS KNOWN ALREADY: Blastocyst dormancy during delayed implantation caused by ovariectomy is maintained by continued progesterone treatment in mice, and estrogen injection rapidly activates blastocysts to implantation-induced status in vivo...
August 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28806841/genetic-polymorphisms-as-predictive-markers-of-response-to-growth-hormone-therapy-in-children-with-growth-hormone-deficiency
#18
Anna Maria Jung, Martin Zenker, Christina Lißewski, Denny Schanze, Stefan Wagenpfeil, Tilman Robert Rohrer
Objective Growth hormone (GH) deficiency (GHD) is commonly treated with recombinant human GH (rhGH). Individual response to rhGH therapy varies widely and there is evidence that variations in growth-related genes, e. g. the GH receptor (GHR) gene, may impact treatment response. We aimed to identify genetic polymorphisms which could serve as predictive markers of response to rhGH therapy. Methods We conducted a genetic analysis of single nucleotide polymorphisms (SNPs) and the GHR exon 3 deletion in 101 paediatric GHD patients receiving rhGH...
September 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28801227/estrogen-directly-stimulates-lhb-expression-at-the-pituitary-level-during-puberty-in-female-zebrafish
#19
Gaofei Li, Haipei Tang, Yu Chen, Yike Yin, Satoshi Ogawa, Meifeng Liu, Yin Guo, Xin Qi, Yun Liu, Ishwar S Parhar, Xiaochun Liu, Haoran Lin
The LHb expression is up-regulated during puberty in female zebrafish. However, the molecular mechanism underlying how LHb expression is regulated during puberty remains largely unknown. In this study, we found that the mRNA expression levels of lhb, fshb and cyp19a1b were up-regulated along with the puberty onset in zebrafish. Among the three nuclear estrogen receptors (nERs), the esr2b is the only type whose expression is significantly up-regulated during puberty onset in the pituitary. However, in situ hybridization results revealed that lhb mRNA was colocalized with esr1 and esr2a but not esr2b...
August 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28799536/estrogen-receptor-esr1-mutation-in-bone-metastases-from-breast-cancer
#20
Stephan Bartels, Matthias Christgen, Angelina Luft, Sascha Persing, Kai Jödecke, Ulrich Lehmann, Hans Kreipe
Activating mutations of estrogen receptor α gene (ESR1) in breast cancer can cause endocrine resistance of metastatic tumor cells. The skeleton belongs to the metastatic sides frequently affected by breast cancer. The prevalence of ESR1 mutation in bone metastasis and the corresponding phenotype are not known. In this study bone metastases from breast cancer (n=231) were analyzed for ESR1 mutation. In 27 patients (12%) (median age 73 years, range: 55-82 years) activating mutations of ESR1 were detected. The most frequent mutation was p...
August 11, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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