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https://www.readbyqxmd.com/read/29352052/estrogen-receptor-positive-breast-cancer-exploiting-signaling-pathways-implicated-in-endocrine-resistance
#1
REVIEW
Adam M Brufsky, Maura N Dickler
Advancements in molecular profiling and endocrine therapy (ET) have led to more focused clinical attention on precision medicine. These advances have expanded our understanding of breast cancer (BC) pathogenesis and hold promising implications for the future of therapy. The estrogen receptor-α is a predominant endocrine regulatory protein in the breast and in estrogen-induced BC. Successful targeting of proteins and genes within estrogen receptor (ER) nuclear and nonnuclear pathways remains a clinical goal...
January 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29351904/er%C3%AE-mediated-nuclear-sequestration-of-rsk2-is-required-for-er-breast-cancer-tumorigenesis
#2
Katarzyna A Ludwik, Oliver Gene McDonald, David R Brenin, Deborah A Lannigan
Although ribosomal protein S6 kinase A3 (RSK) activation status positively correlates with patient responses to anti-estrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of ER+ breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N-terminus to activate a pro-neoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29349773/progestin-only-and-combined-oral-contraceptives-and-receptor-defined-premenopausal-breast-cancer-risk-the-norwegian-women-and-cancer-study
#3
Marit Busund, Nora S Bugge, Tonje Braaten, Marit Waaseth, Charlotta Rylander, Eiliv Lund
Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of this study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort - The Norwegian Women and Cancer study (NOWAC)...
January 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29349762/advances-in-endocrine-therapy-for-postmenopausal-metastatic-breast-cancer
#4
Lisa E Flaum, William J Gradishar
A majority of breast cancers are hormone receptor (HR) positive and are responsive to various types of hormone manipulation. Endocrine therapy is the preferred first-line therapy for patients with advanced estrogen receptor (ER) positive, HER2-negative breast cancer who do not have symptomatic visceral disease. Endocrine therapy is often continued in the second- and third-line setting, with chemotherapy deferred until tumor becomes endocrine therapy refractory and/or a visceral crisis in imminent. Therapeutic options vary based on clinical presentation and include single-agent therapies such as tamoxifen, aromatase inhibitors and fulvestrant, and combination therapies options...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349448/a-study-on-platinum-iv-species-containing-an-estrogen-receptor-modulator-to-reverse-tamoxifen-resistance-of-breast-cancer
#5
Weiwei Hu, Jian Zhao, Wuyang Hua, Shaohua Gou
Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and platinum(ii) drugs were designed and synthesized for targeting estrogen receptors (ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity against breast cancer cells, but also reversed the tamoxifen resistance of TamR-MCF-7 cancer cells. Computational docking assays together with cellular uptake data demonstrated that the ER ligand portion of these conjugates plays a targeting role in ER-positive tumor cells and promotes the uptake of platinum via an estrogen receptor-mediated pathway...
January 19, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29348822/the-localization-of-pre-mrna-splicing-factor-prpf38b-is-a-novel-prognostic-biomarker-that-may-predict-survival-benefit-of-trastuzumab-in-patients-with-breast-cancer-overexpressing-her2
#6
Tarek M A Abdel-Fatah, Robert C Rees, A Graham Pockley, Paul Moseley, Graham R Ball, Stephen Y T Chan, Ian O Ellis, Amanda K Miles
Cancer biomarkers that can define disease status and provide a prognostic insight are essential for the effective management of patients with breast cancer (BC). The prevalence, clinicopathological and prognostic significance of PRPF38B expression in a consecutive series of 1650 patients with primary invasive breast carcinoma were examined using immunohistochemistry. Furthermore, the relationship(s) between clinical outcome and PRPF38B expression was explored in 627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with HER2-overexpressing disease...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348368/defining-the-physiological-role-of-srp-in-protein-targeting-efficiency-and-specificity
#7
Elizabeth A Costa, Kelly Subramanian, Jodi Nunnari, Jonathan S Weissman
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes N-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the N terminus...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348189/cancer-stem-cell-phenotypes-in-er-breast-cancer-models-are-promoted-by-pelp1-aib1-complexes
#8
Thu H Truong, Hsiangyu Hu, Nuri A Temiz, Kyla Hagen, Brian J Girard, Nicholas J Brady, Kathryn L Schwertfeger, Carol A Lange, Julie H Ostrander
Proline, glutamic acid, and leucine rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, interacting partners unique to cytoplasmic PELP1 and the mechanisms by which these interactions promote oncogenic PELP1 signaling were sought...
January 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#9
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345338/miat-lncrna-is-overexpressed-in-breast-cancer-and-its-inhibition-triggers-senescence-and-g1-arrest-in-mcf7-cell-line
#10
Firooz Jannat Alipoor, Malek Hossein Asadi, Masoud Torkzadeh-Mahani
Long non-coding RNAs are known as key regulators in the progression and metastasis of breast cancer. Miat originally has been considered as an lncRNA to be associated with a susceptibility to myocardial infarction. Here, we have detected the expression of Miat in different cancer cells and a series of breast tumor tissue. Miat expression was much higher in high-grade tumors compared to low-grade ones. Unlike P53 positive tumors, Miat expression was upregulated in ER, PR, Her2 positive tumor tissues. Knockdown Miat suppressed breast cancer cell proliferation and caused G1 arrest in cell cycle...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345254/the-mtor-inhibitor-azd8055-overcomes-tamoxifen-resistance-in-breast-cancer-cells-by-down-regulating-hspb8
#11
Jia-Jie Shi, Si-Meng Chen, Chen-Liang Guo, Yi-Xue Li, Jian Ding, Ling-Hua Meng
Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#12
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342924/estrogen-and-thyroid-hormone-receptor-activation-by-medicinal-plants-from-bahia-brazil
#13
Luã Tainã Costa Reis, Magnus Régios Dias da Silva, Silvia Lima Costa, Eudes da Silva Velozo, Ronan Batista, Suzana Telles da Cunha Lima
Background: A number of medicinal plants are traditionally used for metabolic disorders in Bahia state, Brazil. The aim of this study was to evaluate the estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts prepared from 20 plants. Methods: Species were extracted and assayed for receptor activation through both ER and TR gene-reporter assays, using 17β-estradiol and triiodothyronine (T3), respectively, as the positive controls. Results: Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria verticillata (Rubiaceae) were able to activate ER as much as the positive control (17β-estradiol)...
January 15, 2018: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29340524/efficacy-of-removal-of-cariogenic-bacteria-and-carious-dentin-by-ablation-using-different-modes-of-er-yag-lasers
#14
A Baraba, L Kqiku, D Gabrić, Ž Verzak, K Hanscho, I Miletić
The primary objective of this in vitro study was to evaluate the efficiency of removal of cariogenic bacteria and carious dentin by ablation using two lasers: fluorescence-feedback controlled (FFC) Er:YAG laser and different pulses of Er:YAG laser based on variable square pulse technology (VSPt). The secondary objective was to measure the temperature during laser ablation of carious tissue. Seventy-two extracted human molars were used in this study. Sixty teeth with carious dentin were randomly divided into four experimental groups according to the treatment for caries removal: group 1: 400 µs (FFC group); group 2: super short pulse (SSP group, 50 µs pulse); group 3: medium short pulse (MSP group, 100 µs pulse); group 4: short pulse (SP group, 300 µs pulse) and one positive control group with no treatment...
January 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29339359/genetic-variants-in-immune-related-pathways-and-breast-cancer-risk-in-african-american-women-in-the-amber-consortium
#15
Chi-Chen Hong, Lara E Sucheston-Campbell, Song Liu, Qiang Hu, Song Yao, Kathryn L Lunetta, Stephen A Haddad, Edward A Ruiz-Narváez, Jeannette T Bensen, Ting-Yuan David Cheng, Elisa V Bandera, Lynn A Rosenberg, Christopher A Haiman, Kelvin P Lee, Sharon S Evans, Scott I Abrams, Elizabeth A Repasky, Andrew F Olshan, Julie R Palmer, Christine B Ambrosone
BACKGROUND: Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women. METHODS: A total of 13,235 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based pathway analyses were conducted using the adaptive rank truncated product statistic for overall breast cancer risk, and risk by estrogen receptor (ER) status...
January 16, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29338553/comprehensive-clinicopathologic-and-updated-immunohistochemical-characterization-of-primary-ovarian-mucinous-carcinoma
#16
Dina Bassiouny, Nadia Ismiil, Valerie Dubé, Guangming Han, Matthew Cesari, Fang-I Lu, Elzbieta Slodkowska, Carlos Parra-Herran, Hak Fai Chiu, Magda Naeim, Nim Li, Mahmoud Khalifa, Sharon Nofech-Mozes
The distinction of primary mucinous ovarian carcinoma (PMOC) from other primaries or secondaries is essential for selecting therapeutic options and prognostication. We aimed to characterize the immunohistochemical profile of 36 PMOCs using an extended immunohistochemical panel, with clinicopathologic features and outcome. PAX8 was negative in 30 (83.3%), and SATB2 was negative in 32/35. HNF1B, AMACR, and napsin-A were detected in 33 (91.7%), 35 (97.2%), and 0 (0%), respectively. MMR proteins and ARID1A were retained in 100%; PTEN was lost in 4 (11...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29337187/metabolomics-reveals-that-dietary-xenoestrogens-alter-cellular-metabolism-induced-by-palbociclib-letrozole-combination-cancer-therapy
#17
Benedikt Warth, Philipp Raffeiner, Ana Granados, Tao Huan, Mingliang Fang, Erica M Forsberg, H Paul Benton, Laura Goetz, Caroline H Johnson, Gary Siuzdak
Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications...
January 10, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29335875/seasonal-variation-and-source-apportionment-of-pm2-5-bound-trace-elements-at-a-coastal-area-in-southwestern-taiwan
#18
Su-Lun Hwang, Miao-Ching Chi, Su-Er Guo, Yu-Ching Lin, Chiang-Ting Chou, Chieh-Mo Lin
The aim of this study is to investigate the seasonal variations and source apportionment on atmospheric fine particulate matter (PM2.5) mass and associated trace element concentrations at a coastal area, in Chiayi County of southwestern Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements in PM2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Multiple approaches of the enrichment factor (EF) analysis and positive matrix fraction (PMF) model were used to identify potential sources of PM2...
January 16, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29334839/bax-inhibitor-1-is-required-for-resisting-the-early-brain-injury-induced-by-subarachnoid-hemorrhage-through-regulating-ire1-jnk-pathway
#19
Lei Shi, Zaizong Wang, Xianjin Liu, Mao Li, Shangfei Zhang, Xiaobin Song
Background and Purpose Bax inhibitor-1 (BI-1) has been identified as a suppressor of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress-induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to explore the neuroprotective functions of BI-1 in EBI after SAH by using models of SAH that induced endovascular perforation in rats. Method The neurological score, brain water content and blood-brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators...
January 16, 2018: Neurological Research
https://www.readbyqxmd.com/read/29334159/a-gold-iii-pincer-ligand-scaffold-for-the-synthesis-of-binuclear-and-bioconjugated-complexes-synthesis-and-anticancer-potential
#20
Bertrand Benoît, Maria A O'Connell, Zöe A E Waller, Manfred Bochmann
Cyclometalated (C^N^C)Au(III) complexes bearing functionalized N-heterocyclic carbene (NHC) ligands provide a high-yielding, modular route to bioconjugated and binuclear complexes. That methodology has been applied to the synthesis of bioconjugated complexes presenting biotin and 17α-ethynylestradiol vectors, as well as to the synthesis of bimetallic Au(III)/Au(I) complexes. The in vitro antiproliferative activities of these compounds against various cancer cells lines depend on the linker length, with the longer linker being the most potent...
January 15, 2018: Chemistry: a European Journal
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