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Lee Yien Thang, Hong Heng See, Joselito P Quirino
The low conductivity of separation electrolytes employed in nonaqueous capillary electrophoresis (NACE) limits the use of on-line sample concentration or stacking by field enhancement. Herein, micelle-to-solvent stacking (MSS) was performed by the simple injection of a micellar solution plug prior to electrokinetic injection of sample prepared under field-enhanced stacking conditions (known as field-enhanced sample injection, FESI). The proposed approach allowed a 214-625-fold improvement in peak signals for targeted anticancer drugs (e...
December 1, 2016: Talanta
Chihua Wu, Jing Luo
BACKGROUND Long non-coding RNA (lncRNA) UCA1 is an oncogene in breast cancer. The purpose of this study was to investigate the role of UCA1 in tamoxifen resistance of estrogen receptor positive breast cancer cells. MATERIAL AND METHODS Tamoxifen sensitive MCF-7 cells were transfected for UCA1 overexpression, while tamoxifen resistant LCC2 and LCC9 cells were transfected with UCA siRNA for UCA1 knockdown. qRT-PCR was performed to analyze UCA1 expression. CCK-8 assay, immunofluorescence staining of cleaved caspase-9, and flow cytometric analysis of Annexin V/PI staining were used to assess tamoxifen sensitivity...
October 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Gary K Scott, David Chu, Ravneet Kaur, Julia Malato, Daniel E Rothschild, Katya Frazier, Serenella Eppenberger-Castori, Byron Hann, Ben Ho Park, Christopher C Benz
ERα phosphorylation at hinge site S294 (pS294) was recently shown to be essential for ER-dependent gene transcription and mediated by an unknown cyclin-dependent kinase (CDK). This study was undertaken to identify the exact CDK pathway mediating pS294 formation, and to determine if this phosphorylation event occurs with, and can be targeted to treat, the ligand-independent growth of breast cancers expressing endocrine-refractory ESR1 mutations. Using a newly developed anti-pS294 monoclonal antibody, a combination of CDK specific siRNA knockdown studies and a broad panel of CDK selective inhibitors against ligand (E2)-stimulated MCF7 cells, we first identified CDK2 as the primary mediator of pS294 formation and showed that CDK2-selective inhibitors like Dinaciclib, but not CDK4/6 inhibitors like Palbociclib, can selectively prevent pS294 formation and repress ER-dependent gene expression...
October 18, 2016: Oncotarget
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
Fadia S Youssef, Mohamed L Ashour, Mansour Sobeh, Hesham A El-Beshbishy, Abdel Nasser Singab, Michael Wink
BACKGROUND: The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant. PURPOSE: This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ruijie Liu, Hadi Khalil, Suh-Chin J Lin, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice...
2016: PloS One
Shengli Mi, Zhichang Du, Yuanyuan Xu, Zhengjie Wu, Xiang Qian, Min Zhang, Wei Sun
Tumour metastasis is an important reason for cancer death, and cancer cell migration is an important step in the process of tumour metastasis. Studying cancer cell migration is of great significance. Here, we present a novel microfluidic co-culture system and establish mild, moderate and severe cancer models by using HMEpiC and MDA-MB-231 cells to study cancer cell migration and anti-cancer drug screening. Using this device, we achieved high cell viability (over 90%) and a stable analysis of the migration ability of cancer cells...
October 20, 2016: Scientific Reports
Sieglinde Bayer, Matthias Wirth
The protein sequences of class I HDACs in mice and humans are 96-99 % identical. These highly conserved proteins have crucial roles in biological processes, such as proliferation and development, which is reflected in the lethality that occurs in conventional whole body knockout mice. Therefore, conditional knockouts are inevitable to investigate the functions of class I HDACs in mice. Here, we describe the generation of conditional class I Hdac knockout mice, using Hdac1 as an example. We explain a relatively quick procedure to generate the necessary target vectors by recombination-mediated genetic engineering and gateway techniques...
2017: Methods in Molecular Biology
Laurel L Ballantyne, Yuan Yan Sin, Osama Y Al-Dirbashi, Xinzhi Li, David J Hurlbut, Colin D Funk
Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype...
December 2016: Molecular Genetics and Metabolism Reports
Aya Matsuoka, Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Hiroko Yukawa, Shiho Sakaguchi, Natsuko Tanaka, Asaka Kodera, Mari Kamimura, Yoshihiko Naritaka, Tadao Shimizu
A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Jacqui Wise
No abstract text is available yet for this article.
October 6, 2016: BMJ: British Medical Journal
A Kenneth MacLeod, Lesley A McLaughlin, Colin J Henderson, C Roland Wolf
Tamoxifen is an oestrogen-receptor (ER) antagonist used in the treatment of breast cancer. It is a pro-drug, converted by several P450 enzymes to a primary metabolite, N-desmethyltamoxifen (NDT), which is then further modified by CYP2D6 to a pharmacologically potent secondary metabolite, 4-hydroxy-N-desmethyltamoxifen (endoxifen). Anti-depressants (ADs), which are often co-prescribed to patients receiving tamoxifen, are also metabolised by CYP2D6 and evidence suggests that a drug-drug interaction (DDI) between these agents adversely affects the outcome of tamoxifen therapy by inhibiting endoxifen formation...
October 18, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Ernesto Schiffrin
For many years we have studied models of hypertension in which endothelin-1 (ET-1) is overexpressed. These include DOCA-salt hypertensive rats, Dahl-salt sensitive rats, and stroke prone SHR, in all of which ET-1-mediated mechanisms play a role in blood pressure elevation and vascular injury. In humans we demonstrated overexpression of ET-1 in the endothelium of small arteries from stage 2 hypertensive patients. We have also produced a mouse that overexpresses human ET-1 in the endothelium using a Tie-2 promoter, which exhibited increased oxidative stress and inflammation, hypertrophic remodeling and endothelial dysfunction of small arteries but only slight blood pressure elevation...
September 2016: Journal of Hypertension
Pierre Paradis, Suellen C Coelho, Sofiane Ouerd, Júlio C Fraulob-Aquino, Stefan Offermanns, Ernesto L Schiffrin
OBJECTIVE: The mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Recently, we developed a transgenic mouse with tamoxifen-inducible endothelium-restricted human ET-1 overexpression (ieET-1) using Cre/loxP technology. ieET-1 mice exhibited a BP increase after three weeks of induction in an ET type A receptor-dependent manner, in absence of evident vascular injury. It is unknown whether long-term exposure to ET-1 overexpression results in persistent BP elevation and vascular injury...
September 2016: Journal of Hypertension
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
A Harrod, J Fulton, V T M Nguyen, M Periyasamy, L Ramos-Garcia, C-F Lai, G Metodieva, A de Giorgio, R L Williams, D B Santos, P J Gomez, M-L Lin, M V Metodiev, J Stebbing, L Castellano, L Magnani, R C Coombes, L Buluwela, S Ali
Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations...
October 17, 2016: Oncogene
Yuedong Hu, Liu Ningning, Yanyan Chen
We report a case of tamoxifen associated macular hole with typical optical imaging and clinical features. A 53-year-old woman came to our department for gradual decrees of vision acuity in both eyes for 3 months after 30 months low-dosage-tamoxifen treatment as adjuvant treatment for invasive ductal breast carcinoma. Her best corrected visual acuity (BCVA) was 0.4 in the right eye and 0.12 in the left eye. Dilated fundus examination showed macular multiple, fine, crystalline deposits and small white points in retina of both eyes...
October 13, 2016: Photodiagnosis and Photodynamic Therapy
Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
H L M Tucker, K L Beaudry, C L M Parsons, S E Ellis, R M Akers
Prepubertal mammary development involves elongation and branching of ducts and stromal tissue remodeling. This process is closely linked with ovarian and pituitary hormones, growth factors, and local regulators. Accumulating evidence suggests that the myoepithelial cells also play a role in ductal development in addition to their well-recognized importance in the milk ejection reflex. Following reports that myoepithelial cells changed in correspondence with decreased mammary growth after ovariectomy of prepubertal heifers, we evaluated myoepithelial cells in mammary tissue collected from prepubertal heifers treated with the antiestrogen tamoxifen...
October 13, 2016: Journal of Dairy Science
Anna Kemp-Casey, Elizabeth E Roughead, Christobel Saunders, Frances Boyle, Max Bulsara, David B Preen
AIMS: To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. METHODS: We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 (n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy...
October 14, 2016: Asia-Pacific Journal of Clinical Oncology
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