50 results match your criteria pyrazole up-regulated

New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies.

Bioorg Chem 2020 05 12;98:103752. Epub 2020 Mar 12.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia. Electronic address:

Two new series of hybrid structures 16a-f and 19a-f containing 1,2,4-triazole moiety, pyrazole core with COX-2 pharmacophore and oxime as NO donor moiety were designed, synthesized and evaluated for anti-inflammatory, cytotoxic activities and NO release. All compounds were more selective for COX-2 isozyme especially the sulphamoyl derivatives (16b, 16e, 19b and 19e) had COX-2 selectivity indexes (S.I. Read More

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K3.1 channel mediates inflammatory signaling of pancreatic β cells and progression of type 2 diabetes mellitus.

FASEB J 2019 12 5;33(12):14760-14771. Epub 2019 Nov 5.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

Chronic islet inflammation is associated with development of type 2 diabetes mellitus (T2DM). Intermediate-conductance calcium-activated K (K3.1) channel plays an important role in inflammatory diseases. Read More

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December 2019

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure.

Exp Physiol 2019 12 15;104(12):1911-1928. Epub 2019 Nov 15.

Department of Physiology, School of Medicine, Marmara University, Istanbul, Turkey.

New Findings: What is the central question of this study? Could different hormonally active substances, including oestrogen receptor (ER) agonists, protect against oxidative brain damage and memory impairment induced by a single epileptic seizure in rats? If so, which signalling mechanisms are involved in their anti-inflammatory effects? What is the main finding and its importance? Chronic administration of oestrogen, progesterone, ER modulators/agonists or blockade of testosterone exhibited anti-inflammatory and antioxidant actions on single seizure-induced neuronal injury, while ER agonists additionally improved memory function and up-regulated CREB signalling and hippocampal GABA(A)α1 receptor density, suggesting that ERα or ERβ receptor activation may be beneficial in protecting against seizure-related oxidative brain injury and cognitive dysfunction.

Abstract: The susceptibility to epileptic seizures is dependent on sex as well as fluctuations in oestrogen levels, while exogenous oestrogen was shown to have no effect or to facilitate or to inhibit seizure activity. Oestrogen receptors (ERs) mediate antioxidant and anti-inflammatory actions in several inflammatory models, but the involvement of ERs in seizure-induced neuronal injury has not been evaluated previously. Read More

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December 2019

P8 nuclear receptor responds to acaricides exposure and regulates transcription of P450 enzyme in the two-spotted spider mite, Tetranychus urticae.

Comp Biochem Physiol C Toxicol Pharmacol 2019 Oct 26;224:108561. Epub 2019 Jun 26.

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China; Academy of Agricultural Sciences, Southwest University, Chongqing, China. Electronic address:

Spider mites are destructive arthropod pests on many crops and they have developed resistance to nearly all acaricides. In recent years, along with the application of high throughput sequencing, the molecular mechanisms of mite resistance had made a series of progress. But, the response in molecular level of mite exposure to acaricides, as well as the original mechanism of resistance development was still unclear. Read More

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October 2019

Oleanolic acid inhibits RANKL-induced osteoclastogenesis via ER alpha/miR-503/RANK signaling pathway in RAW264.7 cells.

Biomed Pharmacother 2019 Sep 5;117:109045. Epub 2019 Jun 5.

Qing Yuan Hospital of Traditional Chinese Medicine, 10 Qiao Bei Road, Qing yuan, Guangdong, 511500, China.

Oleanolic acid (OA) has recently become a research hotspot in the treatment of many human diseases, especially osteoporosis and arthritis. However, the mechanisms are not elucidated completely. We aimed to elucidate the target and the mechanism via which OA inhibited osteoclast differentiation. Read More

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September 2019

A Chemical Genetics Strategy that Identifies Small Molecules which Induce the Triple Response in Arabidopsis.

Molecules 2017 Dec 19;22(12). Epub 2017 Dec 19.

Department of Biotechnology Production, Faculty of Bioresource Sciences, Akita Prefectural University, 241-438, Shimoshinjo Nakano, Akita 010-0195, Japan.

To explore small molecules with ethylene-like biological activity, we conducted a triple response-based assay system for chemical library screening. Among 9600 compounds, we found -[(1,3,5-trimethyl-1-pyrazol-4-yl)methyl]--methyl-2-naphthalenesulfonamide () displayed promising biological activity on inducing a triple response in seedlings. Chemical synthesis and structure-activity relationship (SAR) analysis of analogues with different substitution patterns on the phenyl ring structure of the sulfonamide group indicated that 3,4-dichloro--methyl--(1,3,5-trimethyl-1-pyrazol-4-yl-methyl) benzenesulfonamide () exhibits the most potent biological activity. Read More

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December 2017

Oestrogen receptor β (ERβ) regulates osteogenic differentiation of human dental pulp cells.

J Steroid Biochem Mol Biol 2017 11 12;174:296-302. Epub 2017 Oct 12.

Department of Oral Biology, Wellcome Trust Brenner Building, St James University Hospital, University of Leeds, UK. Electronic address:

Estradiol (E) has many important actions in the tissues of the oral cavity. Disruption of E metabolism or alterations in systemic E concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E on bone physiology -especially maintenance of bone mineral density (BMD). Read More

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November 2017

Positive feedback role of TRPC3 in TNF-α-mediated vasogenic edema formation induced by status epilepticus independent of ET receptor activation.

Neuroscience 2016 Nov 10;337:37-47. Epub 2016 Sep 10.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea. Electronic address:

Brain-blood barrier (BBB) disruption results in vasogenic edema, which is involved in the pathogenesis of epilepsy. Following status epilepticus (SE), up-regulated transient receptor potential canonical channel-3 (TRPC3), a Ca-permeable cation channels in endothelial cells, is relevant to vasogenic edema formation in the rat piriform cortex. In addition, pyrazole-3 (Pyr-3, a TRPC3 inhibitor) attenuated SE-induced vasogenic edema. Read More

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November 2016

Differential Gene Expression Analysis of the Epacromius coerulipes (Orthoptera: Acrididae) Transcriptome.

J Insect Sci 2016 3;16. Epub 2016 May 3.

Heilongjiang Bayi Agricultural University,Daqing of Heilongjiang province, China,, 163319

Epacromius coerulipes (Ivanov) is one of the most widely distributed locusts. To date, the main methods to kill locusts still rely on chemical controls, which can result in the selection of locusts with resistance to chemical pesticides. Butene-fipronil is a new pesticide that was discovered by the structural modification of fipronil. Read More

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October 2016

Cryptotanshinone and wogonin up-regulate eNOS in vascular endothelial cells via ERα and down-regulate iNOS in LPS stimulated vascular smooth muscle cells via ERβ.

Arch Pharm Res 2016 Feb 20;39(2):249-258. Epub 2015 Oct 20.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China.

Phytoestrogens were widely used as natural alternatives to estrogen for treating cardiovascular diseases. They have been reported to have cardioprotective and anti-inflammatory response, but the mechanisms remain unclear. In this study, we found cryptotanshinone and wogonin exhibited phytoestrogenic property in an estrogen-responsive reporter assay. Read More

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February 2016

CNB-001, a novel pyrazole derivative mitigates motor impairments associated with neurodegeneration via suppression of neuroinflammatory and apoptotic response in experimental Parkinson's disease mice.

Chem Biol Interact 2014 Sep 1;220:149-57. Epub 2014 Jul 1.

Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.

Parkinson's disease (PD) is characterized by the progressive degeneration via apoptosis of nigrostriatal dopaminergic neurons associated with inflammation, resulting in behavioral anomalies. Therefore, an anti-apoptotic and anti-inflammatory regimen may be useful in treatment of PD. CNB-001, a novel pyrazole derivative of curcumin and cyclohexyl bisphenol A has superior biological properties than its parental compounds. Read More

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September 2014

Targeted inhibition of KCa3.1 attenuates TGF-β-induced reactive astrogliosis through the Smad2/3 signaling pathway.

J Neurochem 2014 Jul 27;130(1):41-49. Epub 2014 Mar 27.

Developmental Neurobiology Section, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.

Reactive astrogliosis, characterized by cellular hypertrophy and various alterations in gene expression and proliferative phenotypes, is considered to contribute to brain injuries and diseases as diverse as trauma, neurodegeneration, and ischemia. KCa3.1 (intermediate-conductance calcium-activated potassium channel), a potassium channel protein, has been reported to be up-regulated in reactive astrocytes after spinal cord injury in vivo. Read More

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G protein-coupled estrogen receptor1 (GPER1) may mediate Rho-kinase (ROCK-2) up-regulation in coronary endothelial cells.

Endocr Regul 2013 Apr;47(2):75-84

Department of Pharmacology, Mersin University, Mersin, Turkey.

Objective: Effect of estrogenic compounds and 17β-estradiol (E2), which induces endothelial cell motility, was investigated on ROCK-2 expression in rat coronary vascular endothelial cells (CVEC).

Methods: The CVEC were isolated from the heart of Wistar rats by collagenase (0.04%) and incubated with E2 (1-100 nM), estrogen receptor α (ERα) agonist: propyl pyrazole triol (PPT, 10 nM); ERβ agonists: (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN, 10 nM) and E2-conjugate with bovine serum albumin (E2-BSA, 1 nM); and GPER1 agonist: G1 (100 nM). Read More

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Osteopromotive activity of a novel pyrazole carboxamide derivative.

Future Med Chem 2013 Feb;5(2):125-34

Department of Periodontology, School of Stomatology, Shandong University, Jinan, 250012, P.R. China.

Aims: To investigate the effect of 1-(4-(tert-butyl)benzyl)-N-(4-methoxyphenyl)-3-phenyl-1H-pyrazole-5-carboxamide (Pyr-C) on the proliferation and osteogenic differentiation of MC3T3-E1 cells.

Materials & Methods: MTT and BrdU incorporation assay were used to determine cell survival and proliferation. The gene expression levels of osteogenic markers were determined using real-time PCR and ALP activity was detected. Read More

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February 2013

1,2,3,4,6-penta-O-galloyl-β-D-glucose protects PC12 Cells from MPP(+)-mediated cell death by inducing heme oxygenase-1 in an ERK- and Akt-dependent manner.

J Huazhong Univ Sci Technolog Med Sci 2012 Oct 18;32(5):737-745. Epub 2012 Oct 18.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Read More

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October 2012

Oestrogen receptor α agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats.

Int J Neuropsychopharmacol 2013 Jun 24;16(5):1071-82. Epub 2012 Sep 24.

Department of Pathology and Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ovariectomy is known as 'surgical menopause' with decreased levels of oestrogen in female rodents and its reported risks and adverse effects include cognitive impairment. In the brain, oestrogen exerts effects through its receptors, oestrogen receptor α (ERα) and β (ERβ). However, the role of ERα or ERβ in ovariectomy-induced cognitive impairment needs further investigation. Read More

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Synthesis and discovery of novel pyrazole carboxamide derivatives as potential osteogenesis inducers.

Arch Pharm (Weinheim) 2012 Nov 26;345(11):870-7. Epub 2012 Jul 26.

Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, PR China.

A series of novel N-aryl-3-aryl-1-arylmethyl-1H-pyrazole-5-carboxamide derivatives 4a-l was synthesized by the reaction of 3-aryl-1-arylmethyl-1H-pyrazole-5-carbonyl chloride with substituted aniline in good to excellent yields. Structures of the compounds were determined by IR, (1) H NMR, and HR-MS spectroscopy. The molecular structure was confirmed by the X-ray crystal analysis of one compound (4j) that was prone to crystallization. Read More

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November 2012

Peroxiredoxin III and sulfiredoxin together protect mice from pyrazole-induced oxidative liver injury.

Antioxid Redox Signal 2012 Nov 31;17(10):1351-61. Epub 2012 May 31.

Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.

Aims: To define the mechanisms underlying pyrazole-induced oxidative stress and the protective role of peroxiredoxins (Prxs) and sulfiredoxin (Srx) against such stress.

Results: Pyrazole increased Srx expression in the liver of mice in a nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent manner and induced Srx translocation from the cytosol to the endoplasmic reticulum (ER) and mitochondria. Pyrazole also induced the expression of CYP2E1, a primary reactive oxygen species (ROS) source for ethanol-induced liver injury, in ER and mitochondria. Read More

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November 2012

[Effects of daidzein on steroid receptor coactivator-1 expression in MC3T3-E1 cells and the mechanism].

Zhong Xi Yi Jie He Xue Bao 2011 Nov;9(11):1248-53

Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.

Objective: To investigate the roles of daidzein in the expressions of steroid receptor coactivator-1 (SRC-1) and nuclear receptor corepressor (NcoR) in MC3T3-E1 osteoblastic cells.

Methods: MC3T3-E1 cells were cultured in α-minimal essential medium (α-MEM) containing 2% fetal bovine serum and treated with various concentrations of daidzein (10(-9), 10(-7) and 10(-5) mol/L) or 17β-estradiol at 10(-8) mol/L for 3 d. The protein levels of SRC-1 and NcoR in MC3T3-E1 cells were determined by Western blotting. Read More

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November 2011

Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function.

J Neuroendocrinol 2012 Jan;24(1):236-48

Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Pharmaceutical Sciences Center, Los Angeles, CA 90089, USA.

The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. Read More

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January 2012

Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice.

Eur J Pharmacol 2011 Oct 13;668(1-2):184-9. Epub 2011 Jul 13.

Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Facultad de Medicina C/ Julián Clavería, 6. 33006 Oviedo, Asturias, Spain.

The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms. Several reports have described the up-regulation of spinal cannabinoid CB(2) receptors in neuropathic settings together with the analgesic effects derived from their activation. Besides, we have recently reported in two murine bone cancer models that the intrathecal administration of cannabinoid CB(2) receptor agonists completely abolishes hyperalgesia and allodynia, whereas spinal cannabinoid CB(2) receptor expression remains unaltered. Read More

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October 2011

Intermediate-conductance Ca2+-activated K+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia.

J Pharmacol Exp Ther 2011 Aug 20;338(2):528-36. Epub 2011 May 20.

Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Muzuhoku, Nagoya 467-8603, Japan.

Recently, a new experimental stromal hyperplasia animal model corresponding to clinical benign prostatic hyperplasia (BPH) was established. The main objective of this study was to elucidate the roles of the intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) in the implanted urogenital sinus (UGS) of stromal hyperplasia BPH model rats. Read More

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Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract.

Gastroenterology 2011 Jul 16;141(1):237-48, 248.e1. Epub 2011 Apr 16.

Dipartimento di Medicina Interna, Università Tor Vergata, Rome, Italy.

Background & Aims: The pathogenesis of inflammatory bowel disease (IBD) is believed to involve an altered balance between effector and regulatory T cells. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that mediates the toxicity of dioxins, controls T-cell responses. We investigated the role of AhR in inflammation and pathogenesis of IBD in humans and mouse models. Read More

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Estrogens promote invasion of prostate cancer cells in a paracrine manner through up-regulation of matrix metalloproteinase 2 in prostatic stromal cells.

Endocrinology 2011 Mar 19;152(3):773-81. Epub 2011 Jan 19.

Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071, China.

Accumulating evidence suggests an enhancing effect of estrogens on prostate cancer (PCa) progression. Matrix metalloproteinase 2 (MMP2), which plays an important role in prostate cancer invasion, is mainly expressed in prostatic stromal cells (PrSC). Here we show that estradiol (E(2)) treatment up-regulates MMP2 production in PrSC, which promotes PCa cell invasion in a paracrine manner. Read More

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Obesity up-regulates intermediate conductance calcium-activated potassium channels and myoendothelial gap junctions to maintain endothelial vasodilator function.

J Pharmacol Exp Ther 2010 Nov 29;335(2):284-93. Epub 2010 Jul 29.

Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.

The mechanisms involved in altered endothelial function in obesity-related cardiovascular disease are poorly understood. This study investigates the effect of chronic obesity on endothelium-dependent vasodilation and the relative contribution of nitric oxide (NO), calcium-activated potassium channels (K(Ca)), and myoendothelial gap junctions (MEGJs) in the rat saphenous artery. Obesity was induced by feeding rats a cafeteria-style diet (∼30 kJ as fat) for 16 to 20 weeks, with this model reflecting human dietary obesity etiology. Read More

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November 2010

Genome-wide expression profiling revealed peripheral effects of cannabinoid receptor 1 inverse agonists in improving insulin sensitivity and metabolic parameters.

Mol Pharmacol 2010 Sep 7;78(3):350-9. Epub 2010 Jun 7.

Department of Molecular Profiling, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.

Inhibition of cannabinoid receptor 1 (CB1) has shown efficacy in reducing body weight and improving metabolic parameters, with the effects correlating with target engagement in the brain. The peripheral effects of inhibiting the CB1 receptor has been appreciated through studies in diet-induced obese and liver-specific CB1 knockout mice. In this article, we systematically investigated gene expression changes in peripheral tissues of diet-induced obese mice treated with the CB1 inverse agonist AM251 [1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl)pyrazole-3-carboxamide]. Read More

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September 2010

Chronic inhibition of nitric-oxide synthase potentiates endothelium-dependent contractions in the rat aorta by augmenting the expression of cyclooxygenase-2.

J Pharmacol Exp Ther 2010 Aug 5;334(2):373-80. Epub 2010 May 5.

Department of Pharmacology and Pharmacy, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.

Acute inhibition of nitric-oxide synthase (NOS) unmasks the release of endothelium-derived contracting factors (EDCFs). The present study investigated whether chronic inhibition of NOS modulates endothelium-dependent contractions. Eighteen-week-old male Sprague-Dawley rats were treated by daily gavage for 6 weeks with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (60 mg/kg) or vehicle (distilled water; 1 ml/kg). Read More

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Inhibition of mammary tumor growth by estrogens: is there a specific role for estrogen receptors alpha and beta?

Breast Cancer Res Treat 2010 Oct 11;123(3):709-24. Epub 2009 Dec 11.

Laboratory of Hormonal Carcinogenesis, Institute of Experimental Biology and Medicine, National Research Council of Argentina (CONICET), 1428 Buenos Aires, Buenos Aires, Argentina.

To evaluate the extent to which each estrogen receptor (ER) subtype contributes to the stimulation or to the inhibition of mammary tumor growth, we evaluated the effects of specific agonists in MC4-L2 cells, which are stimulated by 17β-estradiol (E(2)), and in mammary carcinomas of the MPA mouse breast cancer model, which are inhibited by E(2). Both express ERα and ERβ. In MC4-L2 cells, 4,4',4"-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT; ERα agonist) and (4-hydroxy-phenyl)-propionitrile (DPN; ERβ agonist) stimulated cell proliferation, whereas the opposite occurred in C4-HI primary cultures. Read More

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October 2010

Structure-activity relationships and cancer-cell selective toxicity of novel inhibitors of glioma-associated oncogene homologue 1 (Gli1) mediated transcription.

J Med Chem 2009 Jul;52(14):4277-87

St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

We report novel inhibitors of Gli1-mediated transcription as potential anticancer agents. Focused chemical libraries were designed and assessed for inhibition of functional cell-based Gli1-mediated transcription and selective toxicity toward cancer cells. The SAR was revealed, and the selectivity of the lead compounds' inhibition of Gli1-mediated transcription over that of Gli2 was determined. Read More

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CsPLDalpha1 and CsPLDgamma1 are differentially induced during leaf and fruit abscission and diurnally regulated in Citrus sinensis.

J Exp Bot 2008 17;59(13):3729-39. Epub 2008 Sep 17.

University of Florida/IFAS, Horticultural Sciences Department, Citrus Research and Education Center, 700 Experiment Station Road, Lake Alfred, FL 33850, USA.

Understanding leaf and fruit abscission is essential in order to develop strategies for controlling the process in fruit crops. Mechanisms involved in signalling leaf and fruit abscission upon induction by abscission agents were investigated in Citrus sinensis cv. 'Valencia'. Read More

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November 2008