Academic literature on the topic 'MCSF receptor'
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Journal articles on the topic "MCSF receptor"
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Azuma, C., F. Saji, T. Kimura, Y. Tokugawa, M. Takemura, Y. Samejima, and O. Tanizawa. "Steroid hormones induce macrophage colony-stimulating factor (MCSF) and MCSF receptor mRNAs in the human endometrium." Journal of Molecular Endocrinology 5, no. 2 (October 1990): 103–8. http://dx.doi.org/10.1677/jme.0.0050103.
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ABSTRACT We investigated the biological effects of sex-steroid hormones, secreted from the corpus luteum and placenta, on the induction of mRNAs encoding macrophage colony-stimulating factor (MCSF) and c-fms proto-oncogene (MCSF receptor) in human endometrium. RNA was extracted from the placenta and endometrium of both pregnant and non-pregnant women, and Northern blot analysis was performed on poly(A)+ RNA using MCSF or c-fms proto-oncogene cDNA as the probe. Results showed: (1) that MCSF mRNA was expressed in the placenta and endometrium of the pregnant uterus, (2) that c-fms proto-oncogene mRNA was also expressed in the placenta and endometrium of the pregnant uterus, and (3) that exogenous sex-steroid hormones could induce the expression of MCSF and c-fms proto-oncogene mRNAs in the endometrium of non-pregnant women. These results indicate that sex-steroid hormones secreted by the corpus luteum and/or placenta influence endometrial and placental growth and differentiation via a mechanism of action involving local production of MCSF and its receptor.
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Frangogiannis, Nikolaos G., Leonardo H. Mendoza, Guofeng Ren, Spyridon Akrivakis, Peggy L. Jackson, Lloyd H. Michael, C. Wayne Smith, and Mark L. Entman. "MCSF expression is induced in healing myocardial infarcts and may regulate monocyte and endothelial cell phenotype." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 2 (August 2003): H483—H492. http://dx.doi.org/10.1152/ajpheart.01016.2002.
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Myocardial infarction is associated with the rapid induction of mononuclear cell chemoattractants that promote monocyte infiltration into the injured area. Monocyte-to-macrophage differentiation and macrophage proliferation allow a long survival of monocytic cells, critical for effective healing of the infarct. In a canine infarction-reperfusion model, newly recruited myeloid leukocytes were markedly augmented during early reperfusion (5–72 h). By 7 days, the number of newly recruited myeloid cells was reduced, and the majority of the inflammatory cells remaining in the infarct were mature macrophages. Macrophage colony-stimulating factor (MCSF) is known to facilitate monocyte survival, monocyte-to-macrophage conversion, and macrophage proliferation. We demonstrated marked induction of MCSF mRNA in ischemic segments persisting for at least 5 days after reperfusion. MCSF expression was predominantly localized to mature macrophages infiltrating the infarcted myocardium; the expression of the MCSF receptor, c-Fms, a protein with tyrosine kinase activity, was found in these macrophages but was also observed in a subset of microvessels within the infarct. Many infarct macrophages expressed proliferating cell nuclear antigen, a marker of proliferative activity. In vitro MCSF induced monocyte chemoattractant protein-1 synthesis in canine venous endothelial cells. MCSF-induced endothelial monocyte chemoattractant protein-1 upregulation was inhibited by herbimycin A, a tyrosine kinase inhibitor, and by LY-294002, a phosphatidylinositol 3′-kinase inhibitor. We suggest that upregulation of MCSF in the infarcted myocardium may have an active role in healing not only through its effects on cells of monocyte/macrophage lineage, but also by regulating endothelial cell chemokine expression.
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Wang, Tiehui, Tomoya Kono, Milena M. Monte, Haruka Kuse, Maria M. Costa, Hiroki Korenaga, Tanja Maehr, Mansourah Husain, Masahiro Sakai, and Christopher J. Secombes. "Identification of IL-34 in teleost fish: Differential expression of rainbow trout IL-34, MCSF1 and MCSF2, ligands of the MCSF receptor." Molecular Immunology 53, no. 4 (April 2013): 398–409. http://dx.doi.org/10.1016/j.molimm.2012.09.008.
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Llewellyn, Heather P., Vishal S. Vaidya, Zhenyu Wang, Qinghai Peng, Craig Hyde, David Potter, Jianying Wang, et al. "Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans." Toxicological Sciences 181, no. 1 (January 23, 2021): 23–34. http://dx.doi.org/10.1093/toxsci/kfab003.
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Abstract Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective of this study was to evaluate the diagnostic performance of promising biomarkers of liver injury—glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), and microRNA-122 (miR-122) in comparison to the traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually and as a multivariate model in a cohort of acetaminophen overdose (n = 175) subjects and were further tested in cohorts of healthy adults (n = 135), patients with liver damage from various causes (n = 104), and patients with damage to the muscle (n = 74), kidney (n = 40), gastrointestinal tract (n = 37), and pancreas (n = 34). In the acetaminophen cohort, a multivariate model with GLDH, K18, and miR-122 was able to detect DILI more accurately than individual biomarkers alone. Furthermore, the three-biomarker model could accurately predict patients with liver injury compared with healthy volunteers or patients with damage to muscle, pancreas, gastrointestinal tract, and kidney. Expression of K18, GLDH, and miR-122 was evaluated using a database of transcriptomic profiles across multiple tissues/organs in humans and rats. K18 mRNA (Krt18) and MiR-122 were highly expressed in liver whereas GLDH mRNA (Glud1) was widely expressed. We performed a comprehensive, comparative performance assessment of 7 promising biomarkers and demonstrated that a 3-biomarker multivariate model can accurately detect liver injury.
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Gu, Hanjie, Bo Wang, Jiaojiao He, and Yonghua Hu. "Macrophage colony stimulating factor (MCSF) of Japanese flounder (Paralichthys olivaceus): Immunoregulatory property, anti-infectious function, and interaction with MCSF receptor." Developmental & Comparative Immunology 116 (March 2021): 103920. http://dx.doi.org/10.1016/j.dci.2020.103920.
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JARRAR, Hala, Damla ÇETİN ALTINDAL, and Menemşe GÜMÜŞDERELİOĞLU. "The inhibitory effect of melatonin on osteoclastogenesis of RAW 264.7 cells in low concentrations of RANKL and MCSF." TURKISH JOURNAL OF BIOLOGY 44, no. 6 (December 14, 2020): 427–36. http://dx.doi.org/10.3906/biy-2007-85.
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RAW 264.7 cells are one of the most recommended cell lines for investigating the activity and differentiation of osteoclasts. These cells differentiate into osteoclasts in the presence of two critical components: receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (MCSF). Melatonin (MEL) hormone has recently become one of the small molecules used in the field of bone regeneration and bone disease treatment, as it has the ability to inhibit the differentiation of osteoclasts directly by suppression of the NF-κB signaling pathway. The main aim of the current study is to determine sufficient RANKL/MCSF concentrations for differentiation of the cells to osteoclasts and to describe the repressive effect of MEL on the osteoclastogenesis of these cells. In this regard, it was found that 10 ng/mL of RANKL- and MCSF-containing medium is suitable for inducing osteoclastogenesis of the cells. In addition, melatonin at doses in the range of 100–1000 μM does not have a cytotoxic effect. Subsequently, results of tartrate resistant acid phosphatase (TRAP) activity, TRAP staining, and relative expressions of cathepsin K, nuclear factor of activated T cells one (NFATC1), and TRAP genes showed a suppressive effect of MEL —especially 800 μM— on RANKL-induced osteoclastogenesis of these cells.
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Langer, Thomas M., Suzanne E. Neumueller, Emma Crumley, Nicholas J. Burgraff, Sawan Talwar, Matthew R. Hodges, Lawrence Pan, and Hubert V. Forster. "Ventilation and neurochemical changes during µ-opioid receptor activation or blockade of excitatory receptors in the hypoglossal motor nucleus of goats." Journal of Applied Physiology 123, no. 6 (December 1, 2017): 1532–44. http://dx.doi.org/10.1152/japplphysiol.00592.2017.
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Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally ( n = 5) or bilaterally ( n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO; 100 µM) decreased pulmonary ventilation (V̇i), breathing frequency ( f), and genioglossus (GG) muscle activity but did not alter neuromodulators measured in the effluent mCSF. However, neither unilateral dialysis of a broad spectrum muscarinic receptor antagonist (atropine; 50 mM) nor unilateral or bilateral dialysis of a mixture of excitatory receptor antagonists altered V̇i or GG activity, but all of these did increase HMN serotonin (5-HT) levels. Finally, during night studies, DAMGO and excitatory receptor antagonist decreased ventilatory variables during NREM sleep but not during wakefulness. These findings contrast with previous dialysis studies in the ventral respiratory column (VRC) where unilateral DAMGO or atropine dialysis had no effects on breathing and bilateral DAMGO or unilateral atropine increased V̇i and f and decreased GABA or increased 5-HT, respectively. Thus we conclude that the mechanisms of compensatory neuromodulation are less robust in the HMN than in the VRC under physiological conditions in adult goats, possibly because of site differences in the underlying mechanisms governing neuromodulator release and consequently neuronal activity, and/or responsiveness of receptors to compensatory neuromodulators. NEW & NOTEWORTHY Activation of inhibitory µ-opioid receptors in the hypoglossal motor nucleus decreased ventilation under physiological conditions and did not affect neurochemicals in effluent dialyzed mock cerebral spinal fluid. These findings contrast with studies in the ventral respiratory column where unilateral [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO) had no effects on ventilation and bilateral DAMGO or unilateral atropine increased ventilation and decreased GABA or increased serotonin, respectively. Our data support the hypothesis that mechanisms that govern local compensatory neuromodulation within the brain stem are site specific under physiological conditions.
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Langer, Thomas M., Suzanne E. Neumueller, Emma Crumley, Nicholas J. Burgraff, Sawan Talwar, Matthew R. Hodges, Lawrence Pan, and Hubert V. Forster. "State-dependent and -independent effects of dialyzing excitatory neuromodulator receptor antagonists into the ventral respiratory column." Journal of Applied Physiology 122, no. 2 (February 1, 2017): 327–38. http://dx.doi.org/10.1152/japplphysiol.00619.2016.
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Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-Bötzinger complex region] of awake goats increased pulmonary ventilation (V̇i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V̇i or f, but increases local SP. Herein, we tested hypotheses that 1) local compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of goats will not differ between anesthetized and awake states; and 2) bilateral dialysis of the triple cocktail of antagonists into the VRC of awake goats will not alter V̇i or f, but will increase local excitatory neuromodulators. Through microtubules implanted into the VRC of goats, probes were inserted to dialyze mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists. We found 1) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared with isoflurane anesthesia, but V̇i and f only increased while awake; and 2) dialyses of the triple cocktail of antagonists increased V̇i, f, 5-HT, and SP (<0.05) during both day and night studies. We conclude that the mechanisms governing local neuromodulator levels are state independent, and that bilateral excitatory receptor blockade elicits an increase in breathing, presumably due to a local, (over)compensatory neuromodulator response. NEW & NOTEWORTHY The two major findings are as follows: 1) during unilateral dialysis of 50 mM atropine into the ventral respiratory column to block excitatory muscarinic receptor activity, a compensatory increase in other neuromodulators was state independent, but the ventilatory response appears to be state dependent; and 2) the hypothesis that absence of decreased V̇i and f during unilateral dialysis of excitatory receptor antagonists was due to compensation by the contralateral VRC was not supported by findings herein.
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Chen, Haiming, Mingjie Li, Eric Sanchez, Abigail Gillespie, Cathy Wang, Tiffany Lee, Suzie Vardanyan, et al. "Crosslinking of Fc Gamma-Rllb and Fc Epsilon-RI Binding Peptides Inhibits Osteoclast Formation in Multiple Myeloma through Inactivation of the ITAM Signaling Pathway." Blood 126, no. 23 (December 3, 2015): 2995. http://dx.doi.org/10.1182/blood.v126.23.2995.2995.
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Abstract Introduction: Overactivity of osteoclasts resulting in bone destruction is a hallmark of multiple myeloma (MM). Receptor for activation of NF-kB ligand (RANKL) and monocyte colony stimulating factor (MCSF) signaling pathways both promote proliferation and survival of the precursors of the osteoclast lineage, and have been widely investigated in MM. The third pathway involved in osteoclast differentiation is the immunoreceptor tyrosine-based activation motif (ITAM) with c-Fms signaling. ITAM and its inhibitor ITIM provide the basis for two opposed signaling modules that duel for control of osteoclast formation. Human monocyte/macrophage expresses the low-affinity FcγRIIb and high-affinity Fcε receptor 1 (FcεRI). Both receptors mediate Syk phosphorylation to activate or inactivate downstream ITAM or ITIM signaling molecules. In this study, we determined the effects of an IgG(CH2-CH3) and IgE(CH2-CH3-CH4) fusion protein that activates the ITIM inhibitory pathway on downstream signaling of Syk and osteoclast formation in monocytes from MM patients. Methods: We constructed IgG(CH2-CH3) with an IgE(CH2-CH3-CH4) fusion protein using standard cloning techniques. We evaluated the fusion protein on osteoclast formation using cells from either human monocytes isolated from MM patients' peripheral blood mononuclear cells (PBMCs) or bone marrow (BM) MCs with an anti-CD14 micro-bead affinity column and magnetic bead selection (Miltenyi Biotec, Auburn, CA). The monocytes were cultured on slide-culture dishes (2 X 105 cells/well). The cells were treated with the fusion protein or with IgE or IgG and subsequently treated with 50ng/ml RANKL (receptor for activation of nuclear factor kB and 10ng/ml MCSF (monocyte colony stimulating factor) in order to stimulate osteoclast formation at the beginning of the culture and during a medium change after 3 days with the same amount of growth factors added. The cells were fixed for tartrate resistant acid phosphatase (TRAP)-staining assay on day 21. To investigate ITIM signaling pathway we determined Syk phosphorylation of monocytes treated or without treated with fusion protein by Western blot analysis. Results: We found that in a concentration-dependent fashion, the fusion protein inhibited osteoclast cell formation from CD14+ MCs from PB or BM exposed to RANKL and MCSF. We further analyzed the effects on the FcγRIIb-SHIP signaling pathway in monocytes induced with 50ng/ml RANKL and 10ng/ml MCSF following exposure to fusion protein or control IgG or IgE. The results showed that the monocytes showed markedly lower Syk phosphorylation following exposure to the fusion protein (100-200ng/ml). There was no change of Syk phosphorylationl in monocytes treated with IgG or IgE or IgG with IgE. Conclusions: The results of our study show that intact human IgG or IgE does not affect the ITAM or ITIM signaling pathways. However, a fusion protein consisting of IgG(CH2-CH3) with IgE(CH2-CH3-CH4) showed the ability to activate the ITIM inhibition pathway through FcγRIIb to reduce osteoclast formation. Thus, blockage of ITAM may be treating novel treatment for preventing bone loss for MM patients. Disclosures No relevant conflicts of interest to declare.
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Azuma, C., F. Saji, T. Kimura, Y. Tokugawa, M. Takemura, M. Miki, M. Ono, and O. Tanizawa. "The gene expressions of macrophage colony-stimulating factor (MCSF) and MCSF receptor in the human myometrium during pregnancy: Regulation by sex steroid hormones." Journal of Steroid Biochemistry and Molecular Biology 39, no. 6 (December 1991): 883–88. http://dx.doi.org/10.1016/0960-0760(91)90345-6.
Full textDissertations / Theses on the topic "MCSF receptor"
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Zhao, Bo. "Local mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor (MCSF-1), and its receptor, c-fms, on rabbit heart valves in the early phase after atrioventricular valve surgery and Staphylococcus aureus bacteremia." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972046437.
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Araujo, Fabiano Conde. "Expressão e localização das proteínas c-Fos e receptor de estrogênio beta no testículo humano." Universidade Federal de Minas Gerais, 2006. http://hdl.handle.net/1843/MCSC-78PPEN.
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The testes are glands with endocrine and exocrine functions, the latter being characterized by sperm formation, or spermatogenesis. This is under the control of a complex system involving endocrine and paracrine signalization. In view of an interrelationship between the expression of c-Fos and estrogen receptor beta (ERbeta) proteins, this investigation evaluated the expression of the protooncogene c-fos and the immunolocalization of c-Fos, phosphorylated c-Fos and ERbeta proteins in the human testis. Testis tissue was obtained from 12 men undergoing orchiectomy as a treatment for prostate cancer. These patients had received no hormonal, chemo or radiation therapy before the operations. Tissues were stained by immunohistochemistry using the avidin-biotin-peroxidase method, and c-fos RNAm expression was assessed with reverse transcriptase- polymerase chain reaction (RT-PCR). The protooncogene c-fos was expressed in the human testis and both forms of c-Fos proteins were immunoreactive, mainly in germ cells (spermatogonia, spermatocytes and spermatids) and Sertoli cells. ERbeta was primarily present in somatic cells (Leydig, Sertoli and myofibrillar cells). Based on these results, we hypothesized two mechanisms for estrogen actions over spermatogenesis. The first would be mediated by Sertoli cells, where estrogens could alter either gene expression or the transcriptional activity of c-Fos protein. The other is an indirect mechanism, representing the interrelationship between somatic and germ cells. Somatic cells, under estrogen influence, could modify germ cell functions by paracrine/juxtacrine factors, which would change gene expression or the transcriptional activity of c-Fos protein.Os testículos são glândulas com função endócrina e exócrina, sendo que esta última se caracteriza pela formação de gametas masculinos, ou seja, a espermatogênese. Esta se encontra sob a influência de um complexo sistema de sinalização endócrina (sistêmica e parácrina). Considerando uma possível inter-relação entre as proteínas c-Fos e receptor de estrogênios beta (ER-beta), este trabalho verificou a expressão do proto-oncogene c-fos e a imunolocalização das proteínas c-Fos, c-Fos fosforilada e ER-beta no parênquima testicular humano. A amostra foi constituída por 12 homens férteis, portadores de adenocarcinoma prostático, com indicação terapêutica de bloqueio hormonal cirúrgico pela orquiectomia. Nenhum destes havia sido previamente submetido a tratamento hormonal, quimioterapia ou radioterapia. O material foi processado para o estudo imunohistoquímico com o método da avidina-biotina-peroxidase e avaliação da expressão gênica por transcrição reversa e reação em cadeia da polimerase (RT-PCR). A expressão do proto-oncogene c-fos foi comprovada no testículo humano, e as proteínas c-Fos e c-Fos fosforilada foram localizadas principalmente no epitélio seminífero, tanto nas células germinativas (espermatogônias, espermatócitos e espermátides) quanto nas células de Sertoli. O ER-beta foi expresso principalmente em células somáticas (células de Leydig, Sertoli e mióides). A distribuição encontrada das proteínas c-Fos e ER-beta nos permite supor uma inter-relação entre estas; seja pela ação estrogênica na célula de Sertoli, induzindo a expressão local de c-fos, seja indiretamente, pelos efeitos que o estímulo estrogênico sobre as células somáticas poderia ter sobre a expressão de c-fos no epitélio germinativo.
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Moura, Marina Matos de. "Reflexos cardiovasculares em camundongos com alteração na expressão do receptor da Angiotensina-(1-7), MAS." Universidade Federal de Minas Gerais, 2007. http://hdl.handle.net/1843/MCSC-7C6TJK.
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Several substances may modulate reflex cardiovascular activity, such reninangiotensin system peptides. The tecidual renin-angiotensin system is involved in regulation of cardiovascular structures and functions and, consequently in long-term blood pressure control, contributing in a significant way to maintenance and development of high
peripheral resistance and vascular hypereactivity found in the essential and experimental hypertension. Studies about the renin-angiotensin influences on neural control of BP show that Ang II reduces baroreflex sensitivity, reduces the Bezold-Jarisch reflex sensitivity and increases the chemoreflex responses. Because known that several Ang-(1-7) actions are opposite to Ang II actions, mainly about cardiac and vascular control, as well baroreflex sensibility, it is reasonable to suppose that the heptapeptide Ang-(1-7) acting on Ang-(1-7)s Mas receptor, also to take part of the Bezold-Jarisch reflex and the chemoreflex. To have the opportunity to use genetic change animals as for Mas receptor expression, we asses the hypothesis that Ang-(1-7), via Mas receptor, to contribute for the reflex cardiovascular modulation, in mice with Mas receptor deletion ou Mas receptor overexpression at brain. In sequence, considering the evidences of counter-regulatory actions between Ang II/Ang-(1-7), and the possibility to interaction between Mas/AT1
receptors, we also to asses the hypothesis that Mas receptor deletion to change the Ang II effects, because the absence to counter-regulatory effects to Ang-(1-7), via Mas receptor.
We use control (Wild-Type) and Mas receptor expression changes mice, Knockout Mas receptor mice (KO-Mas) and overexpression in brain Mas receptor (NSE-Mas), with background C57BL6J and FVBN. We showed in this study, through genetic manipulation of the Mas receptor expression, the effective participation of Angiotensin-(1-7) in the xiii cardiovascular control. Mas knockout mice (FVBN background) awake show high
basal MAP values in comparison with control mice (118 ± 1 vs. 109 ± 2 mmHg, p<0.01), but not show significant changes in basal HR values (615 ± 30 vs. 648 ± 13 bpm). The deletion of Mas receptor decreases baroreflex bradycardia (0.78 ± 0.44 vs. 1.3 ± 0.14 ms/mmHg, p<0.05), increases baroreflex tachycardia (1.63 ± 0.4 vs. 0.80 ± 0.13ms/mmHg, p<0.05), decreases the bradycardic and hypotensive response of Bezold-
Jarisch reflex (-17 ± 5 vs. -45 ± 6 mmHg e -212 ± 36 vs. -391 ± 29 bpm, FB 0.5Ng/5Nl, p<0.01) and increases the reflex responses observed by chemoreflex stimulation (20 ± 3vs. 12 ± 0.8 mmHg e -250 ± 74 vs. -52 ± 26 bpm, KCN 2.5Ng/5Nl, p<0.05) in awake FVBN background mice. In accordance with changes describe, we showed that Mas knockout
receptor mice had reduce tachycardic effect produce by methilatropine administration (23 ±4 vs. 70 ± 19 bpm, p<0.05) and increase bradycardic effect induced by atenolol administration (-181 ± 10 vs. -115 ± 23 bpm, p<0.05). When we measure transgenic mice with overexpression of Mas receptor in brain (NSE-Mas), demonstrate that Ang-(1-7), acting in CNS, participate of basal and reflex cardiovascular variables control. The Mas
receptor overexpression in brain mice induces increases of basal MAP (116 ± 3 vs. 109 ± 2 mmHg, p<0.05) and not change basal HR values (641 ± 18 vs. 648 ± 13 bpm). About bradycardic barorefelx response, we showed that Mas receptor overexpression in brain promoves increase this response (2.03 ± 0.33 vs. 1.3 ± 0.14 ms/mmHg, p<0.05). After A-
779, Ang-(1-7) antagonist, ICV administration, despite did not show significant changes in MAP and HR basal values in NSE-Mas and control mice, we show that bradycardic (1.17 ± 0.14 vs. 1.92 ± 0.37 ms/mmHg, p<0.05), and tachycardic (0.49 ± 0.11 vs. 0.94 ± 0.32 ms/mmHg, p<0.01), baroreflex responses were significantly decrease only in control FVBN
background awake mice. In this study, we highlight the important interaction Ang-(1-7)/Mas couter-balancing the classic actions of Ang II/AT1 in the cardiac autonomic activity maintenance, as reflexes and basal cardiovascular responses control. These results join with literature reports, contribute to physiologic relevancy of Ang-(1-7), acting on the Mas
receptor, in the cardiovascular function control.Várias substâncias podem modular a atividade cardiovascular reflexa, entre elas os peptídeos do SRA. O SRA tecidual está envolvido na regulação da estrutura e função cardiovascular e, consequentemente no controle a longo prazo da PA, contribuindo de forma significativa para o desenvolvimento e manutenção da alta resistência periférica e hiper-reatividade vascular encontradas em várias formas de hipertensão essencial e experimental. Os estudos sobre a influência do SRA sobre o controle neural da PA demonstram que a Ang II diminui a sensibilidade do barorreflexo, diminui a sensibilidade do reflexo de Bezold-Jarisch e facilita a resposta quimiorreflexa. Sabendo-se que várias ações da Ang-(1-7) são opostas àquelas observadas pela Ang II, principalmente no que se refere aos seus efeitos sobre o controle cardíaco e vascular, bem como sobre a sensibilidade barorreflexa, é razoável supor que o heptapeptídeo Ang-(1-7), agindo em seu receptor Mas, também participe da regulação do reflexo Bezold-Jarisch e do quimiorreflexo. Com a possibilidade de utilizar animais geneticamente modificados quanto à expressão do receptor Mas, avaliamos a hipótese de que a Ang-(1-7), via receptor Mas, contribui para a modulação das respostas cardiovasculares reflexas, em camundongos com deleção do receptor Mas ou com superexpressão deste receptor no cérebro. Na seqüência, considerando as evidências de ações contra-regulatórias entre Ang II/Ang-(1-7), e a possibilidade de interação dos receptores Mas/AT1, também avaliamos em nosso estudo a hipótese de a deleção do receptor Mas alterar os efeitos mediados pela Ang II, em decorrência da ausência dos efeitos contra-regulatórios mediados pela Ang-(1-7), via receptor Mas. Utilizamos camundongos controle (Wild Type) e com alterações da expressão do receptor da Ang-(1-7), receptor Mas: com deleção do receptor da Ang-(1-7) x Mas (KO-Mas) e com superexpressão deste receptor no cérebro (NSE-Mas), de duas linhagens diferentes (C57BL6J e FVBN). Demonstramos neste estudo, através da utilização de camundongos submetidos à manipulação da expressão gênica do receptor Mas, a efetiva participação da Ang-(1-7) via receptor Mas na manutenção e controle das variáveis cardiovasculares. Camundongos com deleção do receptor Mas da linhagem FVBN não anestesiados apresentam valores de PAM basais elevados em relação aos animais controle (118 ± 1 vs. 109 ± 2 mmHg, p<0.01), mas não apresentam alterações significativas nos valores basais de FC (615 ± 30 vs. 648 ± 13 bpm). A deleção do receptor Mas atenua a bradicardia barorreflexa (0.78 ± 0.44 vs. 1.3 ± 0.14 ms/mmHg, p<0.05), facilita a taquicardia barorreflexa (1.63 ± 0.4 vs. 0.80 ± 0.13 ms/mmHg, p<0.05), atenua as respostas hipotensora e bradicárdica que constituem o reflexo de Bezold-Jarisch (-17 ± 5 vs. -45 ± 6 W PAM, mmHg, e -212 ± 36 vs. -391 ± 29 W FC, bpm, FB 0.5Ng/5Nl, p<0.01) e facilita as respostas reflexas observadas após estimulação do quimiorreflexo (20 ± 3 vs. 12 ± 0.8 W PAM, mmHg, e -250 ± 74 vs. -52 ± 26 W FC, bpm, KCN .5Ng/5Nl, p<0.05) em camundongos da linhagem FVBN, não anestesiados. Em acordo com as alterações descritas, observamos que a deleção do receptor Mas reduz o efeito taquicárdico promovido pela administração de metilatropina (23 ± 4 vs. 70 ± 19 W FC, bpm, p<0.05) e aumenta o efeito bradicárdico promovido pela administração de atenolol (-181 ± 10 vs. - 115 ± 23 W FC, bpm, p<0.05). Utilizando camundongos transgênicos que superexpressam o receptor Mas no cérebro (NSE-Mas), observamos que a Ang-(1-7), agindo no SNC, participa do controle das variáveis cardiovasculares basais e reflexas. A superexpressão do receptor Mas no cérebro induz elevação dos valores basais de PAM (116 ± 3 vs. 109 ± 2 mmHg, p<0.05) e não altera os valores basais de FC (641 ± 18 vs. 648 ± 13 bpm). Com xi relação à resposta barorreflexa, observamos que a superexpressão do receptor Mas no cérebro promove facilitação da bradicardia barorreflexa (2.03 ± 0.33 vs. 1.3 ± 0.14 ms/mmHg, p<0.05). Para avaliar a contribuição da Ang-(1-7) endógena, administramos ICV o antagonista da Ang-(1-7), A-779, e apesar de não observarmos alterações significativas nos valores de PAM e FC basais dos camundongos NSE-Mas e controle, observamos que as respostas bradicárdica (1.17 ± 0.14 vs. 1.92 ± 0.37 ms/mmHg, p<0.05), e taquicárdica (0.49 ± 0.11 vs. 0.94 ± 0.32 ms/mmHg, p<0.01), barorreflexas foram significativamente reduzidas nos camundongos controle. Considerando os resultados do presente estudo, destacamos a importância da interação Ang-(1-7)/Mas contrabalanceando as ações clássicas da Ang II/AT1 para a manutenção da atividade autonômica cardíaca, assim como na modulação das respostas cardiovasculares reflexas e na manutenção dos valores basais de PA. Estes resultados associados aos dados da literatura, corroboram a relevância fisiológica da Ang-(1-7), agindo via receptor Mas, no controle da função cardiovascular.
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Santos, Sergio Henrique Sousa. "Avaliação dos distúrbios metabólicos produzidos pela deleção genética do receptor de angiotensina - (1-7), mas, em camundongos FVB/N." Universidade Federal de Minas Gerais, 2007. http://hdl.handle.net/1843/MCSC-78BU5F.
Full textAbstract:
The metabolic syndrome, also known as insulin resistance syndrome, is characterized by the variable coexistence of obesity, insulin resistance, dislipidemy and hypertension. The angiotensin-(1-7) presents an important contaregulatory role inside Renin Angiotensin System, opposing some times to angiotensina II effects. It has been shown that G protein-coupled receptor, Mas, mediates many actions of angiotensin-(1-7). We have recently observed that Mas-knockout male mice (Mas-/-) in the pure, FVB/N genetic background, presents elevated blood pressure levels and endothelial dysfunction, alterations present in the metabolic syndrome. The aim of this study was to ascertain whether genetic deletion of Mas also changes lipidic and glycemic profile and the mechanisms of these alterations. Ten weeks old Mas-/- and WT mice were used. Curves of plasma glycemia versus time were built after intraperitoneal application of insulin (0.75U/Kg BW) or glucose (2g/Kg BW). After sacrifice, the tissues were weighted and reserved for western blotting and Real-Time PCR. The lipidic profile and the plasma levels of leptin and adiponectin were analyzed using ELISA kits and TGF-â, angiotensinogen and TNF-á mRNA expression was analyzed by Real Time PCR. Despite of having normal body weight (24.7 ± 0.35 vs 24.8± 0.24 g in WT), young Mas-/- mice presented a marked increase in the fat tissue mass (epididimal= 1.704 ± 0.1516 vs 1.150 ± 0.1259 % of BW in WT and retroperitoneal= 0.6747 ± 0.08576 vs 0.3781 ± 0.04575 % of BW in WT). In addition, these animals presented a state of insulin resistance and glucose intolerance as well as an increase in the fasting glycemia levels (86.6 ± 6.43 vs 56.40 ± 4.98 mg/dl in WT). Furthermore, a significant increase in total cholesterol (92.2 ± 3.65 vs 74.6± 5.67 mg/dl in WT) and triglycerides (70.6 ± 13.3 vs 41.4± 4.07 mg/dl in WT) levels were observed. Part of these alterations can be explained by the increase in the leptin plasma levels (1.3 ± 0.25 vs 0.73 ± 0.17 ng/ml in WT) and the decreased Glut4 receptor protein in Mas-/- adipose tissue. The mRNA expression of TGF-â and angiotensinogen was increased in Mas-/- adipose tissue, while the expression of TNF-á, the food intake and adiponectin plasma levels, were not altered. These results show that Mas deficiency in FVB/N mice leads to dramatic changes in glicemic and lipidic metabolism, inducing a metabolic syndrome- like state.A síndrome metabólica, também conhecida como síndrome de resistência à insulina, é caracterizada pela coexistência variável de obesidade, hiperinsulinemia, dislipidemia e hipertensão. A angiotensina-(1-7) apresenta um importante papel contraregulatório dentro do Sistema Renina Angiotensina, se opondo, na maioria das vezes, aos efeitos da angiotensina II. Tem sido demonstrado que o receptor acoplado a proteína G, Mas, medeia várias ações da angiotensina-(1-7). Observamos recentemente que camundongos machos knockout para o receptor Mas (Mas-/-) com background genético FVB/N, apresenta pressão sanguínea elevada e disfunção endotelial, alterações presentes no quadro de síndrome metabólica. O objetivo desse estudo foi verificar se a deleção genética do receptor Mas altera o perfil lipídico e glicêmico desses animais e os mecanismos envolvidos nesse processo. Camundongos WT e knockout machos com aproximadamente dez semanas de vida foram utilizados. Curvas de glicemia pelo tempo foram construídas após aplicação intraperitoneal de insulina (0.75U/Kg) ou glicose (2g/Kg). Após o sacrifício os tecidos foram pesados e reservados para western blotting e Real-Time PCR. O perfil lipídico e os níveis plasmáticos de leptina e adiponectina foram avaliados utilizando kits de ELISA e a expressão do mRNA do TGF-â, angiotensinogênio e do TNF-á foram analisados pela técnica de Real-Time PCR. Apesar de apresentar peso corporal igual ao do controle (24.7 ± 0.35 vs 24.8± 0.24 g no WT), os camundongos Mas-/- jovens apresentaram marcante aumento no peso do tecido adiposo (epididimal= 1.704 ± 0.1516 vs 1.150 ± 0.1259 % do PC no WT e retroperitoneal= 0.6747 ± 0.08576 vs 0.3781 ± 0.04575 % do PC no WT). Além disso, esses animais apresentam resistência a insulina e maior intolerância a glicose, bem como um aumento na glicemia de jejum (86.6 ± 6.43 vs 56.40 ± 4.98 mg/dl no WT). Também foram encontrados aumentos significativos nos níveis plasmáticos de colesterol total (92.2 ± 3.65 vs 74.6± 5.67 mg/dl no WT) e triglicérides (70.6 ± 13.3 vs 41.4± 4.07 mg/dl no WT). Parte dessas alterações podem ser explicadas pelo aumento nos níveis séricos de leptina (1.3 ± 0.25 vs 0.73 ± 0.17 ng/ml no WT) e pela diminuição na expressão protéica do receptor Glut-4 no tecido adiposo epididimal dos Mas-/-. A expressão do RNA mensageiro do TGF-â e do angiotensinogênio estão aumentados no tecido adiposo, enquanto a expressão do TNF-á, o consumo de comida e os níveis plasmáticos de adiponectina, não estão alterados. Juntos, esses dados indicam um importante papel do receptor Mas na função cardiovascular e metabólica em camundongos FVB/N e sugerem um quadro de síndrome metabólica nos camundongos knockout Mas.
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Brito, Rodrigo Guabiraba. "Papel dos receptores canabinóides em um modelo experimental de angiogênese inflamatória." Universidade Federal de Minas Gerais, 2007. http://hdl.handle.net/1843/MCSC-7CDTTF.
Full textAbstract:
Angiogenesis depends on a complex network of cells and mediators. The activation or blockade of cannabinoid receptors showed to be an interesting pharmacological strategy to attenuate the angiogenic and/or inflammatory response in many experimental models. Here we investigated how this strategy may interfere in inflammatory angiogenesis. Polyester-polyurethane sponges were implanted in C57BL/6 mice. Animals received daily doses (10 mg/kg, s.c.) of the cannabinoid antagonists SR141716A (CB1) and SR144528 (CB2), separately, or 3 and 10 mg/Kg (30 or 100 ìg/mice, for the local treatment) (s.c.) of the cannabinoid CB1/CB2 agonist WIN 55212-2, for 7 or 14 days. The implants were then collected for ELISA, hemoglobin, myeloperoxidase and N-acetylglucosaminidase measurements, used as indexes for angiogenesis, neutrophil and macrophage accumulation, respectively. Histological analysis was also conducted. CB1 or CB2 receptor antagonist treatment was able to reduce cellular influx to the sponge at 7 and 14 days, with distinctive pattern for macrophages and neutrophils. The CB1/CB2 agonist also reduced cellular influx. Both treatments affected angiogenesis. These alterations were accompanied by changes in the levels of TNF-á, VEGF, CXCL1-3/KC, CCL2/JE and RANTES, depending on the treatment. All changes correspond to a similar pattern in the histological analysis. The blockade or activation of cannabinoid receptors showed to be effective in reducing inflammatory and angiogenic responses. Altough acting in a similar way, levels of cytokines, chemokines and endocannabinoids may help explain this paradoxal response. Partial agonism / inverse agonism activity and receptor desensitization is another explanation for these responses.
Keywords: angiogenesis, inflammation, cannabinoid receptors, cytokinesA angiogênese é controlada por uma complexa rede de células e mediadores. A ativação ou bloqueio de receptores canabinóides demonstram ser uma interessante estratégia farmacológica para atenuar a resposta angiogênica e/ou inflamatória em vários modelos experimentais. Aqui investigamos como esta estratégia pode interferir na angiogênese inflamatória. Esponjas de polyester-poliuretana foram implantadas em camundongos C57BL/6. Os animais receberam doses diárias (10 mg/Kg, s.c.) dos antagonistas canabinóides SR141716A (CB1) and SR144528 (CB2), separadamente, ou 3 e 10 mg/Kg (30 ou 100 g/animal, para o tratamento local) (s.c.) do agonista CB1/CB2 WIN 55,212-2, por 7 ou 14 dias. Os implantes foram coletados para análises por ELISA, hemoglobina, mieloperoxidase e N-acetilglicosaminidase, utilizadas, respectivamente, como index para mediadores protéicos, angiogênese e acúmulo de neutrófilos e macrófagos, respectivamente. O tratamento com os antagonistas CB1 ou CB2 levou à redução do influxo celular para a matriz esponjosa nos dias 7 e 14, com padrões distintos para macrófagos e neutrófilos. O agonista CB1/CB2 também reduziu o influxo celular. Ambos os tratamentos interferiram na angiogênese. Estas alterações foram acompanhadas por mudanças nos níveis de TNF-, VEGF, CXCL1-3/KC, CCL2/JE e RANTES, dependendo do tratamento. Todas as mudanças apresentam padrões similares na análise histológica. A ativação ou bloqueio de receptores canabinóides parece ser efetivo em reduzir as respostas angiogênica e inflamatória. Embora agindo de forma similar, níveis de citocinas, quimiocinas e endocanabinóides podem explicar esta resposta paradoxal. Desensibilização dos receptores e atividade agonista parcial / agonista inverso são outras explicações plausíveis para estas respostas.
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Carvalho, Luciana Estefani Drumond de. "Participação dos receptores GABAa no potencial excitatório pós sinápitco em hipocampo e amigdala de ratos wistar audiogênicos (WAR)." Universidade Federal de Minas Gerais, 2007. http://hdl.handle.net/1843/MCSC-78PMUL.
Full textAbstract:
Epilepsies are brain disorders characterized by recurrent and
spontaneous crises. They are caused by hyper-synchronized discharges,
localized or generalized through the brain. Their high incidence and prevalence are responsible for both psycho and social impact. An important class of epilepsy is the reflex epilepsy, initiated by exposure to sensory stimulus. The audiogenic crises, a modality of reflex epilepsy, are related to dysfunction of the auditory pathway. The selection of WAR (Wistar Audiogenic Rats) lineage is based on crises susceptibility induced due to the exposure to the high intensity sound stimulus. Nevertheless these animals show greater sensibility to crises when exposed to other convulsive agents such as electroshock, pentyleneterazole and pilocarpina, suggesting changes on their neuronal
network.We study the excitatory post-synaptic potential (EPSP) pattern in the presence and absence of picrotoxin (which blocks the GABAA receptors) in the hippocampus and amygdala of WAR lineage. We also analyze the induction of plastic modifications in the lateral amygdala, in presence or absence of picrotoxin. The results show a reduced response to the toxin, suggesting alteration on the GABAA tonus. In the hippocampus, this points to a generalized dysfunction of the neuronal substrates, but there is no evidence of involvement of such structure in audiogenic crises. Our results also show a tendency to increase in the basal response when compared to the control, suggesting a neuronal circuit more excitable and prone to epileptic crises. We did not observe a low or even standing potentiation in the amygdala, probably caused by its increased and saturated basal response and by a reduced excitatory
modulation. In presence of picrotoxin LTP was not observed for WAR or Wistar group. The inhibitory effect of picrotoxin in EPSP on the amygdala is followed by a recovery response to basal levels, similar to the increase observed for LTP. We conclude that WAR show a GABAA system alteration leading to a hyperexcitability of their neuronal circuits. These animals also behave as resistant Wistar rats when their GABA A system is blocked.As epilepsias são desordens do cérebro manifestadas por crises epilépticas espontâneas e recorrentes. São causadas por descargas neuronais hipersincronizadas, focais ou generalizadas no cérebro. Apresentam altas prevalência e incidência, causam grande impacto psico-social e físico ao seu portador. Uma classe importante de epilepsia é a que engloba as crises reflexas, que são desencadeadas pela exposição do indivíduo suscetível a um estímulo sensorial, em muitos casos bastante específico. A crise audiogênica é uma forma de epilepsia reflexa que está relacionada a disfunção da via auditiva. No entanto, apesar de a seleção da linhagem dos WAR (ratos wistar audiogênicos) ter sido feita pela susceptibilidade dos animais em desencadearem crise quando expostos a um estímulo sonoro de alta intensidade, esses animais apresentam maior sensibilidade, também a desencadearem crises quando expostos a outros agentes convulsivantes como eletrochoque, petilenotetrazol e pilocarpina. Sugerindo a existência de mecanismos que tornam suas redes neurais, de uma forma geral, hiperexcitáveis e hipersincrônicas. Neste trabalho avaliou-se o padrão do Potencial Excitátorio Pós Sináptico (PEPS) na presença e ausência de picrotoxina, bloqueador do sistema GABA A (ã-acído aminobutirico), em dois substratos neurais de WAR: em hipocampo, local onde o GABA exerce efeito inibitório e em amigdala lateral, onde o GABA exerce potente modulação excitatória. Avaliou-se também a capacidade da geração de modificações plásticas na amígdala lateral de WAR, na presença e na ausência de picrotoxina. Observamos baixa responsividade à picrotoxina tanto em hipocampo quanto em amigdala de WAR; sugerindo haver alteração do tônus GABAA nestes dois substratos neurais. A presença desta alteração em hipocampo de WAR, sugere uma disfunção generalizada nos substratos destes animais, uma vez que não há evidências sobre o envolvimento desta estrutura nas crises audiogênicas. Nossos resultados também demonstram uma tendência no aumento das respostas basais nestas duas estruturas dos WAR quando comparadas às dos wistar controles. Sugerindo um circuito neural 2 hiperexcitável e mais propenso à geração de crises epilépticas. Não obtivemos potenciação estável e duradoura em amigdala de WAR, provavelmente devido à sua resposta basal já aumentada e saturada, e devido a uma baixa modulação excitatória neste local. Após adição de picrotoxina não observamos LTP em nenhum dos grupos de animais estudados. Observamos que a ação inibitória da picrotoxina nos PEPS, em amigdala, é seguida por uma recuperação da resposta a níveis basais, aumento semelhante ao ocorrido na potenciação de longo prazo. Os resultados nos permitem concluir que os WAR apresentam alterações no sistema GABAA que favorecem a hiperexitabilidade dos seus circuitos neuronais e que estes animais se comportam como ratos wistar resistentes quando estão com o sistema GABAA bloqueado.
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Ferreira, Monica Alves Neves Diniz. "Avaliação da angiogênese, inflamação e crescimento tumoral em camundongos com deleção gênica dos receptores para o PAF (PAFR-KO)." Universidade Federal de Minas Gerais, 2006. http://hdl.handle.net/1843/MCSC-78AS97.
Full textAbstract:
The endogenous lipid, platelet activating factor (PAF), is usually considered a pro-angiogenic mediator due to its exogenous in vitro
and in vivo effects and to studies with PAF receptor (PAFR) antagonists in vivo. In this study, mice with gene inactivation of the receptor for PAF (PAFR-KO) well used to analyze a range of activities exhibited by this mediator. Two experimental designs were used: the sponge implantation and the growth of solid tumors (Ehrlich and colon) to assess neovascularization, inflammation, cytokine production. Angiogenesis as determined by morphometric analysis and hemoglobin content was significantly higher in the implants and colon tumor of knock out (KO) mice compared with the wild type (WT). VEGF content in the tumors was also, higher in these animals. The levels of TNF-alpha were increased in Ehrlich tumor in KO mice relative to the WT group. Neutrophils and macrophages accumulation, as determined by myeloperoxidase (MPO) and Nacetylglucosaminidase (NAG) were decreased in all proliferating
tissues in KO animals, supporting the pro-inflammatory effects of endogenous PAF. The levels of the pro-inflammatory chemokines did
not follow the same pattern. The growth of colon tumor was not different between the KO and WT mice. However, Ehrlich tumor was six fold bigger in PAFR-KO mice than in WT animals. We have shown that inflammation and angiogenesis in PAFR-KO mice are not necessarily causal events and propose that PAF may be an important endogenous inhibitor of new blood vessels formation and Ehrlich tumor development.O lipídio endógeno, fator ativador plaquetário (PAF), é comumente considerado um mediador pró-inflamatório e pró-angiogênico com base na aplicação exógena deste composto e antagonistas de seus receptores in vitro e in vivo. Neste trabalho, usando camundongos com inativação do gene (nocaute (KO)) para o receptor do PAF (PAFR-KO) foram avaliadas várias atividades deste mediador em dois modelos de angiogênese (modelo de implante de esponjas; angiogênese inflamatória e os tumores sólidos de Ehrlich e cólon; angiogênese tumoral). Nestes modelos foram caracterizadas a neovascularização, a inflamação e a produção de citocinas. Além disso, o crescimento dos tumores sólidos nestes animais foi determinado. A angiogênese, avaliada por análise morfométrica nos implantes e pela dosagem do conteúdo de hemoglobina, nos dois tecidos estava aumentada tanto nos implantes como no tumor de cólon dos animais nocaute. Níveis aumentados do VEGF foram predominantes nos tumores dos animais nocaute (compatível com o aumento da angiogênese) e os do TNF-alfa variaram entre os tecidos avaliados nos dois grupos de animais. O acúmulo de neutrófilos e macrófagos determinados pela atividade das enzimas mieloperoxidade (MPO) e N-acetilglucosaminidase (NAG) respectivamente, nos implantes e tecidos tumorais foram significativamente menores nos animais PAFR-KO, confirmando os efeitos pró-inflamatórios do PAF. Os níveis da quimiocina KC foram maiores no implante dos animais nocaute. Nos tumores, esta quimiocina foi menor apenas no tumor de Ehrlich nestes animais. Não houve diferença entre os pesos dos tumores de cólon nos dois grupos de animais. No entanto, o crescimento do adenocarcinoma de Ehrlich no período de 25 dias foi seis vezes maior nos animais KO comparados aos selvagens. Os resultados deste estudo mostram que a inflamação e a angiogênese em camundongos PAFR-KO não são eventos causais e propomos que o PAF endógeno pode ser um importante mediador inibitório da neo-formação vascular e do desenvolvimento do tumor sólido de Ehrlich.
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Srinivasan, Sathish. "Role of E6-AP in Steroid Hormone Receptor-Dependent Transcription and Cellular Function." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/345.
Full textAbstract:
Steroid receptor coactivators modulate the final outcome of hormone induced gene transcription by steroid receptors. E6-associated protein (E6-AP), an E3 ubiquitin ligase, acts as a coactivator of steroid receptors, including estrogen receptor (ER). In this study, we elucidated the contribution of E6-AP to ER-dependent gene transcription in breast cancer cells. siRNA-mediated knockdown of E6-AP abrogates transcription of classic ER target genes, GREB1 and pS2, suggesting that E6-AP is essential for normal transactivation function of ER. In order to understand the global influence of E6-AP in ER-dependent gene transcription, we used gene expression microarrays under E6-AP knockdown conditions to identify ER target genes which are regulated by E6-AP. Our microarray analysis revealed 455 genes which are differentially regulated by E6-AP. Pathway analysis revealed that E6-AP regulated genes were involved in cell cycle. Cell cycle profiling at various time points of estrogen treatment reveals that under E6-AP knockdown conditions, breast cancer cells progress slowly through S phase and eventually fail to proliferate. Knockdown of E6-AP has no effect on ovarian and uterine cells, suggesting that E6-AP has cell specific roles. Our analysis suggests that knockdown of E6-AP reduces the levels of early (C-Myc and Cyclin-D1), mid (E2F1, E2F2 and E2F7) and late (BUB1, BUBR1, MAD2, NDC80, NUF2 and CASC5) estrogen-dependent cell cycle genes. Overall our data indicate that E6-AP is a major regulator of cell cycle in breast cancer cells. E6-AP also acts as a coactivator for androgen receptor (AR) and we studied the role of E6-AP in prostate gland development. We report the generation of transgenic mice which specifically over expresses E6-AP in the prostate gland. Prostate glands in these mice are larger when compared with its wild-type litter mates, corroborating our observations that knockout of E6-AP in mice leads to impaired prostate gland development. E6-AP transgenic mice also develop prostatic intra epithelial neoplasia after 18 months of age. In addition to these observations, we also show that over expression of E6-AP in the prostate gland leads to increased Akt signaling. In order to understand the mechanism by which E6-AP regulates prostate gland growth, we generated LNCaP cells that stably overexpress E6-AP protein. Data from these cell lines show that the levels of phosphatidylinositol 3-kinase, total Akt, phosphorylated Akt (active Akt) and its down-stream target protein, GSKβ are elevated, suggesting that E6-AP regulates the PI3K-Akt signaling pathway. We further show that E6-AP modulates PI3K-Akt signaling by regulating the protein levels of RhoA, a small GTPase, which is a negative regulator of the Akt signaling pathway. In addition, we show that stable overexpression of E6-AP in prostate cancer cells results in increased proliferation. Overall our data suggests that E6-AP regulates the PI3K-Akt pathway in prostate cells which results in increased prostate cell growth, proliferation and tumorigenesis.
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Santos, Adriana Carvalho dos. "Estudo in vivo do papel das quimiocinas e dos receptores de bradicinina, B1 e B2, no recrutamento de leucócitos na microvasculatura cerebral de camundongos com Encefalomielite Autoimune Experimental." Universidade Federal de Minas Gerais, 2006. http://hdl.handle.net/1843/MCSC-7CHT92.
Full textAbstract:
Experimental autoimmune encephalomyelitis (EAE) models multiple sclerosis (MS) and is characterized by marked mononuclear cell influx in the brain.
Inflammation leads to demyelinating lesions and disease. Several studies have demonstrated a role for chemokines during EAE. It remains to be determined whether these mediators modulate EAE primarily by mediating leukocyte influx into the CNS or by modifying lymphocyte activation and/or trafficking into lymphoid organs. After induction of EAE with MOG35-55, leukocyte recruitment peaked on day 14 and correlated with symptom onset, TNF-á production and production of CCL2
and CCL5. Levels of CXCL-10 and CCL3 were not different from control animals.
We demonstrated that leukocyte rolling and adhesion also peaked at day 14. The treatment with anti-CCL2 or anti-CCL5 antibodies just prior to the intravital microscopy prevented leukocyte adhesion, but not rolling. To confirm the role of CCL2 on leukocyte recruitment, we performed different treatments with the mutant protein P8A, described as an inhibitor of CCL2 activity. P8A was able to decrease leukocyte adhesion and ameliorated the clinical course of disease. Our data suggest that induction of leukocyte adhesion to the brain microvasculature is an important mechanism by which CCL2 and CCL5 participate in the pathogenesis of
EAE. Next, we investigated the role of kinins in driving EAE and chemokine production in the brain. The kinins are relevant mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. For the present study B1- deficient (B1-/-), B2-deficient (B2- /-) and wild type (WT) mice were used. The incidence of disease was similar in the groups, but the disease in B2-/- mice was less severe. At day 14 after EAE induction, there was a significant decrease in the
number of adherent leukocytes when compared with WT mice. EAE induced an increase of B1 mRNA in brain tissue and this was partially prevented in B2-/- mice. Expression of CCL5 was suppressed in both B1
-/- and B2 -/- mice, but CCL2 expression was only inhibited in B2-/- mice. Altogether, our results suggest that B2 receptors have two major effects in the control of EAE severity: B2 regulates the expression of chemokines, including CCL2 and CCL5, the expression of B1 receptors, and B1-dependent leukocyte influx. Blockade of chemokine action (eg.
by using P8A) or production (eg. by using bradykinin antagonists) may represent a valid strategy to prevent leukocyte influx into the brain and disease severity in patients with MS.A Encefalomielite Autoimune Experimental (EAE), modelo animal da Esclerose Multipla (EM), e caracterizada como uma doenca inflamatoria cronica, com um intenso influxo de celulas mononucleares para o sistema nervoso central (SNC). Varios estudos tem demonstrado uma participacao das quimiocinas durante a EAE, mas ainda nao foi esclarecido como esses mediadores regulam o recrutamento de leucocitos para o SNC. Apos a inducao da EAE com MOG35-55, o recrutamento de leucocitos foi marcante no dia 14 apos a inducao, com um aumento dos eventos de rolamento e adesao, correlacionando com o pico de manifestacao clinica e inflamacao, assim como um aumento da producao de TNF¿, CCL2 e CCL5. Nenhuma diferenca foi observada quanto aos niveis de CCL3 e CXCL10. O tratamento com anticorpos anti-CCL2 e anti-CCL5 2h antes da microscopia intravital foi capaz de promover uma diminuicao no processo de adesao, sem alterar o rolamento. Para confirmar o papel da quimiocina CCL2 no recrutamento de leucocitos, foram realizados diferentes tratamentos com a proteina mutante P8A, descrita como inibidora da atividade da CCL2. A proteina P8A foi capaz de diminuir a adesao de leucocitos e exibir um quadro clinico menos grave. Esses dados sugerem que a inducao da adesao de leucocitos na microvasculatura cerebral e um evento importante na patogenia da EAE e que as quimiocinas CCL2 e CCL5 podem modular este processo. Depois foi investigado o papel das cininas no recrutamento de leucocitos para o SNC no mesmo modelo. As cininas sao mediadores relevantes da inflamacao e atuam atraves de dois receptores especificos acoplados a proteina G, B1 e B2. Para este estudo foram utilizados animais WT, B1-/- e B2-/-. A incidencia da doenca foi similar entre os grupos, mas os animais B2 -/- exibiram menor gravidade da doenca. No dia 14o apos a inducao, houve uma diminuicao do numero de leucocitos aderidos nos animais knockout quando comparados com animais WT. Alem disso, animais com EAE demonstraram um aumento da expressao de receptores B1 no extrato de cerebro, parcialmente diminuidos nos animais B2 -/-. A producao de CCL5 foi diminuida nos animais B1 -/- e B2 -/-, mas CCL2 apenas foi diminuida nos animais B2 -/-. Contudo, esses resultados sugerem que receptores B2 possuem um importante papel no controle da doenca, via regulacao da expressao de B1, modulacao da quimiocina CCL2 e, consequente, controle da adesao de leucocitos. Logo, o bloqueio da atividade da quimiocina CCL2 pelo uso da P8A ou por antagonistas de BK pode representar uma importante estrategia para suprimir o influxo de leucocitos para o SNC e, consequentemente, controlar a gravidade da doenca.
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Silva, Danielle. "Estudo da ação dicotômica do receptor de estrógeno beta (ERβ) na indução da transição epitélio- mesênquima em células tumorais de mama da linhagem MCF-7." Universidade Federal de Uberlândia, 2017. http://dx.doi.org/10.14393/ufu.di.2018.56.
Full textAbstract:
CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorO câncer de mama é a neoplasia que mais acomete mulheres no mundo. Dentre os fatores prognósticos levados em consideração estão os receptores hormonais. O receptor de estrógeno beta (ERβ) é um dos receptores hormonais que pode ser encontrado na mama, mas que até então não é utilizado como um marcador preditivo de prognóstico tumoral por conta da sua ação paradoxal. Células tumorais de mama da linhagem MCF-7 foram utilizadas neste trabalho para averiguar a função dicotômica do ERβ no processo tumoral. De tal forma que foi avaliado alguns dos processos que são observados nas etapas do desenvolvimento do câncer de mama, como proliferação, transição epitélio-mesênquima (EMT) e investigação das células -tronco cancerosas (CSCs) . Para isso, foram utilizados o agonista de ERβ, Diarilpropionitrilo (DPN), o agonista ambíguo (ERα e ERβ) estradiol (E2) e o fator de crescimento transformante beta (TGF-β), indutor de EMT. As células que receberam tratamento com DPN obtiveram maior número de CSCs comparadas às que não foram cultivadas com esse agonista, resultado encontrado pela técnica de citometria de fluxo. As células que tiveram um tratamento prévio com TGF-β demonstraram menor taxa de proliferação e aumento na expressão de p21, uma proteína com ação bloqueadora de ciclina D1, cuja expressão ficou inalterada nos tratamentos com TGF-β e agonista de ERβ. A respeito dos genes relacionados a EMT (SLUG, SNAIL,VIMENTINA, ZEB1,TWIST1,RBFOX2,CICLINAD1 e p21), ERβ inibiu a expressão dos mesmos, sugerindo que esse receptor induza o fenômeno denominado transição mesenquimal epitelial (MET). Nesse cenário, DPN causou a diminuição da expressão de SLUG, SNAIL, TWIST, contrastando com a expressão obtida no tratamento com TGF-β que, além desses genes, também demonstrou aumento na expressão de ZEB1, RBFOX2 e vimentina. O efeito do TGF-β na EMT foi revertido ao associá-lo com DPN. Os dados corroboram com a literatura acerca do possível papel pró tumoral de ERβ no aumento da proliferação celular e da geração das células-tronco cancerígenas de mama (BSCs), além de ir ao encontro do fenótipo relacionado a MET nos tratamentos com DPN sozinho ou associado ao TGF-β. Com esses resultados, torna-se claro no nosso trabalho que dependendo o que é avaliado em relação a ação do ERβ, previamente tratado ou não com TGF-β, o seu efeito dicotômico ainda é observado.
Breast cancer is the most common neoplasm of women in the world. Among the prognostic factors taken into consideration are the hormonal receptors. The estrogen receptor beta (ERβ) is one of the hormone receptors that can be found in the breast, but is not used as a predictive marker of tumor prognosis due to its paradoxical action. Tumor cells of the MCF-7 lineage were used in this work to ascertain the dichotomic function of ERβ in the tumor process. Thus, we evaluated some of the processes that are observed in the stages of breast cancer development, such as proliferation, epithelial-mesenchymal transition (EMT) and cancer stem cell research (CSCs). For this, ERβ agonist Diarilpropionitrile (DPN), ambiguous agonist (ERα and ERβ) estradiol (E2) and transforming growth factor beta (TGF-β), inducer of EMT, were used. Cells receiving TGF- β treatment obtained a higher number of CSCs compared to those that were not cultured with this agonist, a result found by the flow cytometry technique. Cells that were pretreated with TGF-β demonstrated a lower rate of proliferation and increased expression of p21, a protein with cyclin D1 blocking action, whose expression was unchanged in TGF-β and ERβ agonist treatments. Regarding the EMT-related genes (SLUG, SNAIL, VIMENTINA, ZEB1, TWIST1, RBFOX2, CYCLINAD1 and p21), ERβ inhibited their expression, suggesting that this receptor induces the phenomenon called epithelial mesenchymal transition (MET). In this scenario, DPN caused a decrease in the expression of SLUG, SNAIL, TWIST, in contrast to TGF-β expression, which, in addition to these genes, also showed increased expression of ZEB1, RBFOX2 and VIMENTIN. The effect of TGF-β on EMT was reversed by associating it with DPN. The data corroborate with the literature about the possible ERβ pro-tumor role in increasing cell proliferation and the generation of breast cancer stem cells (BSCs), in addition to the MET related phenotype in treatments with DPN alone or associated to TGF-β. With these results, it becomes clear in our work that depending on what is evaluated in relation to the action of ERβ, previously treated or not with TGF-β, its dichotomous effect is still observed.
Dissertação (Mestrado)
Books on the topic "MCSF receptor"
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Lenk, John D. Complete guide to stereo television (MTS/MCS) troubleshooting and repair. Englewood Cliffs, N.J: Prentice-Hall, 1988.
Find full textBook chapters on the topic "MCSF receptor"
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Ruh, T. S., M. F. Ruh, and R. K. Singh. "Antiestrogen Action in MCF-7 Cells." In Receptor Mediated Antisteroid Action, edited by M. K. Agarwal, 307–28. Berlin, Boston: De Gruyter, 1987. http://dx.doi.org/10.1515/9783110846935-013.
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Prévost, Grégoire, Nathalie Veber, Lucien Israël, and Philippe Planchon. "Growth Hormone Releasing Hormone Receptor in Human Breast Cancer Cell Line MCF-7." In Growth Hormone Secretagogues, 127–34. New York, NY: Springer New York, 1996. http://dx.doi.org/10.1007/978-1-4612-2396-2_9.
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VILLACAMPA, M. J., R. MORO, J. NAVAL, C. FAILLY-CRÉPIN, J. URIEL, F. LAMPREAVE, and M. GEUSKENS. "Evidence for Alpha-Fetoprotein Receptors in the MCF-7 Human Breast Cancer Cell Line." In Protides of the Biological Fluids, 575–78. Elsevier, 1985. http://dx.doi.org/10.1016/b978-0-08-031739-7.50144-0.
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Schmidt-Ullrich, R., K. Valerie, Chan WM, Lin P-S, and Wazer DE. "EXPRESSION OF ESTROGEN RECEPTOR AND TRANSFORMING GROWTH FACTORS IN MCF-7 CELLS EXPOSED TO FRACTIONATED IRRADIATION." In Radiation Research: A Twentieth-century Perspective, 222. Elsevier, 1991. http://dx.doi.org/10.1016/b978-0-12-168561-4.50792-7.
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Giordano, C., D. Vizza, S. Panza, I. Barone, D. Bonofiglio, S. Fuqua, S. Catalano, and S. Ando. "Activated Farnesoid X Receptor Inhibits Growth of Tamoxifen-Resistant MCF-7 Breast Cancer Cells, through Down-Regulation of HER2 Expression." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P3–58—P3–58. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part3.p2.p3-58.
Full textConference papers on the topic "MCSF receptor"
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Chan, Bonita Tak-Yee, Isere Kuiatse, and Adrian V. Lee. "Abstract 5056: Signaling pathways critical for insulin receptor substrate (IRS)-mediated disruption of MCF-10A acini formation." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5056.
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Zhang, X., MR Diaz, and D. Yee. "P4-01-14: Fulvestrant Regulates Epidermal Growth Factor (EGF) Ligands and Induces EGF Receptor Activation in MCF-7 Breast Cancer Cells." In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-p4-01-14.
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Ekyalongo, RC, T. Mukohara, Y. Kataoka, N. Kiyota, Y. Fujiwara, and H. Minami. "P5-06-04: Mechanisms of Acquired Resistance to Insulin-Like Growth Factor 1 Receptor Inhibitor in MCF-7 Breast Cancer Cell Line." In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-p5-06-04.
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Shestakova, E., A. Scherbakov, O. Ryabinina, A. Grishanina, K. Galeeva, and T. Bogush. "PO-147 Hypoxia, estrogens and phytoestrogens influence BRCA1 and oestrogen receptors α expression in MCF-7 breast cancer cell line." In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.669.
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Datta, Amrita, Barbara J. Rider, Asim B. Abdel-Mageed, and Krishna C. Agrawal. "Abstract 5419: Effects of selective aryl hydrocarbon receptor modulators (SAhRMs) in enhancing activity of tamoxifen against doxorubicin resistant MCF-7 Cells: Role of BRCA1." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5419.
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Brantley, Eileen, Nicole Mavingire, Jonathan Wooten, and Petreena Campbell. "Abstract 1304: Aryl hydrocarbon receptor ligands 5F 203 and 3,3'-Diindolylmethane disrupt mammospheres derived from MCF-7 cells and induce tumor suppressor miR125b-2 expression." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-1304.
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Telang, NT, G. Li, DW Sepkovic, LH Bradlow, GGY Wong, and NT Telang. "P3-09-04: Comparative Preventive Efficacy of Aqueous Extracts from Lycium Barbarum Bark and Fruit on Estrogen Receptor Positive Human Mammary Carcinoma MCF-7 Cells." In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-p3-09-04.
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Brantley, Eileen, Nicole Mavingire, Jonathan Wooten, and Petreena Campbell. "Abstract 1304: Aryl hydrocarbon receptor ligands 5F 203 and 3,3'-Diindolylmethane disrupt mammospheres derived from MCF-7 cells and induce tumor suppressor miR125b-2 expression." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-1304.
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Zhang, Xihong, Sidhant Varma, and Douglas Yee. "Abstract P6-12-05: Inducible suppression of insulin receptor substrate I inhibits IGF-I/insulin/estradiol dependent cell growth in MCF-7L breast cancer cells." In Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.sabcs14-p6-12-05.
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Zhang, Xihong, Sidhant Varma, and Douglas Yee. "Abstract 4406: Inducible knockdown of insulin receptor substrate I desensitizes ER alpha response to both agonist (estradiol) and antagonist (fulvestrant) in MCF-7L breast cancer cells." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4406.
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