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Journal articles on the topic 'D1-class receptor'

Author: Grafiati

Published: 4 June 2021

Last updated: 8 February 2022

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1

Watanabe, Katsushige, and Minoru Kimura. "Dopamine Receptor–Mediated Mechanisms Involved in the Expression of Learned Activity of Primate Striatal Neurons." Journal of Neurophysiology 79, no. 5 (1998): 2568–80. http://dx.doi.org/10.1152/jn.1998.79.5.2568.

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Watanabe, Katsushige and Minoru Kimura. Dopamine receptor–mediated mechanisms involved in the expression of learned activity of primate striatal neurons. J. Neurophysiol. 79: 2568–2580, 1998. To understand the mechanisms by which basal ganglia neurons express acquired activities during and after behavioral learning, selective dopamine (DA) receptor antagonists were applied while recording the activity of striatal neurons in monkeys performing behavioral tasks. In experiment 1, a monkey was trained to associate a click sound with a drop of reward water. DA receptor antagonists were administered

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Ibañez-Sandoval, Osvaldo, Adán Hernández, Benjamin Florán, et al. "Control of the Subthalamic Innervation of Substantia Nigra Pars Reticulata by D1 and D2 Dopamine Receptors." Journal of Neurophysiology 95, no. 3 (2006): 1800–1811. http://dx.doi.org/10.1152/jn.01074.2005.

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The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and d-(−)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of ( RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-

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Wang, Chenguang, Nagarajan Pattabiraman, Jian Nian Zhou та ін. "Cyclin D1 Repression of Peroxisome Proliferator-Activated Receptor γ Expression and Transactivation". Molecular and Cellular Biology 23, № 17 (2003): 6159–73. http://dx.doi.org/10.1128/mcb.23.17.6159-6173.2003.

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ABSTRACT The cyclin D1 gene is overexpressed in human breast cancers and is required for oncogene-induced tumorigenesis. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor selectively activated by ligands of the thiazolidinedione class. PPARγ induces hepatic steatosis, and liganded PPARγ promotes adipocyte differentiation. Herein, cyclin D1 inhibited ligand-induced PPARγ function, transactivation, expression, and promoter activity. PPARγ transactivation induced by the ligand BRL49653 was inhibited by cyclin D1 through a pRB- and cdk-independent mechanism, requiring a re

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Yamamoto, Kei, Olivier Mirabeau, Charlotte Bureau, et al. "Evolution of Dopamine Receptor Genes of the D1 Class in Vertebrates." Molecular Biology and Evolution 30, no. 4 (2012): 833–43. http://dx.doi.org/10.1093/molbev/mss268.

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Sasikumar, T. K., D. A. Burnett, H. Zhang, A. Smith-Torhan, A. Fawzi, and J. E. Lachowicz. "Hydrazides of clozapine: A new class of D1 dopamine receptor subtype selective antagonists." Bioorganic & Medicinal Chemistry Letters 16, no. 17 (2006): 4543–47. http://dx.doi.org/10.1016/j.bmcl.2006.06.022.

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Vargo, J. M., B. B. Bromberg, P. J. Best, J. V. Corwin, and J. F. Marshall. "D1-class dopamine receptor involvement in the behavioral recovery from prefrontal cortical injury." Behavioural Brain Research 72, no. 1-2 (1995): 39–48. http://dx.doi.org/10.1016/0166-4328(95)00028-3.

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Shayegan, Darius K., and Stephen M. Stahl. "Atypical Antipsychotics: Matching Receptor Profile to Individual Patient's Clinical Profile." CNS Spectrums 9, S11 (2004): 6–14. http://dx.doi.org/10.1017/s1092852900025086.

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AbstractUnderstanding common pharmacologic and clinical “class” actions associated with atypical antipsychotics certainly reveals how these agents are alike, but what about unique differences from one agent to another? Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1 (D3, and D4) and multiple serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical antipsychotics also interact with noradrenergic (α1- and α2-adrenergic receptor blockade), histaminergic (H1-receptor b

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Sakurai, Atsuko, Julie Gavard, Yuliya Annas-Linhares, et al. "Semaphorin 3E Initiates Antiangiogenic Signaling through Plexin D1 by Regulating Arf6 and R-Ras." Molecular and Cellular Biology 30, no. 12 (2010): 3086–98. http://dx.doi.org/10.1128/mcb.01652-09.

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ABSTRACT Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here that Sema3E acts as a potent inhibitor of adult and tumor-induced angiogenesis. Activation of plexin D1 by Sema3E causes the rapid disassembly of integrin-mediated adhesive structures, thereby inhibiting endothelial cell adhesion to the extracellular

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Prommer, Eric. "Olanzapine." American Journal of Hospice and Palliative Medicine® 30, no. 1 (2012): 75–82. http://dx.doi.org/10.1177/1049909112441241.

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Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D1, D2, D3, and D4), serotonergic (5-hydroxytryptamine 2A [5-HT2A], 5-HT2C, 5-HT3, and 5-HT6), adrenergic (α1), histaminic (H1), and muscarinic (M1, M2, M3, and M4) receptors. Olanzapine has a high affinity for the 5HT2A receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the iden

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Martini, Michael L., Jing Liu, Caroline Ray, et al. "Defining Structure–Functional Selectivity Relationships (SFSR) for a Class of Non-Catechol Dopamine D1 Receptor Agonists." Journal of Medicinal Chemistry 62, no. 7 (2019): 3753–72. http://dx.doi.org/10.1021/acs.jmedchem.9b00351.

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11

Tseng, K. Y., L. A. Riquelme, and M. G. Murer. "Impact of d1-class dopamine receptor on striatal processing of cortical input in experimental parkinsonism in vivo." Neuroscience 123, no. 2 (2004): 293–98. http://dx.doi.org/10.1016/j.neuroscience.2003.10.005.

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Iype, Elizabeth Mathew, Rajan Balakrishna, Lakshmi Subhadradevi, Jissa Vinoda Thulaseedharan, Bharath Veerabadhran, and Jayasree Kattoran. "Expression of proliferation markers in laryngeal squamous cell carcinoma: an association with clinico-pathological factors and treatment outcomes." International Journal of Otorhinolaryngology and Head and Neck Surgery 6, no. 5 (2020): 858. http://dx.doi.org/10.18203/issn.2454-5929.ijohns20201675.

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<p class="abstract"><strong>Background:</strong> The study was done with the objective to study the expression of epidermal growth factor receptor (EGFR), cyclin D1 and Ki-67 in laryngeal squamous cell carcinoma and to assess the correlation of all three proliferation markers with various clinic-pathological parameters, the treatment outcomes as well as survival.</p><p class="abstract"><strong>Methods:</strong> We prospectively evaluated the surgical specimens of 72 laryngeal squamous cell carcinoma (LSCC) patients, treated with primary surgery and pos

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Błaszczak-Świątkiewicz, Katarzyna. "New Selective Progesterone Receptor Modulators and Their Impact on the RANK/RANKL Complex Activity." Molecules 25, no. 6 (2020): 1321. http://dx.doi.org/10.3390/molecules25061321.

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Breast cancer depends on women’s age. Its chemotherapy and hormone therapy lead to the loss of bone density and disruption of the skeleton. The proteins RANK and RANKL play a pivotal role in the formation of osteoclasts. It is also well established that the same proteins (RANK and RANKL) are the main molecules that play an important role in mammary stem cell biology. Mammary stem cells guarantee differentiation of the epithelial mammary cells, the growth of which is regulated by the progesterone-induced RANKL signaling pathway. The crosstalk between progesterone receptor, stimulated by progest

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Ali, Mohamed, Sara Mahmoud Shahin, Nagwa Ali Sabri, Ayman Al-Hendy та Qiwei Yang. "Activation of β-Catenin Signaling and its Crosstalk With Estrogen and Histone Deacetylases in Human Uterine Fibroids". Journal of Clinical Endocrinology & Metabolism 105, № 4 (2019): e1517-e1535. http://dx.doi.org/10.1210/clinem/dgz227.

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Abstract Context Uterine fibroids (UF) are the most common benign tumor of the myometrium (MM) in women of reproductive age. However, the mechanism underlying the pathogenesis of UF is largely unknown. Objective To explore the link between nuclear β-catenin and UF phenotype and β-catenin crosstalk with estrogen and histone deacetylases (HDACs). Design Protein/RNA levels of β-catenin (CTNNB1 gene), its responsive markers cyclin D1 and c-Myc, androgen receptor (AR), p27, and class-I HDACs were measured in matched UF/MM tissues or cell populations. The effects of chemical inhibition/activation an

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Amenta, Francesco, Livio Chiandussi, Maurizio Mancini, Alberto Ricci, Marina Schena, and Franco Veglio. "Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex." European Journal of Endocrinology 131, no. 1 (1994): 91–96. http://dx.doi.org/10.1530/eje.0.1310091.

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Amenta F, Chiandussi L, Mancini M, Ricci A, Schena M, Veglio F. Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex. Eur J Endocrinol 1994;131:91–6. ISSN 0804–4643 The pharmacological characteristics and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of the human adrenal cortex using radioligand binding and autoradiographic techniques. [3H]SCH23390 was used as a ligand of D1-like receptors, whereas [3H]spiroperidol was used to label D2-like receptors. No specific [3H]SCH 23390 bindi

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Fyfe, Tim J., Peter J. Scammells, J. Robert Lane, and Ben Capuano. "Enantioenriched Positive Allosteric Modulators Display Distinct Pharmacology at the Dopamine D1 Receptor." Molecules 26, no. 13 (2021): 3799. http://dx.doi.org/10.3390/molecules26133799.

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(1) Background: Two first-in-class racemic dopamine D1 receptor (D1R) positive allosteric modulator (PAM) chemotypes (1 and 2) were identified from a high-throughput screen. In particular, due to its selectivity for the D1R and reported lack of intrinsic activity, compound 2 shows promise as a starting point toward the development of small molecule allosteric modulators to ameliorate the cognitive deficits associated with some neuropsychiatric disease states; (2) Methods: Herein, we describe the enantioenrichment of optical isomers of 2 using chiral auxiliaries derived from (R)- and (S)-3-hydr

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Boyle, Kathleen A., and Teresa Compton. "Receptor-Binding Properties of a Soluble Form of Human Cytomegalovirus Glycoprotein B." Journal of Virology 72, no. 3 (1998): 1826–33. http://dx.doi.org/10.1128/jvi.72.3.1826-1833.1998.

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ABSTRACT The human cytomegalovirus (HCMV) glycoprotein B (gB) (also known as gpUL55) homolog is an important mediator of virus entry and cell-to-cell dissemination of infection. To examine the potential ligand-binding properties of gB, a soluble form of gB (gB-S) was radiolabeled, purified, and tested in cell-binding experiments. Binding of gB-S to human fibroblast cells was found to occur in a dose-dependent, saturable, and specific manner. Scatchard analysis demonstrated a biphasic plot with the following estimated dissociation constants (Kd ): K d1, 4.96 × 10−6 M; K d2, 3.07 × 10−7 M. Cell

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Opazo, Juan C., Kattina Zavala, Soledad Miranda-Rottmann, and Roberto Araya. "Evolution of dopamine receptors: phylogenetic evidence suggests a later origin of the DRD2l and DRD4rs dopamine receptor gene lineages." PeerJ 6 (April 13, 2018): e4593. http://dx.doi.org/10.7717/peerj.4593.

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Dopamine receptors are integral membrane proteins whose endogenous ligand is dopamine. They play a fundamental role in the central nervous system and dysfunction of dopaminergic neurotransmission is responsible for the generation of a variety of neuropsychiatric disorders. From an evolutionary standpoint, phylogenetic relationships among the DRD1 class of dopamine receptors are still a matter of debate as in the literature different tree topologies have been proposed. In contrast, phylogenetic relationships among the DRD2 group of receptors are well understood. Understanding the time of origin

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Singh-Jasuja, Harpreet, René E. M. Toes, Pieter Spee, et al. "Cross-Presentation of Glycoprotein 96–Associated Antigens on Major Histocompatibility Complex Class I Molecules Requires Receptor-Mediated Endocytosis." Journal of Experimental Medicine 191, no. 11 (1999): 1965–74. http://dx.doi.org/10.1084/jem.191.11.1965.

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Heat shock proteins (HSPs) like glycoprotein (gp)96 (glucose-regulated protein 94 [grp94]) are able to induce specific cytotoxic T lymphocyte (CTL) responses against cells from which they originate. Here, we demonstrate that for CTL activation by gp96-chaperoned peptides, specific receptor-mediated uptake of gp96 by antigen-presenting cells (APCs) is required. Moreover, we show that in both humans and mice, only professional APCs like dendritic cells (DCs), macrophages, and B cells, but not T cells, are able to bind gp96. The binding is saturable and can be inhibited using unlabeled gp96 molec

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Omeljaniuk, Robert J. "Specific [3H]spiperone binding sites in the pituitary of rainbow trout (Oncorhynchus mykiss) and goldfish (Carassius auratus)." Canadian Journal of Physiology and Pharmacology 73, no. 5 (1995): 585–93. http://dx.doi.org/10.1139/y95-074.

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Dopamine, a catecholamine neurohormone, modulates pituitary hormone release in teleost fishes and other vertebrates. The existence and binding parameters of a pituitary dopamine–neuroleptic receptor from trout were examined and compared with those from goldfish. Pituitary homogenate was incubated with [3H]spiperone (D2 antagonist) under several experimental paradigms; incubations were terminated by filtration and bound 3H radioactivity was assessed by liquid scintillation spectroscopy. Specific binding of [3H]spiperone was tissue dependent. Equilibrium displacement analyses using domperidone (

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Sinnett-Smith, James, Yang Ni, Jia Wang, Ming Ming, Steven H. Young, and Enrique Rozengurt. "Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling." American Journal of Physiology-Cell Physiology 306, no. 10 (2014): C961—C971. http://dx.doi.org/10.1152/ajpcell.00048.2014.

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We examined whether class IIa histone deacetylases (HDACs) play a role in mitogenic signaling mediated by protein kinase D1 (PKD1) in IEC-18 intestinal epithelial cells. Our results show that class IIa HDAC4, HDAC5, and HDAC7 are prominently expressed in these cells. Stimulation with ANG II, a potent mitogen for IEC-18 cells, induced a striking increase in phosphorylation of HDAC4 at Ser246 and Ser632, HDAC5 at Ser259 and Ser498, and HDAC7 at Ser155. Treatment with the PKD family inhibitors kb NB 142-70 and CRT0066101 or small interfering RNA-mediated knockdown of PKD1 prevented ANG II-induced

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Avila, DM, SA Fuqua, FW George, and MJ McPhaul. "Identification of genes expressed in the rat prostate that are modulated differently by castration and Finasteride treatment." Journal of Endocrinology 159, no. 3 (1998): 403–11. http://dx.doi.org/10.1677/joe.0.1590403.

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In mammals, testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens). Testosterone is the most abundant circulating androgen, and is converted in specific tissues to DHT by the 5alpha-reductase enzymes. Although each of these androgens binds to the same receptor protein (androgen receptor, AR), each exerts biologically distinct effects. Theories to explain the specific effects of testosterone and DHT have centered on kinetic differences of binding of androgens to the receptor or differences in the metabolic fates of the two hormones. In the current experime

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Seiler, Max P., Alexander Hagenbach, Hans Juerg Wuethrich, and Rudolf Markstein. "trans-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines"), the first structural class of potent and selective dopamine D1 receptor agonists lacking a catechol group." Journal of Medicinal Chemistry 34, no. 1 (1991): 303–7. http://dx.doi.org/10.1021/jm00105a047.

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Tang, Jinhua, Yanli Yan, Ting C. Zhao, George Bayliss, Haidong Yan, and Shougang Zhuang. "Class I histone deacetylase activity is required for proliferation of renal epithelial cells." American Journal of Physiology-Renal Physiology 305, no. 3 (2013): F244—F254. http://dx.doi.org/10.1152/ajprenal.00126.2013.

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The process of renal regeneration after acute kidney injury is thought to recapitulate renal development, and proliferation of renal proximal tubular cells (RPTCs) is a critical step in the regenerative response. Recent studies indicate that class I histone deacetylases (HDACs) are required for embryonic kidney gene expression, growth, and differentiation. The role and underlying mechanisms of class I HDAC activation in RPTC proliferation, however, remain unclear. In this study, we used cultured RPTCs to examine this issue since four class I HDAC isoforms (1, 2, 3, and 8) are abundantly expres

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Orr, Sarah K., Romain A. Colas, Jesmond Dalli, Nan Chiang, and Charles N. Serhan. "Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent." American Journal of Physiology-Lung Cellular and Molecular Physiology 308, no. 9 (2015): L904—L911. http://dx.doi.org/10.1152/ajplung.00370.2014.

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Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17 R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA

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SEILER, M. P., A. HAGENBACH, H. J. WUETHRICH, and R. MARKSTEIN. "ChemInform Abstract: trans-Hexahydroindolo(4,3-ab)phenanthridines (“Benzergolines”), the First Structural Class of Potent and Selective Dopamine D1 Receptor Agonists Lacking a Catechol Group." ChemInform 22, no. 24 (2010): no. http://dx.doi.org/10.1002/chin.199124230.

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Mitrofanova, L. B., A. A. Perminova, N. S. Goncharova, and E. N. Mikhailov. "Histological and immunohistochemical study of nerve fibers and ganglia in the periarterial adipose tissue of the pulmonary artery bifurcation in patients with and without pulmonary hypertension." "Arterial’naya Gipertenziya" ("Arterial Hypertension") 25, no. 5 (2020): 498–509. http://dx.doi.org/10.18705/1607-419x-2019-25-5-498-509.

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Background. One of the possible methods of reducing pressure in the pulmonary artery (PA) in pulmonary hypertension (PH) is radiofrequency damage of the periarterial nerve fibers. At the same time, the impact of the autonomic nervous system has not been fully determined yet. It is also known that dopamine induces LA vasorelaxation, however, the subtypes of dopamine receptors involved in this mechanism have not yet been identified.Objective. To assess the morphology of nerve fibers and ganglia in the periarterial adipose tissue of the PA bifurcation in patients with and without PH. Design and m

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Yang, Quan-en, Andrew G. Stephen, Joseph W. Adelsberger, et al. "Discovery of Small-Molecule Human Immunodeficiency Virus Type 1 Entry Inhibitors That Target the gp120-Binding Domain of CD4." Journal of Virology 79, no. 10 (2005): 6122–33. http://dx.doi.org/10.1128/jvi.79.10.6122-6133.2005.

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ABSTRACT The interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the CD4 receptor is highly specific and involves relatively small contact surfaces on both proteins according to crystal structure analysis. This molecularly conserved interaction presents an excellent opportunity for antiviral targeting. Here we report a group of pentavalent antimony-containing small molecule compounds, NSC 13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1 strains into CD4+ cells but sho

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Mackay, Simon P., and Patrick J. O’Malley. "Molecular Modelling of the Interaction of Cyanoacrylate Inhibitors with Photosystem II Part 1. The Effect of Hydrophobicity of Inhibitor Binding." Zeitschrift für Naturforschung C 48, no. 9-10 (1993): 773–81. http://dx.doi.org/10.1515/znc-1993-9-1015.

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Abstract Cyanoacrylate Inhibitors, Photosystem II, Hydrophobicity The secondary quinone binding site of photosystem II is also the binding site for many dif ferent herbicides. The 2-cyanoacrylate inhibitors are a potent class of electron transfer inhibitors which bind at this site and are extremely sensitive to minor structural variation. In order to understand their mode of binding, we have studied the interaction between the inhibitors and receptor in the D1 protein binding region (residues Leu 210 to Val 280) in terms of non bonded intermolecular forces. The intermolecular energy was cal

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Lewis, C. A., and D. S. Faber. "Properties of spontaneous inhibitory synaptic currents in cultured rat spinal cord and medullary neurons." Journal of Neurophysiology 76, no. 1 (1996): 448–60. http://dx.doi.org/10.1152/jn.1996.76.1.448.

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1. To identify the type(s) and properties of inhibitory postsynaptic receptor(s) involved in synaptic transmission in cultured rat embryonic spinal cord and medullary neurons, we have used whole cell patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in the presence of tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. 2. The mIPSCs recorded from both spinal cord and medullary neurons had skewed amplitude distributions. 3. The glycinergic antagonist strychnine and the GABAergic antagonist bicuculline each decreased both

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Thompson, Peter, Jinhua Lu, and Gerardo G. Kaplan. "The Cys-Rich Region of Hepatitis A Virus Cellular Receptor 1 Is Required for Binding of Hepatitis A Virus and Protective Monoclonal Antibody 190/4." Journal of Virology 72, no. 5 (1998): 3751–61. http://dx.doi.org/10.1128/jvi.72.5.3751-3761.1998.

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ABSTRACT The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA codes for a class I integral membrane glycoprotein, termed havcr-1, of unknown natural function which serves as an African green monkey kidney (AGMK) cell receptor for HAV. The extracellular domain of havcr-1 has an N-terminal Cys-rich region that displays homology with sequences of members of the immunoglobulin superfamily, followed by a Thr/Ser/Pro (TSP)-rich region characteristic of mucin-like O-glycosylated proteins. The havcr-1 glycoprotein contains four putative N-glycosylation sites, two in the Cys-rich region and two in

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Weinberger, P., P. Kountourakis, C. Sasaki, et al. "Oropharyngeal squamous cell cancers (OSCC) bearing transcriptionally active human papillomavirus (HPV) display distinct protein expression profile." Journal of Clinical Oncology 24, no. 18_suppl (2006): 10028. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10028.

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10028 Background: It is known that among HPV DNA+ OSCCs only the transcriptionally active ones are biologically and clinically relevant. pRb downregulation by HPVE7 results in p16 upregulation. We previously showed (JCO, Feb 2006) that p16 expression defines transcriptionally active HPV+ tumors. Thus, OSCC tumors can be Class I: HPV−/p16−, Class II: HPV+/p16−, or Class III: HPV+/p16+. We hypothesized that tumors classified by these criteria would show different protein expression profiles. Methods: Following institutional review board approval, paraffin-embedded specimens from 77 patients were

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Singh, Amareshwar T. K., Mistuni Ghosh, C. Shad Thaxton, Trudy M. Forte, Robert O. Ryan, and Leo I. Gordon. "The Bioactive Polyphenol Curcumin (diferuloylmethane) In Human Apolipoprotein A-1 Nanodisks Enhances Apoptosis and G1 Cell Cycle Arrest In Mantle Cell Lymphoma Compared with Free Curcumin." Blood 116, no. 21 (2010): 3934. http://dx.doi.org/10.1182/blood.v116.21.3934.3934.

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Abstract Abstract 3934 Background: Mantle cell lymphoma (MCL) is a pre–germinal center neoplasm characterized by cyclin D1 overexpression resulting from translocation of the cyclin D1 gene on 11q13 to the promoter of the immunoglobulin heavy chain locus on 14q32. Since MCL is incurable with standard lymphoma therapies, new treatment approaches are needed that target specific biologic pathways. The bioactive polyphenol curcumin (Curc), derived from the rhizome of Curcuma longa Linn, has been shown to have pleiotropic activities related to its complex chemistry and its influence on multiple sign

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Klasa, Richard J., Alan F. List, and Bruce D. Cheson. "Rational Approaches to Design of Therapeutics Targeting Molecular Markers." Hematology 2001, no. 1 (2001): 443–62. http://dx.doi.org/10.1182/asheducation-2001.1.443.

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Abstract This paper introduces novel therapeutic strategies focusing on a molecular marker relevant to a particular hematologic malignancy. Four different approaches targeting specific molecules in unique pathways will be presented. The common theme will be rational target selection in a strategy that has reached the early phase of human clinical trial in one malignancy, but with a much broader potential applicability to the technology. In Section I Dr. Richard Klasa presents preclinical data on the use of antisense oligonucleotides directed at the bcl-2 gene message to specifically downregula

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Schroeder, Frederick A., Krista L. Penta, Anouch Matevossian, et al. "Drug-Induced Activation of Dopamine D1 Receptor Signaling and Inhibition of Class I/II Histone Deacetylase Induce Chromatin Remodeling in Reward Circuitry and Modulate Cocaine-Related Behaviors." Neuropsychopharmacology 33, no. 12 (2008): 2981–92. http://dx.doi.org/10.1038/npp.2008.15.

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Aiello, Aurora, Giuseppe Pandini, Francesco Frasca та ін. "Peroxisomal Proliferator-Activated Receptor-γ Agonists Induce Partial Reversion of Epithelial-Mesenchymal Transition in Anaplastic Thyroid Cancer Cells". Endocrinology 147, № 9 (2006): 4463–75. http://dx.doi.org/10.1210/en.2005-1610.

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Anaplastic thyroid cancer (ATC) is an extremely aggressive tumor characterized by marked epithelial mesenchymal transition, which leads, almost invariably, to death. Peroxisomal proliferator-activated receptor (PPAR)-γ agonists have recently emerged as potential antineoplastic drugs. To establish whether ATC could be a target of PPARγ agonists, we first examined PPARγ protein expression in a panel of six ATC cell lines and then studied the biologic effects of two PPARγ agonists, ciglitazone and rosiglitazone, that belong to the class of thiazolidonediones. PPARγ protein was present and functio

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Bäsecke, Jörg, Anneke Lehmann, Ulla Bergholz та ін. "The Glycogensynthase Kinase 3b (GSK-3β) Is Involved in Leukemic Transformation". Blood 112, № 11 (2008): 4489. http://dx.doi.org/10.1182/blood.v112.11.4489.4489.

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Abstract Purpose: Signal transduction pathways, such as the PI3K/AKT cascade, are frequently activated in acute myeloid leukemia and stimulate the proliferation and survival of leukemic cells. Mutations in upstream genes such as Class III receptor tyrosine kinases are frequent but not exclusive causes of that activation. An important downstream target of PI3K/AKT is the key regulator GSK-3β. It controls anti-apoptotic genes such as NF-kappaB and Cyclin D1, is involved in wnt-pathway activation and drug resistance of leukemic cells. Deregulated signaling by GSK-3β occurs through inhibition by A

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Wang, Qinghua, Jing Tang, Shujun Jiang та ін. "Inhibition of PPARγ, adipogenesis and insulin sensitivity by MAGED1". Journal of Endocrinology 239, № 2 (2018): 167–80. http://dx.doi.org/10.1530/joe-18-0349.

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Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipogenesis and a target of the thiazolidinedione (TZD) class of antidiabetic drugs; therefore, identifying novel regulators of PPARγ action in adipocytes is essential for the future development of therapeutics for diabetes. MAGE family member D1 (MAGED1), by acting as an adaptor for ubiquitin-dependent degradation pathways and a co-factor for transcription, plays an important role in neural development, cell differentiation and circadian rhythm. Here, we showed that MAGED1 expression was downregulated during adipog

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Zhou, Yixin, Linhua Jin, Stefania Pittaluga, Mark Raffeld, Takashi Miida, and Yoko Tabe. "PI3K a Selective Inhibitor Induces Growth Inhibition In Mantle Cell Lymphoma." Blood 116, no. 21 (2010): 1812. http://dx.doi.org/10.1182/blood.v116.21.1812.1812.

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Abstract Abstract 1812 Deregulation of the phosphatidylinositol 3-kinase (PI3K)-mediated signaling plays an important role in the development of cell proliferation of mantle cell lymphoma (MCL). The PI3K pathway activation in MCL has been shown to result from constitutive B cell receptor (BCR) activation which is directly mediated by the Class IA PI3K p110 isoforms (a, β, and d). However, their relative contribution in MCL is not fully understood. In this study, the activity and molecular mechanisms of isoform-selective PI3K inhibitors which target different isoforms of the p110-kDa subunit ha

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Slater, Alexandre, Ying Di, Joanne C. Clark, et al. "Structural characterization of a novel GPVI-nanobody complex reveals a biologically active domain-swapped GPVI dimer." Blood 137, no. 24 (2021): 3443–53. http://dx.doi.org/10.1182/blood.2020009440.

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Abstract Glycoprotein VI (GPVI) is the major signaling receptor for collagen on platelets. We have raised 54 nanobodies (Nb), grouped into 33 structural classes based on their complementary determining region 3 loops, against recombinant GPVI-Fc (dimeric GPVI) and have characterized their ability to bind recombinant GPVI, resting and activated platelets, and to inhibit platelet activation by collagen. Nbs from 6 different binding classes showed the strongest binding to recombinant GPVI-Fc, suggesting that there was not a single dominant class. The most potent 3, Nb2, 21, and 35, inhibited coll

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Sloand, Elaine M., Katayoun Rezvani, Agnes Yong, et al. "Cytotoxic CD8 T Cell Immune Responses to Wilms Tumor Protein (WT-1) Characterizes Immunosuppression-Responsive Myelodysplasia (MDS)." Blood 108, no. 11 (2006): 849. http://dx.doi.org/10.1182/blood.v108.11.849.849.

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Abstract Clinical observations and experimental evidence link bone marrow failure in myelodysplastic syndrome (MDS) with a T cell-dominated immunologically-mediated pathophysiology in some patients. Indeed, among 129 patients treated with immunosuppression at NIH, trisomy 8 was associated with hematologic response to immunosuppression. We have demonstrated that trisomy 8 patients have oligoclonal CD8 T cell expansion, as determined by increased proportions of one or more T cell receptor (TCR) V beta subfamilies (Sloand et al. Blood106:841; 2005) which had cytotoxic activity toward trisomy 8 ce

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Malkovsky, M., D. G. McNeel, M. Wallace та ін. "Use of zoledronic acid (ZA) and interleukin-2 (IL-2) to activate and expand Vγ9Vδ2 T cells for therapeutic use in patients with metastatic renal cell carcinoma (mRCC)". Journal of Clinical Oncology 24, № 18_suppl (2006): 14607. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14607.

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14607 Background: Approximately 3–6% of human peripheral blood lymphocytes express the γδ T cell receptor (TCR). The majority of these cells express the Vδ2 TCR variable segment associated with the Vγ9 segment. Vγ9Vδ2 T cells can recognize phosphorylated nonpeptidic microbial metabolites and alkylamines. This recognition of phosphorylated molecules requires neither antigen uptake/processing, nor MHC class I/II expression, allowing for a rapid response to immune challenge. Aminobisphosphonates are a class of agents capable of activating human Vγ9Vδ2 T cells. Here we conduct a study using ZA wit

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Cichocki, Frank M., Todd Lenvik, Stephen K. Anderson, and Jeffrey S. Miller. "STAT5A Overexpression Enhances Killer Immunoglobulin Receptor (KIR) Expression in Developing NK Cells and Is Associated with a Loss of Reverse Transcription from the Proximal KIR Promoter." Blood 110, no. 11 (2007): 798. http://dx.doi.org/10.1182/blood.v110.11.798.798.

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Abstract Down-regulation of HLA-class I molecules is commonly observed in virally infected and malignantly transformed cells and can contribute to the ability of these cells to escape recognition by the adaptive immune system. NK cells are able to detect the loss of even single HLA alleles on potential target cells through their clonally distributed HLA-class I-specific inhibitory receptors (KIR). While it is well established that individual KIR gene expression is strongly correlated with the DNA methylation status of CpG dinucleotides in areas surrounding the transcription initiation region,

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Duhoux, Francois P., Agnes Jager, Luc Dirix, et al. "Combination of paclitaxel and LAG3-Ig (IMP321), a novel MHC class II agonist, as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Interim results from the run-in phase of a placebo controlled randomized phase II." Journal of Clinical Oncology 35, no. 15_suppl (2017): 1062. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1062.

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1062 Background: IMP321 is a recombinant soluble LAG3-Ig fusion protein that binds to MHC class II molecules and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. The activation of the dendritic cell network with IMP321 the day after a low dose injection of a single agent chemotherapy may lead to stronger anti-tumor CD8 T-cell responses. We report initial results of the safety run-in of a randomized, placebo-controlled phase IIb trial in patients (pts) with hormone receptor positive (HR+) MBC receiving first-line weekly paclitaxel. Methods: In the safety run-

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Meachem, Sarah J., Saleela M. Ruwanpura, Jessica Ziolkowski, Jacquelyn M. Ague, Michael K. Skinner, and Kate L. Loveland. "Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation." Journal of Endocrinology 186, no. 3 (2005): 429–46. http://dx.doi.org/10.1677/joe.1.06121.

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The critical influence of follicle stimulating hormone (FSH) on male fertility relates both to its impact on Sertoli cell proliferation in perinatal life and to its influence on the synthesis of Sertoli cell-derived products essential for germ cell survival and function in the developing adult testis. The nature and timing of this shift of germ cells to their reliance on specific Sertoli cell-derived products are not defined. Based on existing data, it is apparent that the dominant function of FSH shifts between 9 and 18 day postpartum (dpp) during the first wave of spermatogenesis from drivin

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Sloand, Elaine M., Katayoun Rezvani, John Barrett, et al. "Myelodysplasia with Trisomy 8 Is Associated with a Cytotoxic CD8 T Cell Immune Response to Wilms Tumor-1 Protein (WT1)." Blood 104, no. 11 (2004): 474. http://dx.doi.org/10.1182/blood.v104.11.474.474.

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Abstract Clinical observations and experimental evidence link bone marrow failure in myelodysplastic syndrome (MDS) with a T cell-dominated autoimmune process in some patients. Among 133 patients treated at NIH, predominantly with antithymocyte globulin, trisomy 8 as the sole karyotypic abnormality was specifically and significantly associated with favorable hematologic response to immunosuppresssion, as compared to patients with other cytogenetic abnormalities or with a normal karyotype. Trisomy 8 MDS patients show stable increases in the proportion of aneuploid bone marrow cells following im

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Moratalla, Rosario, Mario Vallejo, Bulent Elibol, and Ann M. Graybiel. "D1-class dopamine receptors influence cocaine-induced persistent expression of Fos-related proteins in striatum." NeuroReport 8, no. 1 (1996): 1–5. http://dx.doi.org/10.1097/00001756-199612200-00001.

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Smith, Porsha L., Fengting Yan, John T. Patton, et al. "PRMT5 Transgenic Mice Develop Aggressive Lymphoblastic Lymphomas." Blood 128, no. 22 (2016): 2936. http://dx.doi.org/10.1182/blood.v128.22.2936.2936.

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Abstract Introduction: Emerging data collected from whole genome and epigenomic studies in solid and blood cancers has pointed toward dysregulation of chromatin remodelers as a unique class of cancer drivers. Next generation sequencing of lymphoma has identified several mutations affecting enzymes that regulate epigenetic control of gene expression. The epigenetic modifier protein arginine methyltransferase 5 (PRMT5) that has been shown to be essential for Epstein-Barr virus-driven B-cell transformation, is overexpressed in several histologic subtypes of B-cell non-Hodgkin's lymphomas (NHL) an

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Vanover, Kimberly, Steven Glass, Susan Kozauer, et al. "30 Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study." CNS Spectrums 24, no. 1 (2019): 190–91. http://dx.doi.org/10.1017/s1092852919000245.

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AbstractBackgroundLumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems. Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.MethodsLumateperone was evaluated in 3 controlled

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Kapuria, Vaibhav, Geoffrey Bartholomeusz, Ling-Yuan Kong, et al. "A Novel Small-Molecule Approach To Inhibit Jak2 Tyrosine Kinase Signaling." Blood 110, no. 11 (2007): 1556. http://dx.doi.org/10.1182/blood.v110.11.1556.1556.

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Abstract Jak kinases are non-receptor protein tyrosine kinases that play a pivotal role in cytokine/growth factor signaling through phosphorylation of specific proteins such as the Stat molecules. Activated Stats translocate to the nucleus where they mediate transcription of several target genes involved in cell cycle progression and survival (Bcl-xL, cyclin D1, c-myc, survivin. Many tumors have highly activated Stats that are associated with aberrant Jak2 regulation and recent studies have shown that activating mutations in Jak2 (V617F) play a key role in many myeloproliferative disorders suc

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