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1369 records – page 1 of 137.

2-substituted 1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. A new class of antitumor agent.

https://arctichealth.org/en/permalink/ahliterature24099
Source
J Med Chem. 1993 Mar 19;36(6):765-70
Publication Type
Article
Date
Mar-19-1993
Author
S M Sami
R T Dorr
D S Alberts
W A Remers
Author Affiliation
Department of Pharmaceutical Sciences and Cancer Center, University of Arizona, Tucson 85721.
Source
J Med Chem. 1993 Mar 19;36(6):765-70
Date
Mar-19-1993
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - chemical synthesis - chemistry - therapeutic use
Female
Humans
Isoquinolines - chemical synthesis - chemistry - therapeutic use
Leukemia L1210 - drug therapy
Leukemia P388 - drug therapy
Male
Melanoma, Experimental - drug therapy
Mice
Mice, Inbred DBA
Ovarian Neoplasms - drug therapy
Research Support, U.S. Gov't, P.H.S.
Structure-Activity Relationship
Tumor Cells, Cultured - drug effects
Abstract
A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2-(dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side-chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants.
PubMed ID
8459403 View in PubMed
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5-aminolevulinic acid mediated photodynamic therapy of Lewis lung carcinoma: a role of tumor infiltration with different cells of immune system.

https://arctichealth.org/en/permalink/ahliterature17286
Source
Exp Oncol. 2004 Dec;26(4):312-5
Publication Type
Article
Date
Dec-2004
Author
Larisa M Skivka
Oksana B Gorobets
Vadim V Kutsenok
Miron O Lozinsky
Anatoliy N Borisevich
Alexander G Fedorchuk
Vladimir V Kholin
Nikolai F Gamaleya
Author Affiliation
T.G. Shevchenko Kyiv National University, Kyiv, Ukraine. realmed@i.com.ua
Source
Exp Oncol. 2004 Dec;26(4):312-5
Date
Dec-2004
Language
English
Publication Type
Article
Keywords
Aminolevulinic Acid - pharmacology
Animals
Carcinoma, Lewis Lung - pathology
Dose-Response Relationship, Drug
Immunologic Factors
Lymphocytes - physiology
Male
Mice
Mice, Inbred C57BL
Monocytes - physiology
Photochemotherapy
Photosensitizing Agents - pharmacology
Abstract
AIM: To investigate the effect of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) as a photosensitizer on the character of infiltration of experimental tumors by different cells of immune system. METHODS: The effect of ALA-PDT on subcutaneously implanted Lewis lung carcinoma in c57Bl/6 mice was studied. ALA at a dose of 500 mg/kg was given per os, and 4 h later tumors were subjected to laser irradiation (632 nm, 150 mW/cm(2), 20 min). The evaluation of the tumor infiltration by myelomonocytic and lymphoid cells and oxygen-dependent metabolism of peritoneal macrophages (NBT-test) were carried out. RESULTS: It is shown that ALA-PDT resulted in fast and massive infiltration of irradiated tumors by myelomonocytic cells, stimulation of the peritoneal macrophages metabolic activity and augmentation of the content of tumor infiltrating lymphocytes. CONCLUSION: The immunomodulation after ALA-PDT occurs via generation of inflammation and direct laser light activation of immune system cells.
PubMed ID
15627065 View in PubMed
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5-HT(1A) receptor antagonist p-MPPI attenuates acute ethanol effects in mice and rats.

https://arctichealth.org/en/permalink/ahliterature9998
Source
Neurosci Lett. 2002 Mar 29;322(1):1-4
Publication Type
Article
Date
Mar-29-2002
Author
Nina K Popova
Elena A Ivanova
Author Affiliation
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Lavrentyeva 10, 630090 Novosibirsk, Russia. npopova@bionet.nsc.ru
Source
Neurosci Lett. 2002 Mar 29;322(1):1-4
Date
Mar-29-2002
Language
English
Publication Type
Article
Keywords
Acute Disease
Alcohol-Induced Disorders, Nervous System - drug therapy - metabolism - physiopathology
Aminopyridines - pharmacology
Animals
Brain - drug effects - metabolism - physiopathology
Dose-Response Relationship, Drug
Drug Interactions - physiology
Drug Tolerance - physiology
Ethanol - pharmacology
Hypothermia - chemically induced - drug therapy - physiopathology
Male
Mice
Mice, Inbred C3H
Neurons - drug effects - metabolism
Piperazines - pharmacology
Rats
Rats, Wistar
Receptors, Serotonin - drug effects - metabolism
Receptors, Serotonin, 5-HT1
Research Support, Non-U.S. Gov't
Serotonin - metabolism
Serotonin Antagonists - pharmacology
Sleep - drug effects - physiology
Startle Reaction - drug effects - physiology
Abstract
The effect of a selective 5-HT(1A) antagonist, 4-(2'-methoxy-)phenyl-1-[2'-(N-2"-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI), on acute ethanol-induced hypothermia, sleep and suppression of acoustic startle reflex in C3H/He mice and Wistar rats was studied. Administration of p-MPPI at the doses of 0.4, 0.7 and 1.0 mg/kg reduced in a dose-dependent manner the ethanol-induced hypothermia and the sleep time and attenuated the ethanol-induced decrease of acoustic startle reflex magnitude in mice. Similar p-MPPI (0.4 mg/kg) effects on ethanol-induced sleep and hypothermia were obtained in rats. It was concluded that 5-HT(1A) receptors were involved in the mechanisms of the ethanol-induced hypothermia and sleep, and that 5-HT(1A) antagonist increased acute ethanol tolerance.
PubMed ID
11958829 View in PubMed
Less detail

6- and 7-substituted 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h] isoquinoline-1,3-diones: synthesis, nucleophilic displacements, antitumor activity, and quantitative structure-activity relationships.

https://arctichealth.org/en/permalink/ahliterature22674
Source
J Med Chem. 1996 Apr 12;39(8):1609-18
Publication Type
Article
Date
Apr-12-1996
Author
S M Sami
R T Dorr
A M Sòlyom
D S Alberts
B S Iyengar
W A Remers
Author Affiliation
Department of Pharmacology and Toxicology, University of Arizona, Tucson, 85721, USA.
Source
J Med Chem. 1996 Apr 12;39(8):1609-18
Date
Apr-12-1996
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - chemical synthesis - pharmacology
Humans
Isoquinolines - chemical synthesis
Male
Mice
Mice, Inbred DBA
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Structure-Activity Relationship
Tumor Cells, Cultured
Abstract
New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells including human melanoma and ovarian cancer and murine sensitive and MDR L1210 leukemia. They also were less cardiotoxic in cell culture. Four of these compounds were not cross-resistant with the MDR leukemia, and one of them, 6-ethoxyazonafide, was nearly as potent against solid tumor cells as leukemia cells. These compounds also had good potency against human breast, colon, and lung cancer cells, including doxorubicin and mitoxantrone resistant cell lines. Advantages of the new analogues over azonafide were less in vivo, but 6-ethoxyazonafide was more effective against L1210 leukemia and subcutaneous B16 melanoma in mice. Although correlations of antitumor potency in cells and physicochemical properties of substituents were not found, there were statistically significant correlations of DNA melt transition temperature (delta Tm) with potency in solid tumor cells and sensitive and MDR resistant L1210 leukemia cells for 6-substituted azonafides and with solid tumors for 7-substituted azonafides.
PubMed ID
8648600 View in PubMed
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7-Alkoxyquinoline O-dealkylation by microsomes from human liver and placenta.

https://arctichealth.org/en/permalink/ahliterature64902
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Publication Type
Article
Date
Nov-1992
Author
J. Hakkola
J. Mäenpää
R T Mayer
S S Park
H V Gelboin
O. Pelkonen
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Date
Nov-1992
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - diagnostic use
Benzyl Compounds - metabolism
Cytochrome P-450 Enzyme System - antagonists & inhibitors - metabolism
Dealkylation
Female
Humans
In Vitro
Male
Mice
Mice, Inbred Strains
Microsomes - enzymology - metabolism
Microsomes, Liver - enzymology - metabolism
Placenta - enzymology - metabolism
Pregnancy
Quinolines - metabolism
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Smoking - metabolism
Abstract
1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
PubMed ID
1467136 View in PubMed
Less detail

99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: immune therapies of type 1 diabetes: new opportunities based on the hygiene hypothesis.

https://arctichealth.org/en/permalink/ahliterature144028
Source
Clin Exp Immunol. 2010 Apr;160(1):106-12
Publication Type
Article
Date
Apr-2010
Author
L. Chatenoud
S. You
H. Okada
C. Kuhn
B. Michaud
J-F Bach
Author Affiliation
Université Paris Descarte, Paris, France. lucienne.chatenoud@inserm.fr
Source
Clin Exp Immunol. 2010 Apr;160(1):106-12
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Adolescent
Animals
Autoantigens - immunology
Bacteria - immunology
Canada - epidemiology
Child
Diabetes Mellitus, Type 1 - immunology - therapy
Europe - epidemiology
Humans
Hygiene
Hypersensitivity - immunology
Immunosuppression - methods
Immunotherapy - methods
Infection - immunology - microbiology
Mice
Pancreatitis - immunology - microbiology
Toll-Like Receptors - agonists
Young Adult
Abstract
Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting beta cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4(+) and CD8(+) T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the 'hygiene hypothesis', which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically.
Notes
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PubMed ID
20415859 View in PubMed
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1992 Genetics Society of Canada Award of Excellence Lecture: Genes, science, and society.

https://arctichealth.org/en/permalink/ahliterature220545
Source
Genome. 1993 Aug;36(4):631-40
Publication Type
Article
Date
Aug-1993
Author
C R Scriver
Author Affiliation
DeBelle Laboratory, McGill University-Montreal Children's Hospital Research Institute, QC, Canada.
Source
Genome. 1993 Aug;36(4):631-40
Date
Aug-1993
Language
English
Publication Type
Article
Keywords
Amino Acid Metabolism, Inborn Errors - genetics - history
Animals
Awards and Prizes
Canada
Child
Disease Models, Animal
Female
Genetics - history
History, 20th Century
Humans
Male
Mice
Rickets - genetics - history
Social Environment
Societies, Scientific
PubMed ID
8405982 View in PubMed
Less detail

Aberrant iNOS signaling is under genetic control in rodent liver cancer and potentially prognostic for the human disease.

https://arctichealth.org/en/permalink/ahliterature92898
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Publication Type
Article
Date
Aug-2008
Author
Calvisi Diego F
Pinna Federico
Ladu Sara
Pellegrino Rossella
Muroni Maria R
Simile Maria M
Frau Maddalena
Tomasi Maria L
De Miglio Maria R
Seddaiu Maria A
Daino Lucia
Sanna Valeria
Feo Francesco
Pascale Rosa M
Author Affiliation
Department of Biomedical Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy.
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Date
Aug-2008
Language
English
Publication Type
Article
Keywords
Animals
Carcinoma, Hepatocellular - enzymology - epidemiology - genetics - pathology
Cell Line, Tumor
Genetic Predisposition to Disease
Humans
Incidence
Liver Neoplasms - enzymology - epidemiology - genetics - pathology
Male
Mice
Mice, Transgenic
Nitric Oxide Synthase Type II - genetics
Prognosis
Rats
Rats, Inbred BN
Rats, Inbred F344
Signal Transduction - physiology
Abstract
Mounting evidence underlines the role of inducible nitric oxide synthase (iNOS) in hepatocellular carcinoma (HCC) development, but its functional interactions with pathways involved in HCC progression remain uninvestigated. Here, we analyzed in preneoplastic and neoplastic livers from Fisher 344 and Brown Norway rats, possessing different genetic predisposition to HCC, in transforming growth factor-alpha (TGF-alpha) and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (i) iNOS function and interactions with nuclear factor-kB (NF-kB) and Ha-RAS/extracellular signal-regulated kinase (ERK) during hepatocarcinogenesis; (ii) influence of genetic predisposition to liver cancer on these pathways and role of these cascades in determining a susceptible or resistant phenotype and (iii) iNOS prognostic value in human HCC. We found progressive iNos induction in rat and mouse liver lesions, always at higher levels in the most aggressive models represented by HCC of rats genetically susceptible to hepatocarcinogenesis and c-Myc-TGF-alpha transgenic mice. iNOS, inhibitor of kB kinase/NF-kB and RAS/ERK upregulation was significantly higher in HCC with poorer prognosis (as defined by patients' survival length) and positively correlated with tumor proliferation, genomic instability and microvascularization and negatively with apoptosis. Suppression of iNOS signaling by aminoguanidine led to decreased HCC growth and NF-kB and RAS/ERK expression and increased apoptosis both in vivo and in vitro. Conversely, block of NF-kB signaling by sulfasalazine or short interfering RNA (siRNA) or ERK signaling by UO126 caused iNOS downregulation in HCC cell lines. These findings indicate that iNOS cross talk with NF-kB and Ha-RAS/ERK cascades influences HCC growth and prognosis, suggesting that key component of iNOS signaling could represent important therapeutic targets for human HCC.
PubMed ID
18579559 View in PubMed
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Abeta oligomer-mediated long-term potentiation impairment involves protein phosphatase 1-dependent mechanisms.

https://arctichealth.org/en/permalink/ahliterature162439
Source
J Neurosci. 2007 Jul 18;27(29):7648-53
Publication Type
Article
Date
Jul-18-2007
Author
Marlen Knobloch
Mélissa Farinelli
Uwe Konietzko
Roger M Nitsch
Isabelle M Mansuy
Author Affiliation
Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
Source
J Neurosci. 2007 Jul 18;27(29):7648-53
Date
Jul-18-2007
Language
English
Publication Type
Article
Keywords
Age Factors
Amyloid Precursor Protein Secretases - genetics
Amyloid beta-Peptides - chemistry - metabolism - ultrastructure
Analysis of Variance
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Dose-Response Relationship, Radiation
Electric Stimulation - methods
Excitatory Postsynaptic Potentials - drug effects - physiology
Gene Expression Regulation - genetics
Hippocampus - cytology
Humans
Long-Term Potentiation - genetics - physiology - radiation effects
Mice
Mice, Transgenic
Microscopy, Electron, Transmission - methods
Neurons - drug effects - physiology
Patch-Clamp Techniques
Phosphoprotein Phosphatases - physiology
Presenilin-1 - genetics
Protein Phosphatase 1
Reverse Transcriptase Polymerase Chain Reaction - methods
Abstract
Amyloid beta (Abeta) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions are complex and not fully understood. Here, we provide the first evidence that these mechanisms involve protein phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with the Swedish and Arctic mutations that render Abeta more prone to form oligomers (arcAbeta mice), we show that the LTP impairment induced by Abeta oligomers can be fully reversed by PP1 inhibition in vitro. We further demonstrate that the genetic inhibition of endogenous PP1 in vivo confers resistance to Abeta oligomer-mediated toxicity and preserves LTP. Overall, these results reveal that PP1 is a key player in the mechanisms of AD pathology.
PubMed ID
17634359 View in PubMed
Less detail

Abnormal adherence junctions in the heart and reduced angiogenesis in transgenic mice overexpressing mutant type XIII collagen.

https://arctichealth.org/en/permalink/ahliterature53860
Source
EMBO J. 2001 Sep 17;20(18):5153-64
Publication Type
Article
Date
Sep-17-2001
Author
M. Sund
R. Ylönen
A. Tuomisto
R. Sormunen
J. Tahkola
A P Kvist
S. Kontusaari
H. Autio-Harmainen
T. Pihlajaniemi
Author Affiliation
Collagen Research Unit, Biocenter Oulu, Department of Medical Biochemistry, University of Oulu, PL 5000, 90014 Oulu, Finland.
Source
EMBO J. 2001 Sep 17;20(18):5153-64
Date
Sep-17-2001
Language
English
Publication Type
Article
Keywords
Adherens Junctions - ultrastructure
Animals
Collagen - genetics - metabolism - physiology
Embryonic and Fetal Development
Fetus - abnormalities - blood supply
Heart - embryology
Heart Defects, Congenital - pathology
Mice
Mice, Transgenic
Mutation
Myocardium - ultrastructure
Neovascularization, Physiologic
Phenotype
Placenta - abnormalities - blood supply
RNA, Messenger - biosynthesis
Research Support, Non-U.S. Gov't
Survival Analysis
Abstract
Type XIII collagen is a type II transmembrane protein found at sites of cell adhesion. Transgenic mouse lines were generated by microinjection of a DNA construct directing the synthesis of truncated alpha1(XIII) chains. Shortened alpha 1(XIII) chains were synthesized by fibroblasts from mutant mice, and the lack of intracellular accumulation in immunofluorescent staining of tissues suggested that the mutant molecules were expressed on the cell surface. Transgene expression led to fetal lethality in offspring from heterozygous mating with two distinct phenotypes. The early phenotype fetuses were aborted by day 10.5 of development due to a lack of fusion of the chorionic and allantoic membranes. The late phenotype fetuses were aborted by day 13.5 of development and displayed a weak heartbeat, defects of the adherence junctions in the heart with detachment of myofilaments and abnormal staining for the adherence junction component cadherin. Decreased microvessel formation was observed in certain regions of the fetus and the placenta. These results indicate that type XIII collagen has an important role in certain adhesive interactions that are necessary for normal development.
PubMed ID
11566879 View in PubMed
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1369 records – page 1 of 137.