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Article ; Online: Drug abuse and the neurovascular unit.

Egleton, Richard D / Abbruscato, Thomas

Advances in pharmacology (San Diego, Calif.)

2014 Volume 71, Page(s) 451–480

Abstract: Drug abuse continues to create a major international epidemic affecting society. A great majority of past drug abuse research has focused mostly on the mechanisms of addiction and the specific effects of substance use disorders on brain circuits and ... ...

Abstract	Drug abuse continues to create a major international epidemic affecting society. A great majority of past drug abuse research has focused mostly on the mechanisms of addiction and the specific effects of substance use disorders on brain circuits and pathways that modulate reward, motivation, craving, and decision making. Few studies have focused on the neurobiology of acute and chronic substance abuse as it relates to the neurovascular unit (brain endothelial cell, neuron, astrocyte, microglia, and pericyte). Increasing research indicates that all cellular components of the neurovascular unit play a pivotal role in both the process of addiction and how drug abuse affects the brain response to diseases. This review will focus on the specific effects of opioids, amphetamines, alcohol, and nicotine on the neurovascular unit and its role in addiction and adaption to brain diseases. Elucidation of the role of the neurovascular unit on the neurobiology associated with drug addiction will help to facilitate the development of better therapeutic approaches for drug-dependent individuals.
MeSH term(s)	Amphetamines/pharmacology ; Analgesics, Opioid/pharmacology ; Animals ; Brain/cytology ; Brain/drug effects ; Brain/metabolism ; Ethanol/pharmacology ; Humans ; Nicotine/pharmacology ; Substance-Related Disorders/metabolism ; Substance-Related Disorders/pathology
Chemical Substances	Amphetamines ; Analgesics, Opioid ; Ethanol (3K9958V90M) ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1557-8925
ISSN (online)	1557-8925
DOI	10.1016/bs.apha.2014.06.019
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Article: Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure.

Boggess, Taylor / Williamson, James C / Niebergall, Ethan B / Sexton, Hannah / Mazur, Anna / Egleton, Richard D / Grover, Lawrence M / Risher, W Christopher

Frontiers in pediatrics

2021 Volume 9, Page(s) 794544

Abstract: The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of ... ...

Abstract	The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca
Language	English
Publishing date	2021-12-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.794544
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Article ; Online: Peptides at the blood brain barrier: Knowing me knowing you.

Davis, Thomas P / Abbruscato, Thomas J / Egleton, Richard D

Peptides

2015 Volume 72, Page(s) 50–56

Abstract: When the Davis Lab was first asked to contribute to this special edition of Peptides to celebrate the career and influence of Abba Kastin on peptide research, it felt like a daunting task. It is difficult to really understand and appreciate the influence ...

Abstract	When the Davis Lab was first asked to contribute to this special edition of Peptides to celebrate the career and influence of Abba Kastin on peptide research, it felt like a daunting task. It is difficult to really understand and appreciate the influence that Abba has had, not only on a generation of peptide researchers, but also on the field of blood brain barrier (BBB) research, unless you lived it as we did. When we look back at our careers and those of our former students, one can truly see that several of Abba's papers played an influential role in the development of our personal research programs.
MeSH term(s)	Animals ; Biomedical Research/history ; Blood-Brain Barrier/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; Peptides/history ; Peptides/metabolism ; Protein Transport/physiology
Chemical Substances	Peptides
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2015.04.020
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Zs.A 1649: Show issues

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Article: Pathophysiology of the blood-brain barrier: animal models and methods.

Hawkins, Brian T / Egleton, Richard D

Current topics in developmental biology

2008 Volume 80, Page(s) 277–309

Abstract: The specialized cerebral microvascular endothelium interacts with the cellular milieu of the brain and extracellular matrix to form a neurovascular unit, one aspect of which is a regulated interface between the blood and central nervous system (CNS). The ...

Abstract	The specialized cerebral microvascular endothelium interacts with the cellular milieu of the brain and extracellular matrix to form a neurovascular unit, one aspect of which is a regulated interface between the blood and central nervous system (CNS). The concept of this blood-brain barrier (BBB) as a dynamically regulated system rather than a static barrier has wide-ranging implications for pathophysiology of the CNS. While in vitro models of the BBB are useful for screening drugs targeted to the CNS and indispensable for studies of cerebral endothelial cell biology, the complex interactions of the neurovascular unit make animal-based models and methods essential tools for understanding the pathophysiology of the BBB. BBB dysfunction is a complication of neurodegenerative disease and brain injury. Studies on animal models have shown that diseases of the periphery, such as diabetes and inflammatory pain, have deleterious effects on the BBB which may contribute to neurological complications associated with these conditions. Furthermore, genetic and/or epigenetic abnormalities in constituents of the BBB may be significant contributing factors in disease etiology. Research that approaches the BBB as a dynamic system integrated with both the CNS and the periphery is therefore critical to understanding and treating diseases of the CNS. Herein, we review various methodological approaches used to study BBB function in the context of disease. These include measurement of transport between blood and brain, imaging-based technologies, and genomic/proteomic approaches.
MeSH term(s)	Animals ; Biological Transport, Active ; Biotransformation ; Blood-Brain Barrier/physiology ; Brain/metabolism ; Capillary Permeability ; Central Nervous System Diseases/physiopathology ; Diabetes Mellitus/physiopathology ; Endocytosis ; Genomics ; Humans ; Inflammation/physiopathology ; Models, Animal ; Models, Neurological ; Pain/physiopathology ; Proteomics
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1557-8933 ; 0070-2153
ISSN (online)	1557-8933
ISSN	0070-2153
DOI	10.1016/S0070-2153(07)80007-X
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Article: A paradigm shift for evaluating pharmacotherapy for Alzheimer's disease: the 10-patient screening protocol.

Weinstein, James D / Gonzalez, Edgar R / Egleton, Richard D / Hunt, David A

The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists

2013 Volume 28, Issue 7, Page(s) 443–454

Abstract: Objective: Discuss etiology of Alzheimer's disease (AD) and offer a paradigm shift-a change in basic assumptions-from present standards in clinical trials.: Data source: PubMed search for studies into AD pathophysiology and assessment of disease ... ...

Abstract	Objective: Discuss etiology of Alzheimer's disease (AD) and offer a paradigm shift-a change in basic assumptions-from present standards in clinical trials. Data source: PubMed search for studies into AD pathophysiology and assessment of disease progression. Searched terms: amyloid precursor protein/amyloid beta pathology, senile plaques, mitochondrial dysfunction, reactive oxygen species , advanced glycation end products, neuro-inflammation, dysfunctional microglia/astrocytes, proinflammatory cytokines, ApoE4 allele, Tau phosphorylation, Chlamydia pneumoniae, Dementia Severity Rating Scale, Clinical Dementia Rating Scale, Relative's Assessment of Global Symptomatology-Elderly, and Alzheimer's Disease Assessment Scale-cognitive. Study selection: All prospective, randomized, placebo- or cohort-controlled, peer-reviewed English language publications from 1980 to 2012. Studies in animals, AD patients, and AD brain specimens. Data extraction: Objectives, methods, statistical design, and results reviewed to assess soundness of trials and validity of results. Trials with flawed methods or uninterpretable results excluded. Data synthesis: Primary pathophysiology comprises: amyloid precursor protein/amyloid beta pathology with deposition of senile plaques; mitochondrial dysfunction with insufficient ATP synthesis and release of reactive oxygen species; oxidative stress; and neuro-inflammation from dysfunction of microglia and astrocytes. Other factors include abnormal ApoE4 allele protein and aberrant Tau phosphorylation. Role of Chlamydia pneumoniae is unproven. Dementia Severity Rating Scale (DSRS) is optimal assessment tool for assessing AD progression. Conclusion: AD's complex pathophysiology may require polypharmacy to mitigate symptoms and progression. DSRS-driven, 10-patient pilot studies offer practical, valid, and reliable screening for potentially effective pharmacotherapy in AD. The simplicity of this paradigm shift should expedite research and may promote earlier discovery of effective pharmacotherapy for AD.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Protein Precursor/metabolism ; Humans ; Mitochondria/metabolism ; Oxidative Stress
Chemical Substances	Amyloid beta-Protein Precursor
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1107921-6
ISSN	2331-0936 ; 0888-5109
ISSN (online)	2331-0936
ISSN	0888-5109
DOI	10.4140/TCP.n.2013.443
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Zs.A 3412: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 209: Show issues

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Article: Fluorescence imaging of blood-brain barrier disruption.

Hawkins, Brian T / Egleton, Richard D

Journal of neuroscience methods

2006 Volume 151, Issue 2, Page(s) 262–267

Abstract: Pathological alterations of the blood-brain barrier (BBB) can be topographically heterogeneous. The goal of this study was to develop a method to assess rapidly the magnitude and spatial distribution of permeability changes. Rats were perfused via the ... ...

Abstract	Pathological alterations of the blood-brain barrier (BBB) can be topographically heterogeneous. The goal of this study was to develop a method to assess rapidly the magnitude and spatial distribution of permeability changes. Rats were perfused via the common carotid arteries with Ringer's solution containing sodium fluorescein (NF) and Evans Blue albumin (EB). Global NF uptake was determined by fluorimetry and EB uptake was determined by absorbance spectroscopy. NF uptake was linear in control animals and at a rate comparable to sucrose, whereas uptake of EB was negligible. Infusion of 1.6 M mannitol immediately prior to perfusion significantly increased uptake of NF while EB uptake was unchanged. BBB disruption was confirmed by confocal microscopy of fresh-frozen sections. In control animals, NF and EB staining were limited to the edges of slices and to the circumventricular organs. In mannitol-treated animals, heavy NF staining was observed throughout the brain, and EB staining was localized around some microvessels. In animals given a approximately 500 microl air embolus prior to perfusion, a discrete area of NF and EB staining could be observed near the ventral midline, while the rest of the brain remained unaltered. We find that brain perfusion with NF/EB enables a rapid, reliable, and highly sensitive assessment of global BBB permeability and microscopic visualization of discrete BBB disruptions.
MeSH term(s)	Animals ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/pathology ; Evans Blue/pharmacokinetics ; Fluorescein/pharmacokinetics ; Male ; Metabolic Clearance Rate ; Microscopy, Confocal/methods ; Microscopy, Fluorescence/methods ; Permeability ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Fluorescence/methods
Chemical Substances	Evans Blue (45PG892GO1) ; Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2006-03-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2005.08.006
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Zs.A 1486: Show issues

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Article: Development of neuropeptide drugs that cross the blood-brain barrier.

Egleton, Richard D / Davis, Thomas P

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics

2005 Volume 2, Issue 1, Page(s) 44–53

Abstract: In recent years, there have been several important advancements in the development of neuropeptide therapeutics. Nevertheless, the targeting of peptide drugs to the CNS remains a formidable obstacle. Delivery of peptide drugs is limited by their poor ... ...

Abstract	In recent years, there have been several important advancements in the development of neuropeptide therapeutics. Nevertheless, the targeting of peptide drugs to the CNS remains a formidable obstacle. Delivery of peptide drugs is limited by their poor bioavailability to the brain due to low metabolic stability, high clearance by the liver, and the presence of the blood brain barrier (BBB). Multiple strategies have been devised in an attempt to improve peptide drug delivery to the brain, with variable results. In this review, we discuss several of the strategies that have been used to improve both bioavailability and BBB transport, with an emphasis on antibody based vector delivery, useful for large peptides/small proteins, and glycosylation, useful for small peptides. Further development of these delivery methods may finally enable peptide drugs to be useful for the treatment of neurological disease states.
MeSH term(s)	Animals ; Biological Availability ; Biological Transport, Active/physiology ; Blood-Brain Barrier/physiology ; Brain Chemistry ; Central Nervous System Agents/pharmacokinetics ; Glycosylation ; Humans ; Neuropeptides/pharmacokinetics
Chemical Substances	Central Nervous System Agents ; Neuropeptides
Language	English
Publishing date	2005-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2205033-4
ISSN	1545-5351 ; 1545-5343
ISSN (online)	1545-5351
ISSN	1545-5343
DOI	10.1602/neurorx.2.1.44
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Article ; Online: History of postpartum depression as a contributor to the severity of NAS.

Nellhaus, Emma M / Nieuwenhuizen, Louis / Egleton, Richard / Hansen, Zachary / Chaffin, David / Loudin, Sean / Davies, Todd H

Addictive behaviors

2018 Volume 89, Page(s) 78–84

Abstract: Currently, there are no clinical tools available to accurately predict the severity of neonatal withdrawal. Studies of non-exposed neonates suggest that maternal depression and anxiety are predictive of negative short and long-term neonatal outcomes, but ...

Abstract	Currently, there are no clinical tools available to accurately predict the severity of neonatal withdrawal. Studies of non-exposed neonates suggest that maternal depression and anxiety are predictive of negative short and long-term neonatal outcomes, but research is lacking in the addicted population. We studied of 109 pregnant women in medication-assisted treatment (MAT) and their neonates to determine if psychiatric conditions co-occurring with Substance Use Disorder (SUD) contributed to the severity of neonatal withdrawal. The need for pharmacological intervention, Finnegan scores, length of methadone treatment, and length of hospital stay were used to assess withdrawal severity. Categorical variables were analyzed in Stata14 using Chi Square and continuous variables were analyzed using Wilcoxon Rank Sum. Among the 110 neonates whose outcomes were reviewed, a maternal history of Postpartum Depression (PPD) was found to be correlated with increased severity of withdrawal. The neonates born to mothers with past diagnoses of PPD had more consecutive days of high Finnegan scores (95% confidence interval [CI], P = 0.003), longer length of treatment (95% CI, P = 0.006), and length of hospital stay (95% CI, P = 0.014). There was no apparent relationship between NAS severity and other psychiatric disorders. In a study of pregnant women with SUD and their neonates, we uncovered a relationship between the severity of NAS and maternal history of PPD. Our findings demonstrate that further research into these deleterious outcomes is warranted. Until then, we suggest collection of maternal history of PPD and careful screening for new cases in the SUD population.
MeSH term(s)	Adult ; Depression, Postpartum/epidemiology ; Depression, Postpartum/physiopathology ; Depression, Postpartum/psychology ; Female ; Humans ; Infant, Newborn ; Male ; Neonatal Abstinence Syndrome/epidemiology ; Neonatal Abstinence Syndrome/physiopathology ; Pregnancy ; Severity of Illness Index ; West Virginia/epidemiology
Language	English
Publishing date	2018-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197618-7
ISSN	1873-6327 ; 0306-4603
ISSN (online)	1873-6327
ISSN	0306-4603
DOI	10.1016/j.addbeh.2018.09.011
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Article: Angiogenic activity of nicotinic acetylcholine receptors: implications in tobacco-related vascular diseases.

Egleton, Richard D / Brown, Kathleen C / Dasgupta, Piyali

Pharmacology & therapeutics

2008 Volume 121, Issue 2, Page(s) 205–223

Abstract: Cigarette smoking bears a strong etiological association with many neovascularization-related diseases like cancer, cardiovascular disease and macular degeneration. Although cigarette smoke is a complex mixture of many compounds, nicotine is the major ... ...

Abstract	Cigarette smoking bears a strong etiological association with many neovascularization-related diseases like cancer, cardiovascular disease and macular degeneration. Although cigarette smoke is a complex mixture of many compounds, nicotine is the major active and addictive component of tobacco. Recent studies have shown that nicotine can enhance angiogenesis and arteriogenesis in several experimental systems and animal models. The pro-angiogenic activity of nicotine is mediated by nicotinic acetylcholine receptors, which have been found to be expressed on several types of cells in the vasculature like endothelial cells, smooth muscle cells and immune cells. The present review summarizes the pro-angiogenic activity of nicotine in neoplastic and non-neoplastic disease. The present article focuses on the role of nAChRs, particularly alpha7-nAChR in mediating the pro-angiogenic effects of nicotine. The expression patterns of nAChRs on various components of the vasculature are discussed. The complex signaling pathways underlying the angiogenic effect of nAChRs are described. The review also takes a look at the therapeutic potential of nAChR agonists and antagonists in angiogenesis-related diseases. More basic research as well as patient-oriented clinical studies is needed to firmly establish the clinical potential of nAChR ligands in angiogenesis-based therapies. Also the side effects of targeting nAChRs remain to be established in patients. The development of selective nAChR agonists and antagonists with improved specificity may represent novel therapeutic regimens in the treatment of angiogenesis-related diseases.
MeSH term(s)	Animals ; Humans ; Neoplasms/chemically induced ; Neoplasms/drug therapy ; Neoplasms/physiopathology ; Neovascularization, Pathologic/chemically induced ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/physiopathology ; Nicotine/toxicity ; Nicotinic Agonists/pharmacology ; Nicotinic Agonists/toxicity ; Nicotinic Antagonists/pharmacology ; Receptors, Nicotinic/drug effects ; Receptors, Nicotinic/metabolism ; Signal Transduction/drug effects ; Smoking/adverse effects ; Nicotiana/chemistry ; Nicotiana/toxicity
Chemical Substances	Nicotinic Agonists ; Nicotinic Antagonists ; Receptors, Nicotinic ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2008-11-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2008.10.007
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Zs.A 1183: Show issues

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Article: Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis.

Egleton, Richard D / Brown, Kathleen C / Dasgupta, Piyali

Trends in pharmacological sciences

2008 Volume 29, Issue 3, Page(s) 151–158

Abstract: Nicotinic acetylcholine receptors (nAChRs) constitute a heterogeneous family of ion channels that mediate fast synaptic transmission in neurons. They have also been found on non-neuronal cells such as bronchial epithelium and keratinocytes, underscoring ... ...

Abstract	Nicotinic acetylcholine receptors (nAChRs) constitute a heterogeneous family of ion channels that mediate fast synaptic transmission in neurons. They have also been found on non-neuronal cells such as bronchial epithelium and keratinocytes, underscoring the idea that they have functions well beyond neurotransmission. Components of cigarette smoke, including nicotine and NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone], are agonists of nAChRs. Given the association of tobacco use with several diseases, the non-neuronal nAChR signaling pathway has considerable implications for cancer and cardiovascular disease. Recent studies have shown that alpha7 is the main nAChR subunit that mediates the proliferative effects of nicotine in cancer cells. As a result, alpha7 nAChR might be a valuable molecular target for therapy of cancers such as lung cancer and mesothelioma. Future studies involving the design of nAChR antagonists with improved selectivity might identify novel strategies for the treatment of tobacco-related cancers. Here we review the cellular roles of non-neuronal nAChRs, including regulation of cell proliferation, angiogenesis, apoptosis, migration, invasion and secretion.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Humans ; Neoplasms/blood supply ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Neovascularization, Pathologic/chemically induced ; Neovascularization, Pathologic/metabolism ; Nicotine/toxicity ; Nitrosamines/toxicity ; Receptors, Nicotinic/biosynthesis ; Receptors, Nicotinic/metabolism ; Signal Transduction/drug effects ; Nicotiana/adverse effects ; Nicotiana/chemistry
Chemical Substances	Nitrosamines ; Receptors, Nicotinic ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2008-02-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2007.12.006
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Zs.MG 6: Show issues

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