Targeted Chemotherapy in Drug-Resistant Tumors, Noninvasive Imaging of P-Glycoprotein-Mediated Functional Transport in Cancer, and Emerging Role of Pgp in Neurodegenerative Diseases

2009 ◽  
pp. 141-181 ◽  
Author(s):  
Jothilingam Sivapackiam ◽  
Seth T. Gammon ◽  
Scott E. Harpstrite ◽  
Vijay Sharma
Keyword(s):  
Neurodegenerative Diseases ◽  
Noninvasive Imaging ◽  
Targeted Chemotherapy ◽  
Drug Resistant ◽  
P Glycoprotein

Potential Role of Dual NF-κB and Oxidative Stress Pathway Inhibitor, OT-304 as a Novel Drug Resistance-Reversing Agent.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4211-4211
Author(s):  
Shaker A. Mousa ◽  
Ghanshyam Patil ◽  
Abdelhadi Rebbaa
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Tumor Cells ◽  
Genetic Alterations ◽  
Potential Candidate ◽  
Drug Resistant ◽  
P Glycoprotein ◽  
And Oxidative Stress

Abstract The development of resistance to chemotherapy represents an adaptive biological response by tumor cells that leads to treatment failure and patient relapse. During the course of their evolution (intrinsic resistance) or in response to chemotherapy (acquired resistance), tumor cells may undergo genetic alterations to possess a drug resistant phenotype. Dysregulation of membrane transport proteins and cellular enzymes, as well as altered susceptibility to commit to apoptosis are among the mechanisms that contribute to the genesis of acquired drug resistance. Recently, the development of approaches to prevent and/or to reverse this phenomenon has attracted special interest and a number of drug candidates have been identified. Despite strong effects observed for these candidates in vitro, however, most of them fail in vivo. In the present study, we have identified a novel small molecule inhibitor of dual NF-κB and oxidative stress pathways, OT-304, as a potential candidate to reverse drug resistance. Initial investigations indicate that this compound effectively inhibits proliferation of doxorubicin-sensitive and doxorubicin-resistant cells to the same extent, suggesting that it is capable of bypassing the development of drug resistance. Additional experiments reveal that OT-304 enhances cancer cell sensitivity to doxorubicin and to etoposide, particularly in cells characterized by the over-expression of the drug transporter P-glycoprotein. These findings suggest that either the expression/and or the function of P-glycoprotein could be affected by OT-304. In vivo studies using tumor xenografts in nude mice showed that OT-304 is also capable of preventing the growth of drug resistant cancer cells. This later finding further confirms the role of OT-304 as a drug resistance-reversing agent and warrants further pre-clinical and clinical investigation to determine its efficacy in treating aggressive tumors.

Role of P-glycoprotein inhibitors in children with drug-resistant epilepsy

2017 ◽  
Vol 136 (6) ◽  
pp. 639-644 ◽  
Author(s):  
H. A. Elkhayat ◽  
R. H. Aly ◽  
I. A. Elagouza ◽  
R. H. El-Kabarity ◽  
Y. I. Galal
Keyword(s):  
Drug Resistant ◽  
P Glycoprotein ◽  
Drug Resistant Epilepsy ◽  
Glycoprotein Inhibitors

Pharmacogenetics of Clozapine: In Vivo Role of Cytochrome P450 Isoforms and P-Glycoprotein

2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap
Keyword(s):  
Cytochrome P450 ◽  
P Glycoprotein ◽  
Cytochrome P450 Isoforms

The neuroendocrinological role of P-glycoprotein

2005 ◽  
Vol 113 (08) ◽  
Author(s):  
M Ebinger ◽  
MB Müller ◽  
M Uhr
Keyword(s):  
P Glycoprotein

Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽  
2020 ◽  
Vol 3 ◽  
Author(s):  
S. A. Sorokina ◽  
◽  
Yu. Yu. Stroilova ◽  
V. I. Muronets ◽  
Z. B. Shifrina ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Characteristics ◽  
Short Review ◽  
External Factors ◽  
Amyloid Aggregation ◽  
Amyloid Proteins ◽  
Molecular Parameters ◽  
Amyloid Aggregates ◽  
Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

2011 ◽  
Vol 256 (3) ◽  
pp. 418-424 ◽  
Author(s):  
Vasilis P. Androutsopoulos ◽  
Konstantinos Kanavouras ◽  
Aristidis M. Tsatsakis
Keyword(s):  
Neurodegenerative Diseases ◽  
Paraoxonase 1
Sign in / Sign up

Export Citation Format

Share Document