Molecular basis of restenosis and potential therapeutic targets

2005 ◽  
pp. 39-45 ◽  
Author(s):  
Yiming Yang ◽  
Andrew Marks ◽  
Steven Marx
Keyword(s):  
Molecular Basis ◽  
Therapeutic Targets

Defect in DNA Double Strand Break Response in Paediatric ALL Is Caused by Upregulation of Multiple Pro-Survival Pathways That Can Serve as Therapeutic Targets.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3344-3344
Author(s):  
Tatjana Stankovic ◽  
Eliot Marston ◽  
Victoria Weston ◽  
Angelo Agathanggelou ◽  
Katie Mapp ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Molecular Basis ◽  
Functional Module ◽  
Therapeutic Targets ◽  
Gene Set Enrichment Analysis ◽  
Dna Damaging Agents ◽  
Survival Pathways ◽  
Dna Dsbs ◽  
Differential Phosphorylation

Abstract The molecular basis of clinical heterogeneity in paediatric ALL is poorly understood. Defects in cellular responses to DNA double strand breaks (DSBs) have been associated with resistance to DNA damaging agents and poor clinical response in patients with leukaemia. We have previously shown that one third of paediatric ALL tumours exhibit in vitro defect in ionising radiation (IR)-induced apoptosis, despite retained integrity of p53 pathway. In this study we addressed molecular basis of defective (DSB) response in paediatric ALL with the view of identifying novel therapeutic targets. We analysed differences in transcriptional and posttranscriptional in vitro responses to IR in 22 ALL patients, stratified as either apoptotic resistant or apoptosis sensitive. Analysis of coordinate IR induced expression of functionally related genes, by two independent methods (gene set enrichment analysis, GSEA, and functional module analysis) revealed in resistant cases differential upregulation of multiple pro-survival pathways involved in EGF, PDGF, IGF, PI3 and MAPK signalling. In response to IR resistant ALLs also showed differentially induced phosphorylation of Akt and S6, downstream targets in PI-3 pathway. Array analysis of 42 receptor tyrosine kinases (TRKs), revealed differential phosphorylation of TRKs that act upstream of the PI3 including ErbB3,4, FGF R4,2a, VEGF R1,2 as well as IGF-I R. Furthermore, we were able to demonstrate that in apoptotic resistant leukaemias PI3/Akt upregulation during IR response lead to differential phosphorylation of DNA-PK catalytic subunit, a protein involved in non homologous end joining (NHEJ) repair of DNA DSBs. Consequently, increased repair of DSBs was observed in apoptosis resistant ALL cases and this was documented by faster resolution of IR induced intranuclear foci of γH2AX, a marker of DNA DSBs. Finally, pharmacological inhibition of pro-survival pathways PI3-Akt, IGF and MAPK in resistant leukaemias restored sensitivity to IR. We suggest that abnormal activation of pro-survival pathways during DSB response may represent one of the mechanisms of resistance to DNA damaging agents in paediatric ALLs and that targeting these pathways should be considered as therapeutic approach in aggressive form of disease.

scholarly journals Molecular basis of applying antimutagens as anticarcinogens

2005 ◽  
Vol 3 (3) ◽  
pp. 19-32 ◽  
Author(s):  
Roza I Goncharova ◽  
Tatyana D Kuzhir
Keyword(s):  
Molecular Basis ◽  
Therapeutic Targets ◽  
Molecular Targets ◽  
Current Data ◽  
Experimental Results ◽  
Molecular Processes ◽  
Dihydropyridine Derivatives ◽  
Natural And Synthetic

The paper presents a review of current data on mechanisms of natural and synthetic antimutagen action underlying the expediency and availability of their application as anticarcinogens. Previously, some molecular processes involved in carcinogenesis as well as some therapeutic targets are considered. The effects of antimutagens on those or other molecular targets have been summarized in table. Along with the literature data on plant antimutagens, some experimental results and supposed mechanisms of the 1,4-dihydropyridine derivatives have been analyzed.

AML1/RUNX1 functions as a cytoplasmic attenuator of NF-κB signaling in the repression of myeloid tumors

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6626-6637 ◽  
Author(s):  
Masahiro Nakagawa ◽  
Munetake Shimabe ◽  
Naoko Watanabe-Okochi ◽  
Shunya Arai ◽  
Akihide Yoshimi ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Growth And Development ◽  
Chromosomal Abnormalities ◽  
Hematopoietic Cells ◽  
Therapeutic Targets ◽  
Hematologic Malignancies ◽  
Leukemic Cells ◽  
Human Leukemia ◽  
Iκb Kinase

Abstract Functional deregulation of transcription factors has been found in many types of tumors. Transcription factor AML1/RUNX1 is one of the most frequent targets of chromosomal abnormalities in human leukemia and altered function of AML1 is closely associated with malignant transformation of hematopoietic cells. However, the molecular basis and therapeutic targets of AML1-related leukemia are still elusive. Here, we explored immediate target pathways of AML1 by in vitro synchronous inactivation in hematopoietic cells. We found that AML1 inhibits NF-κB signaling through interaction with IκB kinase complex in the cytoplasm. Remarkably, AML1 mutants found in myeloid tumors lack the ability to inhibit NF-κB signaling, and human cases with AML1-related leukemia exhibits distinctly activated NF-κB signaling. Furthermore, inhibition of NF-κB signaling in leukemic cells with mutated AML1 efficiently blocks their growth and development of leukemia. These findings reveal a novel role for AML1 as a cytoplasmic attenuator of NF-κB signaling and indicate that NF-κB signaling is one of the promising therapeutic targets of hematologic malignancies with AML1 abnormality.

Structural and Molecular Basis of Carbohydrate-Protein Interaction Systems as Potential Therapeutic Targets

2011 ◽  
Vol 17 (17) ◽  
pp. 1672-1684 ◽  
Author(s):  
Yukiko Kamiya ◽  
Maho Yagi-Utsumi ◽  
Hirokazu Yagi ◽  
Koichi Kato
Keyword(s):  
Protein Interaction ◽  
Molecular Basis ◽  
Therapeutic Targets

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

1974 ◽  
Vol 32 ◽  
pp. 208-209
Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier
Keyword(s):  
Excited State ◽  
Ground State ◽  
Molecular Basis ◽  
Light Emission ◽  
Chemical Basis ◽  
Electronic Excited State ◽  
Colonial Form ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

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