scholarly journals Proteotoxic Stress Induces a Cell-Cycle Arrest by Stimulating Lon to Degrade the Replication Initiator DnaA

Cell ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 623-636 ◽  
Author(s):  
Kristina Jonas ◽  
Jing Liu ◽  
Peter Chien ◽  
Michael T. Laub
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Proteotoxic Stress ◽  
Cycle Arrest ◽  
A Cell ◽  
Replication Initiator

Exploratory analysis of the effect of taselisib on downstream pathway modulation and correlation with tumor response in ER-positive/HER2-negative early-stage breast cancer from the LORELEI trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1050-1050 ◽  
Author(s):  
Paolo Nuciforo ◽  
Dominik Hlauschek ◽  
Cristina Saura ◽  
Evandro de Azambuja ◽  
Roberta Fasani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Early Stage ◽  
Objective Response ◽  
Wild Type ◽  
Cycle Arrest ◽  
Er Positive ◽  
A Cell ◽  
Tumor Biopsies ◽  
Clinical Trial Information

1050 Background: Taselisib (T) is an oral, potent, selective inhibitor of Class I PI3-kinase with enhanced activity against PIK3CA mutant cancer cells. Results from the LORELEI trial have demonstrated a significant improvement in ORR (objective response rate) by centrally assessed magnetic resonance imaging in all randomized patients as well as in the PIK3CA mutant (MT) cohort treated with neoadjuvant T plus letrozole (L) compared to placebo (P) plus L. Here we present the results of exploratory analyses of selected pathway-related phosphoproteins. Methods: Baseline (BL) and week3 (W3) tumor biopsies were obtained from 334 patients enrolled in the trial. Phosphoproteins (pAKT, pPRAS40 and pS6) were analyzed by IHC. BL levels as well as changes from BL to W3 were correlated with response assessed either by ORR or cell cycle arrest (Ki67 at W3 < 2.7%). Results: In the overall population, BL phosphoproteins levels were similar between the T and P arms. Higher pAKT (p < 0.001) and pPRAS40 (p = 0.004) levels were observed in MT vs wild-type (WT), whereas the opposite result was found for pS6 (p = 0.03). Treatment-induced absolute changes of phosphoproteins adjusted for BL levels were not significantly different between the T and P arms in the overall population, except for pPRAS40 with higher decrease in the T arm (p = 0.014). After stratification for PIK3CA genotype, a significantly greater decrease in expression levels was observed for pPRAS40 (p < 0.001) and pS6 (p = 0.020) in MT tumors treated with T. The treatment effects were not significantly different in the WT population. A trend for an association between decrease in pS6 levels at W3 and improved ORR was observed in the MT (p = 0.08) and T (p = 0.09) subgroups. The magnitude of pS6 suppression at W3 was higher in tumors achieving a cell cycle arrest in the MT/T subgroup (biserial correlation = -0.473). Conclusions: Exploratory analyses of phosphoproteins showed bioactivity of taselisib as indicated by downstream pathway suppression. Translational research aiming to integrate these results with additional exploratory biomarkers data is currently ongoing. Clinical trial information: NCT02273973.

scholarly journals Mitochondrial DNA Damage Initiates a Cell Cycle Arrest by a Chk2-associated Mechanism in Mammalian Cells

2009 ◽  
Vol 284 (52) ◽  
pp. 36191-36201 ◽  
Author(s):  
Christopher A. Koczor ◽  
Inna N. Shokolenko ◽  
Amy K. Boyd ◽  
Shawn P. Balk ◽  
Glenn L. Wilson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Cell Cycle Arrest ◽  
Mammalian Cells ◽  
Mitochondrial Dna Damage ◽  
Cycle Arrest ◽  
A Cell

scholarly journals Telomeres come up short in heart regeneration

2016 ◽  
Vol 213 (5) ◽  
pp. 497-497
Author(s):  
Ben Short
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Heart Regeneration ◽  
Cycle Arrest ◽  
A Cell

Cardiomyocyte telomeres erode after birth, inducing a cell-cycle arrest that limits the heart’s capacity for regeneration.

scholarly journals Agmatine inhibits growth via a cell cycle arrest and confers resistance to apoptosis

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Mary Ann Arndt ◽  
Eva Parisi ◽  
Masato Isome ◽  
Joseph Satriano
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
A Cell

Cell cycle arrest and cellular differentiation mediated by a cell surface sialoglycopeptide

Life Sciences ◽  
1991 ◽  
Vol 48 (19) ◽  
pp. 1813-1820 ◽  
Author(s):  
Gregory D. Edson ◽  
Heideh K. Fattaey ◽  
Terry C. Johnson
Keyword(s):  
Cell Cycle ◽  
Cell Surface ◽  
Cell Cycle Arrest ◽  
Cellular Differentiation ◽  
Cycle Arrest ◽  
A Cell
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