scholarly journals Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models

2015 ◽  
Vol 6 ◽  
Author(s):  
S. Lindsey Davis ◽  
Kelli M. Robertson ◽  
Todd M. Pitts ◽  
John J. Tentler ◽  
Erica L. Bradshaw-Pierce ◽  
...  
2014 ◽  
Vol 50 ◽  
pp. 127-128
Author(s):  
Y. Nakatsuru ◽  
A. Hashimoto ◽  
H. Sootome ◽  
K. Ito ◽  
M. Sakuragi ◽  
...  

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.C Van 't Klooster ◽  
P.M Ridker ◽  
N.R Cook ◽  
J.G.J.V Aerts ◽  
J Westerink ◽  
...  

Abstract Background As treatment for cardiovascular disease (CVD) has improved substantially over the last decades, more patients survive acute CVD manifestations and are at risk for developing cancer as well as recurrent CVD. Due to similar risk factors, including smoking and obesity, patients with established CVD are at higher risk for cancer. Objectives The aim of this study was to develop and externally validate prediction models for the estimation of 10-year and lifetime risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART prospective cohort study (N=7,280) were used for model development, and data from the CANTOS trial (N=9,322) were used for model validation. Predictors were selected based on previously published cancer risk prediction models or cancer risk factors, easy clinical availability, and availability in the derivation dataset (UCC-SMART cohort). A Fine and Gray competing risk-adjusted lifetime model was developed for total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking status, weight, height, alcohol use, antiplatelet use, diabetes mellitus, and C-reactive protein. External calibration for 4-year risks of the total cancer, colorectal cancer, and lung cancer models was good (Figure 1), and C-statistics were 0.63–0.74 in the CANTOS trial population. Median predicted lifetime risks in CANTOS were 26% (range 1%-52%) for total cancer, 4% (range 0%-13%) for colorectal cancer, and 5% (range 0%-37%) for lung cancer. Conclusions Lifetime and 10-year risk of cancer can be estimated with easy to measure variables in patients with established CVD, showing a wide distribution of predicted lifetime risks for total cancer and lung cancer. Using these lifetime models in clinical practice could increase understanding of cancer risk and aid in emphasizing healthy lifestyle changes. Figure 1. Calibration plots of cancer models Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center; Additional funding: CANTOS trial was funded by Novartis Pharmaceuticals.


BioMetals ◽  
2021 ◽  
Author(s):  
Alessio Menconi ◽  
Tiziano Marzo ◽  
Lara Massai ◽  
Alessandro Pratesi ◽  
Mirko Severi ◽  
...  

AbstractChloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2379
Author(s):  
Masaru Terasaki ◽  
Atsuhito Kubota ◽  
Hiroyuki Kojima ◽  
Hayato Maeda ◽  
Kazuo Miyashita ◽  
...  

Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.


2016 ◽  
Vol 344 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Chien-Yu Kao ◽  
Yu-Fen Chung ◽  
Don-Ching Lee ◽  
Jen-Wei Liu ◽  
...  

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