Search results for "53"

CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.

2017

ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein mic…

Wip1 phosphatase: between p53 and MAPK kinases pathways.

2016

IF 5.008; International audience; Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical com…

The Role of p53 Signaling in Colorectal Cancer.

2021

Simple Summary The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development. Deactivating p53 signaling either by altering p53 regulators or by p53 mutations occurs frequently in human colorectal carcinoma (CRC). Forty-three percent of CRCs harbor p53 mutations that reduce wild-type p53 tumor suppressor activity and often provide neo-morphic functions, which contribute to tumorigenesis. In this review, we summarize wild-type p53 signaling, how it can be deregulated in CRC, and the functional and phenotypical effects of p53 mutations. We also discuss current therapeutic strategies of targeting p53. Abstract The tra…

Statement complementing the EFSA Scientific Opinion on application (EFSA‐GMO‐DE‐2011‐95) for the placing on the market of genetically modified maize …

2018

Abstract The GMO Panel was previously not in the position to complete the food/feed safety assessment of maize 5307 due to an inadequate 28‐day toxicity study necessary for an appropriate assessment of eCry3.1Ab protein. Following a mandate from the European Commission, the GMO Panel assessed a supplementary 28‐day toxicity study in mice on the eCry3.1Ab protein (1,000 mg/kg body weight (bw) per day) to complement its scientific opinion on application EFSA‐GMO‐DE‐2011‐95 for the placing on the market of the maize 5307 for food and feed uses, import and processing. The supplementary 28‐day toxicity study did not show adverse effects. Taking into account the previous assessment and the new in…

Influence of the drawing process on the defect generation in multistep-index germanium-doped optical fibers

2009

International audience; Variation of germanium lone pair center (GLPC) concentration in germanosilicate multistep-index optical fibers and preforms was studied using confocal microscopy luminescence technique. The experimental results provide evidence that in the central core region ([Ge] ~11 wt. % ) of our specific canonical samples the ratio [GLPC]/[Ge] is five times larger in fiber than in preforms. The relative influence of the glass composition and of the drawing process on the generation efficiency of the GLPC defects that drive the glass photosensitivity is discussed. The radial distribution of these defects suggests a possible enhancement of the defect creation related to the intern…

Rho resonance, timelike pion form factor, and implications for lattice studies of the hadronic vacuum polarization

2020

We study isospin-1 P-wave ππ scattering in lattice QCD with two flavors of O(a) improved Wilson fermions. For pion masses ranging from mπ=265 MeV to mπ=437 MeV, we determine the energy spectrum in the center-of-mass frame and in three moving frames. We obtain the scattering phase shifts using Lüscher’s finite-volume quantization condition. Fitting the dependence of the phase shifts on the scattering momentum to a Breit-Wigner form allows us to determine the corresponding ρ mass mρ and gρππ coupling. By combining the scattering phase shifts with the decay matrix element of the vector current, we calculate the timelike pion form factor, Fπ, and compare the results to the Gounaris-Sakurai repr…

Nitrogen isotopes in tooth enamel record diet and trophic level enrichment: results from a controlled feeding experiment

2021

Nitrogen isotope ratios (δ15N) are a well-established tool for investigating the dietary and trophic behavior of animals in terrestrial and marine food webs. To date, δ15N values in fossils have primarily been measured in collagen extracted from bone or dentin, which is susceptible to degradation and rarely preserved in deep time (>100,000 years). In contrast, tooth enamel organic matter is protected from diagenetic alteration by the mineral structure of hydroxyapatite and thus is often preserved over geological time. However, due to the low nitrogen content (<0.01 %) of enamel, the measurement of its nitrogen isotopic composition has been prevented by the analytical limit…

Dental microwear texture analysis correlations in guinea pigs (Cavia porcellus) and sheep (Ovis aries) suggest that dental microwear texture signal c…

2022

Strontium Uptake and Intra-Population 87Sr/86Sr Variability of Bones and Teeth—Controlled Feeding Experiments With Rodents (Rattus norvegicus, Cavia …

2020

Strontium isotopes in biogenic apatite, especially enamel, are widely employed to determine provenance and track migration in palaeontology and archaeology. Body tissues record the 87Sr/86Sr of bioavailable Sr of ingested food and water. To identify non-local individuals, knowledge of the 87Sr/86Sr of a non-migratory population is required. However, varying factors such as tissue turnover rates, feeding selectivity, Sr content, digestibility of food, and the ingestion of mineral dust can influence body tissue 87Sr/86Sr. To evaluate the Sr contribution of diet and water to mammalian hard tissues 87Sr/86Sr, controlled feeding studies are necessary. Here we present 87Sr/86Sr from controlled fe…

Digestion of bamboo compared to grass and lucerne in a small hindgut fermenting herbivore, the guinea pig (Cavia porcellus)

2022

Bamboo is an enigmatic forage, representing a niche food for pandas and bamboo lemurs. Bamboo might not represent a suitable forage for herbivores relying on fermentative digestion, potentially due to its low fermentability. To test this hypothesis, guinea pigs (n = 36) were used as model species and fed ad libitum with one of three forages (bamboo, lucerne, or timothy grass) in a fresh or dried state, with six individuals per group, for 3 weeks. The nutrient composition and in vitro fermentation profile of bamboo displayed low fermentation potential, i.e. high lignin and silica levels together with a gas production (Hohenheim gas test) at 12 h of only 36% of that of lucerne and grass. Alth…