Interaction of p53 with the Δ133p53α and Δ160p53α isoforms regulates p53 conformation and transcriptional activity.

The TP53 gene encodes p53, a transcription factor involved in tumor suppression. However, TP53 also encodes other protein isoforms, some of which can disrupt the tumor suppressor functions of p53 even in the absence of TP53 mutations. In particular, elevated levels of the Δ133TP53 mRNA are detected in many cancer types and can be associated with poorer disease-free survival.

Evaluating bank technical efficiency in SADC region.

Efficiency is generally defined as the capacity to deliver desirable results with little effort or input. A bank cannot afford to allocate limited resources at random in a competitive market. Only once the efficiency factors have been identified can resources be allocated in a conscious and effective manner.

Quantification of the pulmonary vascular obstruction index on ventilation/perfusion lung scintigraphy: Comparison of a segmental visual scoring to the Meyer score.

Introduction: Quantifying the pulmonary vascular obstruction index (PVOI) is essential for the management of patients with pulmonary embolism or chronic thromboembolic pulmonary hypertension (CTEPH). The reference method for quantifying the PVOI with planar lung ventilation/perfusion (V/Q) scintigraphy is the Meyer score, which was validated using pulmonary angiography as a reference standard. However, it is complex to use in daily practice.

Adaptation to DNA Damage, an Asymptotic Approach for a Cooperative Non-local System.

Following previous works about integro-differential equations of parabolic type modelling the Darwinian evolution of a population, we study a two-population system in the cooperative case. First, we provide a theoretical study of the limit of rare mutations and we prove that the limit is described by a constrained Hamilton-Jacobi equation. This equation is given by an eigenvalue of a matrix which accounts for the diffusion parameters and the coefficients of the system.

Lung Ventilation/Perfusion Scintigraphy for the Screening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Which Criteria to Use?

Objective: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation.

Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells.

The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies.

Adaptation to DNA damage as a bet-hedging mechanism in a fluctuating environment.

In response to DNA damage, efficient repair is essential for cell survival and genome integrity. In eukaryotes, the DNA damage checkpoint is a signalling pathway that coordinates this response and arrests the cell cycle to provide time for repair. However, when repair fails or when the damage is not repairable, cells can eventually bypass the DNA damage checkpoint and undergo cell division despite persistent damage, a process called adaptation to DNA damage.

p53, A Victim of the Prion Fashion.

Identified in the late 1970s as an oncogene, a driving force leading to tumor development, p53 turned out to be a key tumor suppressor gene. Now p53 is considered a master gene regulating the transcription of over 3000 target genes and controlling a remarkable number of cellular functions. The elevated prevalence of p53 mutations in human cancers has led to a recurring questioning about the roles of mutant p53 proteins and their functional consequences.

Normal Dual Isotope V/Q SPECT Model for Monte-Carlo Studies.

There is currently no reliable or validated tool to delineate and quantify functional lung volumes with ventilation/perfusion (V/Q) SPECT/CT. The main challenges encountered include the physiological non-uniformity of lung function, such as the anterior-to-posterior gradient on perfusion images, and the lack of ground truth to assess the accuracy of delineation algorithms. In that respect, Monte-Carlo simulations would be an interesting tool.

The atypical RhoU/Wrch1 Rho GTPase controls cell proliferation and apoptosis in the gut epithelium.

Background: The mammalian gut epithelium displays among the highest rates of self-renewal, with a turnover time of less than 5 days. Renewal involves concerted proliferation at the bottom of the crypt, migration and differentiation along the crypt-villus axis and anoïkis/shedding in the luminal epithelium. Renewal is controlled by interplay between signalling pathways, among which canonical and non-canonical Wnt signals play prominent roles.

Carboplatin in combination with weekly Paclitaxel as first-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma unfit to EXTREME schedule.

The standard first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma combines Cisplatin, 5 Fluorouracil and Cetuximab, but many patients aren't eligible. We retrospectively evaluated the efficacy and the tolerability of Carboplatin and Paclitaxel in this indication, mostly in patients unfit to Cisplatin. Paclitaxel (80mg/m2) was administered at day 1, 8 and 15 and Carboplatin area under the curve 5 at day 1, repeated every 28 days, for 6 cycles.

∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling.

∆122p53 mice (a model of ∆133p53 isoform) are tumour-prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed ∆122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence and metastasis.

Correction: The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner.

[This corrects the article DOI: 10.1371/journal.pone.

The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner.

The TP53 gene plays essential roles in cancer. Conventionally, wild type (WT) p53 is thought to prevent cancer development and metastasis formation, while mutant p53 has transforming abilities. However, clinical studies failed to establish p53 mutation status as an unequivocal predictive or prognostic factor of cancer progression.

Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells.

Soft tissue sarcomas with complex genomics are very heterogeneous tumors lacking simple prognosis markers or targeted therapies. Overexpression of a subset of mitotic genes from a signature called CINSARC is of bad prognosis, but the significance of this signature remains elusive. Here we precisely measure the cell cycle and mitosis duration of sarcoma cell lines and we found that the mitotic gene products overexpression does not reflect variation in the time spent during mitosis or G2/M.

drives invasion through expression of its Δ133p53β variant.

is conventionally thought to prevent cancer formation and progression to metastasis, while mutant has transforming activities. However, in the clinic, mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of mutation status.

The p53 isoform Δ133p53β promotes cancer stem cell potential.

Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expression of the key pluripotency factors SOX2, OCT3/4, and NANOG.

Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling.

Scope: The aim was to investigate the effect of postprandial triglyceride-rich lipoproteins (TRLs) with different fatty acid compositions on human coronary artery smooth muscle cell (hCASMC) invasion and to identify the molecular pathways involved.

Methods And Results: TRLs were isolated from the plasma of healthy volunteers after the ingestion of single meals enriched in MUFAs, saturated fatty acids (SFAs), or PUFAs. hCASMC invasion was analyzed using transwell chambers with Matrigel.

Eroded human telomeres are more prone to remain uncapped and to trigger a G2 checkpoint response.

Telomeres cap the ends of chromosomes and regulate the replicative life span of human somatic cells. Telomere function is lost upon critical shortening and a p53-dependent checkpoint that detects altered telomere states at the G1/S transition was proposed to act as a regulator of the telomere damage response. We show that telomerase-negative human fibroblasts spend more time in G2 phase as they approach senescence and this delay is associated with manifestations of telomere dysfunction and the triggering of an ATM/ATR-dependent DNA damage signal.

Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity.

Rho GTPases are key regulators of tumour cell invasion and therefore constitute attractive targets for the design of anticancer agents. Several strategies have been developed to modulate their increased activities during cancer progression. Interestingly, none of these approaches took into account the existence of the well-known antagonistic relationship between RhoA and Rac1.

ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion.

The Krüppel-like zinc finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we showed that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo.