Treatment Strategies in Colorectal Cancer

Colorectal cancer is known to be one of the most commonly diagnosed cancers worldwide. It maintains a high mortality rate despite the newest methodological therapeutic approaches adopted in various academic establishments. The treatment modalities in colorectal cancer follow the degree of disease progression based on staging information. Earliest the cancer is diagnosed, the highest the possibility to be cured. Different strategies are being involved in treating colorectal cancer, starting from simple endoscopic polypectomy to remove a potential malignant polyp, to wider surgical intervention to get rid of a primary unmetastasized tumor, to other concomitant radio-chemotherapy combinations to reduce a bulky tumor rendering it operable, ending in more sophisticated chemotherapeutical regimens combined with targeted drugs to shrink the metastatic lesions and prolong survival rate. Different new treatments are being investigated with a sole aim to preserve the patient’s quality of life and extend life span

Hepatoprotective, Antioxidant, and Anticancer Effects of the Tragopogon porrifolius

Tragopogon porrifolius (Asteraceae), commonly referred to as white salsify, is an edible herb used in Lebanese folk medicine to treat cancer and liver dysfunction. In this study, we investigated the antioxidant activity of Tragopogon porrifolius methanolic extract, both in vitro and in vivo, in addition to its hepatoprotective and anticancer activities. Total phenolic and flavonoid contents were measured and found to be  mg GAE/g and  mg QE/g dry weight, respectively. In vitro antioxidant assays revealed an FRAP value of  µmol Fe2+/g of extract and DPPH IC50 value 15.2 µg/mL. In rats subjected to CCl4-induced hepatotoxicity, significant increase in CAT, SOD, and GST levels was detected. The highest dose of the extract (250 mg/kg) recorded a fold increase of 1.68 for SOD, 2.49 for GST, and 3.2 for CAT. The extract also showed substantial decrease in AST (57%), ALT (56%), and LDH (65%) levels. Additionally, the extract caused a dose-dependent decrease in cell viability and proliferation. In conclusion, the methanolic extract of T. porrifolius displayed a relatively high antioxidant activity both in vitro and in vivo as well as hepatoprotective potential against liver toxicity in rats and anticancer effect on MDA-MB-231 and Caco-2 cells.PublishedN/

Le capital humain en psychologie et la performance des employés

Management and psychology are two disciplines that can't be separated, managing teams requires minimum understanding of their behavior, and personalities to master how to deal with them and lead them and be at their disposal for help or issue solving, the comprehension of employees needs allows companies to work in harmony and exercise its activity effectively. The use of psychometrics facilitates the human resources managers’ tasks, especially when it comes to recruiting. Through the results of those tests, a manager can judge whether an element will fit in the organization and understand its culture and be productive. however, organizations are suggested to engage the employees' creativity and experience to keep up with the fast-paced organizational changes, managers might play the role of coaches that identify the employees' knowledge, expertise, well-being, and happiness, and readiness to change.Management and psychology are two disciplines that can't be separated, managing teams requires minimum understanding of their behavior, and personalities to master how to deal with them and lead them and be at their disposal for help or issue solving, the comprehension of employees needs allows companies to work in harmony and exercise its activity effectively. The use of psychometrics facilitates the human resources managers’ tasks, especially when it comes to recruiting. Through the results of those tests, a manager can judge whether an element will fit in the organization and understand its culture and be productive. however, organizations are suggested to engage the employees' creativity and experience to keep up with the fast-paced organizational changes, managers might play the role of coaches that identify the employees' knowledge, expertise, well-being, and happiness, and readiness to change

IL-1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells.

BACKGROUND: In inflammatory bowel disease (IBD), cytokine levels (such as interleukin-1 (IL-1)) are elevated. We have shown previously that IL-1 activates phospholipid signaling pathways in intestinal epithelial cells (EEC), leading to increased ceramide levels. AIM: To determine whether ceramide induces apoptosis in IEC. METHODS: Apoptosis was evaluated by annexin-V binding or Hoechst nuclear staining. Levels of bcl-2, bcl-x, bax, p53 and p21 were determined by Western blotting, and celi cycle analysis was determined by flow cytometry. RESULTS: IL-1 increased ceramide accumulation in a time-dependent and concentration-dependent manner with a peak response at 4 h, with [IL-1] = 30 ng/ml. Neither IL-1 nor ceramide induced apoptosis in EEC, but they increased bcl-2 levels and decreased bax and p21 levels without affecting bcl-x and p53 levels. They also caused a slight but significant increase in the G2/M phase. These data suggest a role for ceramide in IBD and suggest a possible mechanism for the enhanced tumorigenic activity in IBD patients

Using spatial outliers detection to assess balancing mechanisms in bike sharing systems

International audienceSpatial outliers are objects having a behavior significantly different from their spatial neighbors, in a context where neighbors are heavily correlated. Moran scatterplot is a well-known method that exploits similarity between neighbors in order to detect spatial outliers. In this paper, we proposed first an improved version of Moran scatterplot, using a robust distance metric called Gower's similarity. We used the new version of Moran scatterplot to study the homogeneity of the Parisian bike sharing system (Velib). We carried out different experiments on a real dataset issued from the Velib system. We identified many spatial outliers stations, very different from their neighboring stations (often with much more available bikes or with much more empty docks during the day). Then, we designed and tested a new method that globally improves the distribution of the resources (bikes and docks) among bike stations. This method is motivated by the existence of spatial outliers stations. It relies on a local small change in users behaviors, by adapting their trips to resources' availability around their departure and arrival stations. Results show that, even with a partial users collaboration, the proposed method enhances significantly the global homogeneity of the bike sharing system and therefore the users' satisfaction

The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Forster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process. (C) 2013 Elsevier Inc All rights reserved

WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells

We examined the role of the actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion in response to epidermal growth factor (EGF), a key regulator in carcinoma cell invasion. We found that WAVE2 knockdown (KD) suppresses lamellipod formation and increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous KD of both proteins results in the formation of large jagged protrusions with lamellar properties and increased filopod formation. This suggests that another actin nucleation activity is at work in carcinoma cells in response to EGF. A mammalian Diaphanous–related formin, mDia1, localizes at the jagged protrusions in double KD cells. Constitutively active mDia1 recapitulated the phenotype, whereas inhibition of mDia1 blocked the formation of these protrusions. Increased RhoA activity, which stimulates mDia1 nucleation, was observed in the N-WASP/WAVE2 KD cells and was shown to be required for the N-WASP/WAVE2 KD phenotype. These data show that coordinate regulation between the WASP family and mDia proteins controls the balance between lamellar and lamellipodial protrusion activity

Cofilin determines the migration behavior and turning frequency of metastatic cancer cells

We have investigated the effects of inhibiting the expression of cofilin to understand its role in protrusion dynamics in metastatic tumor cells, in particular. We show that the suppression of cofilin expression in MTLn3 cells (an apolar randomly moving amoeboid metastatic tumor cell) caused them to extend protrusions from only one pole, elongate, and move rectilinearly. This remarkable transformation was correlated with slower extension of fewer, more stable lamellipodia leading to a reduced turning frequency. Hence, the loss of cofilin caused an amoeboid tumor cell to assume a mesenchymal-type mode of movement. These phenotypes were correlated with the loss of uniform chemotactic sensitivity of the cell surface to EGF stimulation, demonstrating that to chemotax efficiently, a cell must be able to respond to chemotactic stimulation at any region on its surface. The changes in cell shape, directional migration, and turning frequency were related to the re-localization of Arp2/3 complex to one pole of the cell upon suppression of cofilin expression