Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.     

Neurite outgrowth is enhanced by laminin-mediated down-regulation of the low affinity neurotrophin receptor, p75NTR

Laminin (LN), an extracellular matrix component, is a key factor in promoting axonal regeneration, coordinately regulating growth in conjunction with trophic signals provided by the neurotrophins, including nerve growth factor (NGF). This study investigated potential interactions between the LN and NGF-mediated signaling pathways in PC12 cells and primary neurons. Neurite outgrowth stimulated by NGF was enhanced on a LN substrate. Western blot analysis of pertinent signal transduction components revealed both enhanced phosphorylation of early signaling intermediates upon co-stimulation, and a LN-induced down-regulation of p75NTR which could be prevented by the addition of integrin inhibitory arginine-glycine-aspartate (RGD) peptides. This p75NTR down-regulation was associated with a LN-mediated up-regulation of PTEN and resulted in a decrease in Rho activity. Studies using over-expression or siRNA-mediated knock-down of PTEN demonstrate a consistent inverse relationship with p75NTR, and the over-expression of p75NTR impaired neurite outgrowth on a LN substrate, as well as resulting in sustained activation of Rho which is inhibitory to neurite outgrowth. p75NTR is documented for its role in the transduction of inhibitory myelin-derived signals, and our results point to extracellular matrix regulation of p75NTR as a potential mechanism to ameliorate inhibitory signaling leading to optimized neurite outgrowth.     

Biomarker of food intake for assessing the consumption of dairy and egg products

Dairy and egg products constitute an important part of Western diets as they represent an excellent source of high-quality proteins, vitamins, minerals and fats. Dairy and egg products are highly diverse and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of these foods and health outcomes, it is important to identify reliable biomarkers of their intake. Biomarkers of food intake (BFIs) provide an accurate measure of intake, which is independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for dairy products and BFIs for egg products commonly consumed in Europe. Strikingly, only a limited number of compounds have been reported as markers for the intake of these products and none of them have been sufficiently validated. A series of challenges hinders the identification and validation of BFI for dairy and egg products, in particular, the heterogeneous composition of these foods and the lack of specificity of the markers identified so far. Further studies are, therefore, necessary to validate these compounds and to discover new candidate BFIs. Untargeted metabolomic strategies may allow the identification of novel biomarkers, which, when taken separately or in combination, could be used to assess the intake of dairy and egg products.     

Shear wave induced resonance elastography of soft heterogeneous media

In the context of ultrasound dynamic elastography imaging and characterization of venous thrombosis, we propose a method to induce mechanical resonance of confined soft heterogeneities embedded in homogenous media. Resonances are produced by the interaction of horizontally polarized shear (SH) waves with the mechanical heterogeneity. Due to such resonance phenomenon, which amplifies displacements up to 10 times compared to non-resonant condition, displacement images of the underlying structures are greatly contrasted allowing direct segmentation of the heterogeneity and a more precise measurement of displacements since the signal-to-noise ratio is enhanced. Coupled to an analytical model of wave scattering, the feasibility of shear wave induced resonance (SWIR) elastography to characterize the viscoelasticity of a mimicked venous thrombosis is demonstrated (with a maximum variability of 3% and 11% for elasticity and viscosity, respectively). More generally, the proposed method has the potential to characterize the viscoelastic properties of a variety of soft biological and industrial materials.     

Density dependence of Anaphes sordidatus (Hymenoptera: Mymaridae) parasitism on eggs of Listronotus oregonensis (Coleoptera: Curculionidae)

Listronotus oregonensis (LeConte) (Coleoptera: Curculionidae) oviposits in carrot leaves and the larvae feed in carrot roots. Its eggs are parasitized by Anaphes sordidatus (Girault) (Hymenoptera: Mymaridae) throughout its oviposition period. This parasitoid is the major biotic mortality factor for L. oregonensis. Parasitism by A. sordidatus was studied for three years in sequentially sown plots of carrots, Daucus carota var. sativa. Over the scason, significantly fewer L. oregonensis eggs were oviposited in later sown carrots than in earlier sown carrots because oviposition started later in late sown plots of carrots. A positive temporal density-dependent relationship was observed each year between parasitism rates and host densities. This positive density dependence occurred in early and mid-summer for earlysown carrots where host density reached 1–2 host eggs per plant but disappeared in late summer when host density decreased while parasitism remained high. Latesown carrots had low host egg density (0.2 host egg per plant) and contributed little to the total number of eggs. In these late sown plots, parasitism increased rapidly to over 80% but no density dependence was observed. Spatially, few statistically significant regressions were found but all indicated a positive spatial density-dependence. Most non-significant regressions occurred because the range of egg density was too small between plots for a given date.     

The helical content of the YscP molecular ruler determines the length of the Yersinia injectisome

The length of the Yersinia injectisome needle is determined by the protein YscP, which could act as a molecular ruler. The analysis of the correlation between the size of YscP and the needle length in seven wild-type strains of Yersinia enterocolitica reinforced this hypothesis but hinted that the secondary structure of YscP might influence needle length. Hence, 11 variants of YscP₅₁₅ were generated by multiple Pro or Gly substitutions. The needle length changed in inverse function of the helical content, indicating that not only the number of residues but also their structure controls length. Taking the secondary motifs into account, Pro/Gly-variants were subjected to in silico modelling to simulate the extension of YscP upon needle growth. The calculated lengths when the helical content is preserved correlated strikingly with the measured needle length, with a constant difference of ∼29 nm, which corresponds approximately to the size of the basal body. These data support the ruler model and show that the functional ruler has a helical structure.     

The carotenoids of a black variety of the larva of the moth, Manduca sexta

The black mutant larva of Manduca sexta contains approximately the same quantity of carotenoids as the normal green type, but there is possibly a slight qualitative difference between them, the former storing more β-carotene and less violaxanthin.     

The P2X7 receptor antagonist JNJ-47965567 administered thrice weekly from disease onset does not alter progression of amyotrophic lateral sclerosis in SOD1G93A mice

Purinergic Signalling - The ATP-gated P2X7 ion channel has emerging roles in amyotrophic lateral sclerosis (ALS) progression. Pharmacological blockade of P2X7 with Brilliant Blue G can ameliorate...