In the tumor microenvironment, chemokine system has a critical role in tumorigenesis and metastasis. The acquisition of stem-like properties by cancer cells is involved in metastasis and drug resistance, which are pivotal problems that result in poor outcomes in patients with lung cancer. Patients with advanced lung cancer present high plasma levels of transforming growth factor-β1 (TGFβ1), which correlate with poor prognostic features. Therefore, TGFβ1 may be important in the tumor microenvironment, where chemokines are widely expressed. However, the role of chemokines in TGFβ1-induced tumor progression still remains unclear. In our study, TGFβ1 upregulated CXC chemokine receptor expression, migration, invasion, epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was the most upregulated chemokine receptor induced by TGFβ1. CXCR7 knockdown resulted in reduction of migration, invasion and EMT induced by TGFβ1, whereas CXCR4 knockdown did not reverse TGFβ1-promoted EMT. CXCR7 silencing significantly decreased cancer sphere-forming capacity, stem-like properties, chemoresistance and TGFβ1-induced CSC tumor initiation in vivo. In clinical samples, high TGFβ1 and CXCR7 expression was significantly associated with the late stages of lung adenocarcinoma. Moreover, TGFβ1 and CXCR7 coexpression was positively correlated with the CSC marker, CD44, which is associated with lymph node metastasis. Besides, patients with high expression of both CXCR7 and TGFβ1 presented a significantly worse survival rate. These results suggest that the TGFβ1-CXCR7 axis may be a prognostic marker and may provide novel targets for combinational therapies to be used in the treatment of advanced lung cancer in the future.

The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via down-regulation of NF-kappaB.

In recent papers (2, 3) it has been shown that the energies of dissociation of simple and complex oxides into the gaseous ions of their component elements are approximately additive, conforming to the relationship where Ei is the "ionic dissociation energy" of the compound (or glass) M,M:,Ml,, . . * 0, and zy is a constant characteristic of element M. This constant may be thought of as the average contribution of one gram-atom of element M to the total energy of dissociation into gaseous ions of compounds or glasses in which each M atom is surrounded by a shell of oxygen atoms. No assumption regarding the nature of the forces (ionic or covalent) holding the M atoms to these oxygens is involved. Differences in the number of oxygens around each M in different compounds or glasses produce departures from strict additivity, but the deviations are not great. A large part of the magnitude of each % value can be attributed to the energies of formation of the gaseous ions, ill+" and 0-?, from the uncharged gaseous atoms, M and 0. In studying other factors affecting the magnitudes of the energy constants, it is of interest to subtract the contributions of these atomic ionization energies-in other words, to compute and compare energy constants,4, for dissociation into gaseous uncharged atoms, rather than ions.The 4 values are related to the % values by the following equation:Here u is the valence of the atom M in the compounds or glasses being considered and Qf designates the heat of formation, obtainable from Bichowsky and Rossini's valuable tabulation (1). Table 1 lists values of e& together with the values of eM from which they were computed by means of equation 2. Some additional €4 values are included, for elements for which the data on ionization energies of the gaseous elements required for the computation of % are not available. The equation used for

Keratinizing epithelium from the hard palate of guinea pigs was used to investigate effects of variations in composition of fixative solutions on tissue preservation. With 2.5% glutaraldehyde as fixative, the volume of the basal intercellular spaces increased significantly when the buffer osmolality was increased by intervals of about 100 mOsm (0.05 M, 0.10 M and 0.15 M). The intercellular space volume appeared to be insensitive to differences in concentration of the fixative within the range of 2.5—5% glutaraldehyde. The preservation of mitochondria was improved by increasing the concentration of glutaraldehyde to 5% or by adding formaldehyde as a second fixative.