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Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph

Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents has become critical for lung cancer treatment. In this study, compound AS7128 was selected from a 2-million entry chemical library screening and identified as a candidate drug against non-small cell lung cancer in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and, thus, increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs through disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insight for using iASPP as a therapeutic target for non-small cell lung cancer treatment.

A new space-time coding scheme is drawn upon the concepts of concatenation, multilevel coding, and spatial modulation. In light of a space-time block coded spatial modulation scheme, several component codes are combined in conjunction with set partitioning of the transmission matrix set according to the coding gain distance criterion. Then, the associated scheme is further concatenated with an outer Reed-Solomon code. Simulation results show that the proposed scheme is superior as regards its bit error performance.

Cushing response is the reaction of blood pressure, heart rate and respiratory pattern to increased intracranial pressure. We try to recognize this well-known phenomenon in a patient with head injury, using wavelet transform to abolish noises and preserve the true signals.

Background Angiogenesis is a hallmark of cancer and plays a critical role in lung cancer progression, which involves interactions between cancer cells, endothelial cells and the surrounding microenvironment. However, the gene expression profiles and the changes in the biological phenotype of vascular endothelial cells after interactions with lung cancer cells remain unclear. Methods An indirect transwell co-culture system was used to survey the interaction between human umbilical vein endothelial cells (HUVECs) and human lung adenocarcinoma CL1-5 cells, as well as to investigate the morphological and molecular changes of HUVECs. The differentially expressed genes (DEGs) in HUVECs after co-culture with cancer cells were identified by microarray. Moreover, a publicly available microarray dataset of 293 non-small-cell lung cancer (NSCLC) patients was employed to evaluate the prognostic power of the gene signatures derived from HUVECs. Results The interaction between HUVECs and lung cancer cells changes the morphology of HUVECs, causing them to have a mesenchymal-like morphology and alter their cytoskeleton organization. Furthermore, after co-culture with lung cancer cells, HUVECs showed increased cell motility and microvessel tube formation ability and a decreased apoptotic percentage. Transcriptomic profiling of HUVECs revealed that many survival-, apoptosis- and angiogenesis-related genes were differentially expressed after interactions with lung cancer cells. Further investigations showed that the PI3K/Akt signalling pathway and COX-2 are involved in endothelial tube formation under the stimulation of lung cancer cells. Moreover, Rac-1 activation might promote endothelial cell motility through the increased formation of lamellipodia and filopodia. The inhibitors of PI3K and COX-2 could reverse the increased tube formation and induce the apoptosis of HUVECs. In addition, the gene signatures derived from the DEGs in HUVECs could predict overall survival and disease-free survival in NSCLC patients and serve as an independent prognostic factor. Conclusions In this study, we found that cancer cells can promote endothelial cell tube formation and survival, at least in part, through the PI3K/Akt signalling pathway and thus change the microenvironment to benefit tumour growth. The gene signatures from HUVECs are associated with the clinical outcome of NSCLC patients. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0495-3) contains supplementary material, which is available to authorized users.

Titanium dioxide has been recognized as an excellent photocatalyst material applied on many fields especially for environmental science or engineering. However, the effect of acid washing treatment on the morphology or phase and pore structures of titania nanotubes (TNs) has not still been clearly investigated. The variation of morphology, formation mechanism, phase structure, and pore structure of TN were thus characterized with FE-SEM, TEM, XRD, and N2 BET isotherms, respectively in the present work. Titania nanotube synthesized via a simple hydrothermal chemical process formed a crystalline structure with open-ended and multiwall morphologies. The XRD patterns and N2 BET isotherms implied that the acid washing techniques could improve the TN surface area and the pore size distribution up to 292 m2 g−1 and 40–60 nm, respectively. According to EXAFS/XANES spectra, the structure of the TN is closer to the anatase specimen and much more correlated with octahedral structure. Effects of the pore structure variation on basic dye (Basic Green 5 (BG5)) adsorption by TN were discussed in the present work. Moreover, the adsorption ability, mechanisms, and kinetics of BG5 dye onto TN were also examined with the aid of model analyses of the adsorption equilibrium and kinetic data. Therefore, the potential of TN for the removal of BG5 dye contaminant from wastewaters implied that further development would be warranted.

The expressions of different vascular endothelial growth factor (VEGF) isoforms are associated with the degree of tumor invasiveness and the patient's prognosis in human cancers. We hypothesized that different VEGF isoforms can exert different effects on the functional and structural characteristics of tumor angiogenesis. We used dynamic contrast-enhanced MRI (DCE-MRI) and steady-state contrast-enhanced MRI (SSCE-MRI) to evaluate in vivo vascular functions (e.g., perfusion and permeability) and structural characteristics (e.g., vascular size and vessel density) of the tumor angiogenesis induced by different VEGF isoforms (VEGF121, VEGF165, and VEGF189) in a murine xenograft model of human lung cancer. Tumors overexpressing VEGF189 were larger than those overexpressing the other two VEGF isoforms. The K(trans) map obtained from DCE-MRI revealed that the perfusion and permeability functions of tumor microvessels was highest in both the rim and core regions of VEGF189-overexpressing tumors (p

A new taxon belonging to Neopterygians is described, based on very nicely preserved specimens from the rich vertebrate levels recently discovered in Luoping County, Yunnan Province, South China. This new assemblage dates to Pelsonian (Anisian, Middle Triassic), about the same age of the Panxian Fauna from the nearby Guizhou Province. The Luoping Fauna, yielding this new taxon, is turning out to be one of the most important fish faunas of the whole Middle Triassic and the oldest evidence of the fish radiation of this time span. This new genus of basal neopterygian shows unique derived characters, especially for the almost naked body, with a single row of urodermals covering the body lobe in the tail and a row of very small and thin scales bearing the lateral line canal along the flank. Also in the axial skeleton the new taxon shows peculiar characters such as the neural spines perfectly aligned to each paired neural arches and abdominal ribs well developed. Concerning skull bones, no suborbitals have been detected., Rivista italiana di Paleontologia e Stratigrafia, Vol 116, No 2

Immunotherapy is often effective only for small tumor burdens and, in many cases, is restricted to subcutaneous tumors. Here, we investigated the antitumor effects of combination therapy with GM-CSF and IL-12 on orthotopic liver tumors with intermediate or large tumor volumes, or on chemically-induced multifocal liver tumors in animals. Adenoviruses encoding GM-CSF or IL-12 were injected intratumorally to animals bearing transplanted tumors, or injected via intrahepatic artery in animals with primary multifocal liver tumors induced by diethylnitrosamine. Our results demonstrated that IL-12, but not GM-CSF, monotherapy displayed significant therapeutic effects, whereas combination therapy with both cytokines displayed synergistic antitumor effects not only on transplanted tumor models with intermediate or large tumor loads, but also on carcinogen-induced multifocal liver tumors. Effector cell analyses, revealed by in vivo cell subset depletion, flow cytometry analysis, and immunohistochemical staining of tumor infiltrates, indicated that NK cells were the prominent antitumor effectors for the IL-12–mediated antitumor activity, whereas CD8+ T cells, NKT cells, and macrophages were more important than NK cells in the combination therapy–mediated antitumor effects. Both IL-12 monotherapy and combination therapy could induce various types of effectors and high levels of IFN-γ; however, the latter induced much higher levels than the former, which may explain why combination therapy is superior to IL-12 monotherapy. Conclusion: Combination therapy with GM-CSF and IL-12 represents a promising immunotherapy strategy for treating orthotopic, widespread liver tumors. (HEPATOLOGY 2007;45:746–754.)

SummaryViruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.