Oncogenic role of EAPII in lung cancer development and its activation of the MAPK–ERK pathway

Cancer progression involves multiple complex and interdependent steps, including progressive proliferation, angiogenesis and metastases. The complexity of these processes requires a comprehensive elucidation of the integrated signaling networks for better understanding. EAPII interacts with multiple cancer-related proteins, but its biological significance in cancer development remains unknown. In this report we identified the elevated level of EAPII protein in non-small-cell lung carcinoma (NSCLC) patients and NSCLC cell lines in culture. The oncogenic role of EAPII in lung cancer development was demonstrated using NSCLC cells with genetic manipulations that influence EAPII expression: EAPII overexpression increases proliferation of NSCLC cells with an accelerated transition of cell cycle and facilitates xenograft tumor growth in vivo; EAPII knockdown results in apoptosis of NSCLC cells and reduces xenograft tumor formation. To further explore the mechanism of EAPII's oncogenic role in lung cancer development and to elucidate the potential signaling pathway(s) that EAPII may impact, we employed antibody array to investigate the alternation of the major signaling pathways in NSCLC cells with altered EAPII level. We found that EAPII overexpression significantly activated Raf1 and ERK1/2, but not c-Jun N-terminal kinase and p38 pathways. Consistently, the protein and mRNA levels of MYC and cyclin D1, which are targets of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK–ERK) pathway, are significantly increased by EAPII overexpression. Taken together, we demonstrated that EAPII is an oncogenic factor and the activation of MAPK–ERK signaling pathway by EAPII may contribute to lung cancer development

Induction of autophagy by spermidine promotes longevity.

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African Baobabs with False Inner Cavities: The Radiocarbon Investigation of the Lebombo Eco Trail Baobab

The article reports the radiocarbon investigation results of the Lebombo Eco Trail tree, a representative African baobab from Mozambique. Several wood samples collected from the large inner cavity and from the outer part of the tree were investigated by AMS radiocarbon dating. According to dating results, the age values of all samples increase from the sampling point with the distance into the wood. For samples collected from the cavity walls, the increase of age values with the distance into the wood (up to a point of maximum age) represents a major anomaly. The only realistic explanation for this anomaly is that such inner cavities are, in fact, natural empty spaces between several fused stems disposed in a ring-shaped structure. We named them false cavities. Several important differences between normal cavities and false cavities are presented. Eventually, we dated other African baobabs with false inner cavities. We found that this new architecture enables baobabs to reach large sizes and old ages. The radiocarbon date of the oldest sample was 1425 ± 24 BP, which corresponds to a calibrated age of 1355 ± 15 yr. The dating results also show that the Lebombo baobab consists of five fused stems, with ages between 900 and 1400 years; these five stems build the complete ring. The ring and the false cavity closed 800–900 years ago. The results also indicate that the stems stopped growing toward the false cavity over the past 500 years.Romanian Ministry of National Education CNCS-UEFISCDI under grant PN-II-ID-PCE-2013-76.http://www.plosone.orghb201

Dissolution Enhancement of a Drug Exhibiting Thermal and Acidic Decomposition Characteristics by Fusion Processing: A Comparative Study of Hot Melt Extrusion and KinetiSol® Dispersing

In this study, hot melt extrusion (HME) and KinetiSol® Dispersing (KSD) were utilized to prepare dissolution-enhanced solid dispersions of Roche Research Compound A (ROA), a BCS class II drug. Preformulation characterization studies showed that ROA was chemically unstable at elevated temperatures and acidic pH values. Eudragit® L100-55 and AQOAT® LF (HPMCAS) were evaluated as carrier polymers. Dispersions were characterized for ROA recovery, crystallinity, homogeneity, and non-sink dissolution. Eudragit® L100-55 dispersions prepared by HME required the use of micronized ROA and reduced residence times in order to become substantially amorphous. Compositions containing HPMCAS were also prepared by HME, but an amorphous dispersion could not be obtained. All HME compositions contained ROA-related impurities. KSD was investigated as a method to reduce the decomposition of ROA while rendering compositions amorphous. Substantially amorphous, plasticizer free compositions were processed successfully by KSD with significantly higher ROA recovery values and amorphous character than those achieved by HME. A near-infrared chemical imaging analysis was conducted on the solid dispersions as a measure of homogeneity. A statistical analysis showed similar levels of homogeneity in compositions containing Eudragit® L100-55, while differences were observed in those containing HMPCAS. Non-sink dissolution analysis of all compositions showed rapid supersaturation after pH adjustment to approximately two to three times the equilibrium solubility of ROA, which was maintained for at least 24 h. The results of the study demonstrated that KSD is an effective method of forming dissolution-enhanced amorphous solid solutions in cases where HME is not a feasible technique