Eukaryotic Initiation Factor 4E (eIF4E) and angiogenesis: prognostic markers for breast cancer

BACKGROUND: The overexpression of eukaryotic translation initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of human breast cancer. This study investigates the relationship between eIF4E and angiogenesis, as well as their prognostic impact in patients with human breast cancer. METHODS: Immunohistochemical staining was used to determine protein expression of eIF4E, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and CD105 in a set of 122 formalin-fixed, paraffin-embedded primary breast cancer tissues. Expression of eIF4E in positive cells was characterized by cytoplasmic staining. Evaluation of VEGF and IL-8 in the same tissue established the angiogenic profiles, while CD105 was used as an indicator of microvessel density (MVD). RESULTS: A significant relationship was found between the level of eIF4E expression and histological grade (P = 0.016). VEGF, IL-8, and MVD were closely related to tumor grade (P = 0.003, P = 0.022, and P < 0.001, respectively) and clinical stage (P = 0.007, P = 0.048, and P < 0.001, respectively). Expression of eIF4E was also significantly correlated with VEGF (P = 0.007), IL-8 (P = 0.007), and MVD (P = 0.006). Patients overexpressing eIF4E had significantly worse overall (P = 0.01) and disease-free survival (P = 0.006). When eIF4E, histological grade, tumor stage, ER, PR, Her-2 status and the levels of VEGF, IL-8, MVD were included in a multivariate Cox regression analysis, eIF4E emerged as an independent prognostic factor for breast cancer (P = 0.001), along with stage (P = 0.005), node status (P = 0.046), and MVD (P = 0.004). CONCLUSION: These results suggest that higher eIF4E expression correlates with both angiogenesis and vascular invasion of cancer cells, and could therefore serve as a useful histological predictor for less favorable outcome in breast cancer patients, as well as represent a potential therapeutic target

Seismic site characterization of the Kastelli (Kissamos) Basin in northwest Crete (Greece): Assessments using ambient noise recordings

Crete is actively seismic and site response studies are needed for estimating local site conditions subjected to seismic activity. In order to collect basic data, we performed ambient noise recordings to estimate the site response of the surface and near subsurface structure of the small-scale Kastelli Basin in northwest Crete. The spatial horizontal to vertical spectral ratios (HVSR) resonance pattern of the investigated sites in the centre of the Basin consists of either one or two peaks divided into low to high frequency range in different sites as follows: (a) in some sites only one amplified peak at low frequencies (0.6–1.2 Hz), (b) in other sites only one amplified peak at medium frequencies (2.9–8.5 Hz) and (c) in yet other sites two amplified peaks in the low to high frequency range (0.6–15.5 Hz). The investigated sites are amplified in the frequency range 0.6–15.5 Hz, while the amplitude reaches to a factor of 4 in the spectral ratios. The one HVSR amplified peak at low frequencies is related to locally soft or thick Quaternary deposits. Microtremors were measured in the coastal northwest part of the Basin in a well—lithified Cretaceous limestone site characterized by fractures and faults striking predominantly in a sector NNE to NNW. Sites of one amplified peak at medium frequencies are extended from coastal northwest to southwest delineating a structure striking to NNW. The two amplified peaks are attributed to shallow subsurface heterogeneities/irregularities, locally induced by fault zones and to the overlying Quaternary deposits. Spatial HVSR variations in the frequency and HVSR shape delineate four structures striking NNE, NNW and in a sector NW to WNW, crosscutting the dense populated Basin suggesting that microtremors could be a valuable tool for providing a first approximation of fault zone delineation at least for the Kastelli-Kissamos Basin. The Basin is classified into the X soil category of the Greek Seismic Code 2000.This work was implemented through the project entitled “Interdisciplinary Multi-Scale Research of Earth-quake Physics and Seismotectonics at the Front of the Hellenic Arc (IMPACT-ARC)” in the framework of action “ARCHIMEDES III—Support of Research Teams at TEI of Crete” (MIS380353) of the Operational Program “Education and Lifelong Learning” and is co-financed by the European Union (European Social Fund) and Greek national fund