Strong expression of ID1 protein is associated with decreased survival, increased expression of ephrin-A1/EPHA2, and reduced thrombospondin-1 in malignant melanoma

The ID1 protein, an inhibitor of basic helix–loop–helix transcription factors, has been involved in multiple cellular processes including cell cycle regulation, apoptosis, and angiogenesis. To evaluate the importance of ID1 in malignant melanoma, tumour cell expression was examined by immunohistochemistry in 119 cases of nodular melanoma using tissue microarray technique, and related to multiple tumour markers including proliferation, p16 expression, angiogenesis and patient survival. Strong ID1 expression was significantly associated with increased tumour thickness, and significantly reduced survival. Also, increased ID1 was associated with loss of thrombospondin-1 (TSP-1) expression, a known inhibitor of angiogenesis, and increased intensity of ephrin-A1 and its receptor EPHA2. Presence of BRAF mutations was related to strong ID1 expression, but there was no relationship with p16 protein expression. Further, no significant correlation was found between ID1 and microvessel density. In conclusion, our study supports a significant role of the ID1 protein in melanoma progression and patient prognosis. The absence of correlation with p16 protein expression and angiogenesis suggests that other regulatory pathways and mechanisms might be influenced by ID1 in melanomas. An inverse relation between ID1 and TSP-1 expression support an important role of ID1 in the regulation of this complex multitarget protein

Subduction and continental collision in the Eastern Mediterranean during the closure of the Tethyan gateway

Plate tectonics and mantle dynamics controlled the continental collision and tectonics of the Eastern Mediterranean – Tethyan realm, including by closing the Tethys Seaway linking the Atlantic and Indo-Pacific oceans. This led to reorganizations in ocean circulation, diversification and migration of marine and terrestrial species, and climatic change. Here, I review some of the work on the geodynamics of the region, including on the evolution of topography, and how paleotopography was influenced by mantle convection and volcanism. Mantle convection appears to have had a significant impact on the paleoenvironment, including by ultimately establishing the Gomphotherium Landbridge in the Miocene, enabling greater faunal exchanges between Africa-Arabia and Eurasia

Tumor necrosis is associated with increased alphavbeta3 integrin expression and poor prognosis in nodular cutaneous melanomas

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival.</p> <p>Methods</p> <p>A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (α_vβ₃integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins.</p> <p>Results</p> <p>Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of α_vβ₃integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67).</p> <p>Conclusion</p> <p>Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased α_vβ₃integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored.</p

Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

<p>Abstract</p> <p>Background</p> <p>Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables.</p> <p>Methods</p> <p>202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm²) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections.</p> <p>Results</p> <p>Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis.</p> <p>Conclusions</p> <p>Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.</p

ESA's wind Lidar mission ADM-AEOLUS; on-going scientific activities related to calibration, retrieval and instrument operation

The Earth Explorer Atmospheric Dynamics Mission (ADM-Aeolus) of ESA will be the first-ever satellite to provide global observations of wind profiles from space. Its single payload, namely the Atmospheric Laser Doppler Instrument (ALADIN) is a directdetection high spectral resolution Doppler Wind Lidar (DWL), operating at 355 nm, with a fringe-imaging receiver (analysing aerosol and cloud backscatter) and a double-edge receiver (analysing molecular backscatter). In order to meet the stringent mission requirements on wind retrieval, ESA is conducting various science support activities for the consolidation of the on-ground data processing, calibration and sampling strategies. Results from a recent laboratory experiment to study Rayleigh-Brillouin scattering and improve the characterisation of the molecular lidar backscatter signal detected by the ALADIN double-edge Fabry- Perot receiver will be presented in this paper. The experiment produced the most accurate ever-measured Rayleigh-Brillouin scattering profiles for a range of temperature, pressure and gases, representative of Earth’s atmosphere. The measurements were used to validate the Tenti S6 model, which is implemented in the ADM-Aeolus ground processor. First results from the on-going Vertical Aeolus Measurement Positioning (VAMP) study will be also reported. This second study aims at the optimisation of the ADM-Aeolus vertical sampling in order to maximise the information content of the retrieved winds, taking into account the atmospheric dynamical and optical heterogeneity. The impact of the Aeolus wind profiles on Numerical Weather Prediction (NWP) and stratospheric circulation modelling for the different vertical sampling strategies is also being estimated

The recurrence pattern following delayed breast reconstruction after mastectomy for breast cancer suggests a systemic effect of surgery on occult dormant micrometastases

The purpose of this study was to characterize the recurrence dynamics in breast cancer patients after delayed reconstruction. We hypothesized that surgical reconstruction might stimulate dormant micrometastases and reduce time to recurrence. All mastectomy breast cancer patients with delayed surgical reconstruction at Haukeland University Hospital, between 1977 and 2007, n\ua0=\ua0312, were studied. Our control group consisted of 1341 breast cancer patients without reconstruction. For each case, all patients in the control group with identical T and N stages and age\ua0\ub12\ua0years were considered. A paired control was randomly selected from this group. 10\ua0years after primary surgery, 39 of the cases had relapsed, compared to 52 of the matched controls. The reconstructed group was analyzed for relapse dynamics after mastectomy; the first peak in relapses was similarly timed, but smaller than for the controls, while the second peak was similar in time and size. Second, the relapse pattern was analyzed with reconstruction as the starting point. A peak in recurrences was found after 18\ua0months, and a lower peak at the 5th\u20136th year. The height of the peak correlated with the extent of surgery and initial T and N stages. Timing of the peak was not affected, neither was the cumulative effect. The relapse pattern, when time origin is placed both at mastectomy and at reconstruction, is bimodal with a peak position at the same time points, at 2\ua0years and at 5\u20136\ua0years. The timing of the transition from dormant micrometastases into clinically detectable macrometastases might be explained by an enhancing effect of surgery