Sunitinib in advanced pancreatic neuroendocrine tumors: latest evidence and clinical potential

Based on preclinical data available in the RIP1-Tag2 transgenic mouse model, sunitinib is an inhibitor of angiogenesis in pancreatic neuroendocrine tumors blocking vascular endothelial growth factor receptors and platelet-derived growth factor receptors in endothelial cells and pericytes, respectively. Evidence of objective response in phase I trials justified the initiation of a large phase II/III program using sunitinib in patients with advanced/metastatic well-differentiated pancreatic neuroendocrine tumors. In the phase II study, sunitinib showed potent antitumor activity and a safe toxicity profile. In a recent double-blind placebo-controlled randomized phase III trial, sunitinib doubled the progression-free survival of patients, induced objective responses, and reduced the risk of death of patients with advanced/metastatic well-differentiated tumors. These data allowed the approval of sunitinib in several countries including Europe and the United States of America. These recent data provide hope for patients with well-differentiated pancreatic neuroendocrine tumors and will change standards of care in this disease

Distance Factors in the Foreign Market Entry of Software SMEs

Recent studies have indicated that the internationalization process of software SMEs is somewhat independent on the effect of psychic or geographic distance. However, these studies have analyzed the general pattern of entries where software SMEs not commonly follow a step-wise entry route from nearby countries to distant ones. Thus, it remains unknown what the effect of psychic and geographical distance is when these firms enter a distant foreign market. The findings in this case study reveal that psychic and geographic distance inhibited the foreign market entry of software SMEs. However, the distant foreign market entry of these firms was facilitated by distance-bridging and distance-compressing factors enabling foreign business operations despite the significant distance between the home and target country.peerReviewe

Pines

Pinus is the most important genus within the Family Pinaceae and also within the gymnosperms by the number of species (109 species recognized by Farjon 2001) and by its contribution to forest ecosystems. All pine species are evergreen trees or shrubs. They are widely distributed in the northern hemisphere, from tropical areas to northern areas in America and Eurasia. Their natural range reaches the equator only in Southeast Asia. In Africa, natural occurrences are confined to the Mediterranean basin. Pines grow at various elevations from sea level (not usual in tropical areas) to highlands. Two main regions of diversity are recorded, the most important one in Central America (43 species found in Mexico) and a secondary one in China. Some species have a very wide natural range (e.g., P. ponderosa, P. sylvestris). Pines are adapted to a wide range of ecological conditions: from tropical (e.g., P. merkusii, P. kesiya, P. tropicalis), temperate (e.g., P. pungens, P. thunbergii), and subalpine (e.g., P. albicaulis, P. cembra) to boreal (e.g., P. pumila) climates (Richardson and Rundel 1998, Burdon 2002). They can grow in quite pure stands or in mixed forest with other conifers or broadleaved trees. Some species are especially adapted to forest fires, e.g., P. banksiana, in which fire is virtually essential for cone opening and seed dispersal. They can grow in arid conditions, on alluvial plain soils, on sandy soils, on rocky soils, or on marsh soils. Trees of some species can have a very long life as in P. longaeva (more than 3,000 years)