This model provides a conceptual framework and a reproducible in vivo system to study unresolved central questions in cancer biology regarding the initiation, reversibility, and molecular regulation of the timing of the angiogenic switch.

Angiogenesis is crucial for tumor growth. Angiogenesis inhibitors, such as O-(chloracetyl-carbamoyl) fumagillol (TNP-470), are thus emerging as a new class of anticancer drugs. In clinical trials, TNP-470 slowed tumor growth in patients with metastatic cancer. However, at higher doses necessary for tumor regression, many patients experienced neurotoxicity. We therefore synthesized and characterized a water-soluble conjugate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, Gly-Phe-Leu-Gly linker and TNP-470. This conjugate accumulated selectively in tumor vessels because of the enhanced permeability and retention (EPR) effect. HPMA copolymer-TNP-470 substantially enhanced and prolonged the activity of TNP-470 in vivo in tumor and hepatectomy models. Polymer conjugation prevented TNP-470 from crossing the blood-brain barrier (BBB) and decreased its accumulation in normal organs, thereby avoiding drug-related toxicities. Treatment with TNP-470 caused weight loss and neurotoxic effects in mice, whereas treatment with the conjugate did not. This new approach for targeting angiogenesis inhibitors specifically to the tumor vasculature may provide a new strategy for the rational design of cancer therapies.

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

We investigated the storage of carbon (C) in the soil, litter and various phytomass compartments in a 69-year-old Scots pine (Pinus sylvestris L.) stand in the Belgian Campine region, Brasschaat, Belgium. The total amount of C stored in the stand was 248.9 t•ha-1 , 47 % of which was in soil organic matter, 11 % in surface litter and 42 % in phytomass. More than 60 % of total C was stored belowground. Total phytomass C in the stand was 104 t•ha-1 ; most phytomass C was found in the stems (70 %). The root system was very shallow and contained only 14 % of the phytomass C, most of it in the coarse roots. Although total live fine root (< 1 mm) length was high (3.3 km•m-2), fine roots contributed only 2 % to total phytomass. (© Inra/Elsevier, Paris.) carbon storage / phytomass / Pinus sylvestris / roots / Scots pine Résumé-Phytomasse aérienne et souterraine et stock de carbone dans un peuplement de pin sylvestre en Belgique. Nous avons étudié le stockage du carbone dans le sol, dans la litière et dans différents compartiments de la phytomasse d'une plantation de pins sylvestre (Pinus sylvestris L.), âgés de 69 ans, localisée à Brasschaat, région de la Campine, Belgique. La quantité totale de carbone stockée au niveau de cette plantation était de 248,9 t ha-1. 47 % étaient localisés dans la matière organique du sol, 11 % dans la litière, et 42 % dans la phytomasse. Plus de 60 % de la quantité totale de carbone se trouvait dans le sous-sol. La quantité de carbone contenue dans la phytomasse était de 212 t ha-1. La plus grande partie de ce dernier a été trouvé dans les tiges (70 %). Le système racinaire était très superficiel et ne contenait que 14 % du carbone de la phytomasse, principalement localisé dans les grosses racines. Bien que la longueur des racines fines et vivantes ait été importante (3,3 km m-2), elles ne représentaient que 2 % de la phytomasse totale. (© Inra/Elsevier, Paris.

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