Jonge vertalers: met uitsterven bedreigd?

editorial reviewe

Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls (0.42 g). The effect of anti-YKL-40 on the increase of tumor volume started within hours after injection and was dose dependent. Intratumoral hemorrhage was observed in the treated animals. The strong effect on tumor size indicates important roles for YKL-40 in melanoma growth and argues for a careful evaluation of antibody therapy directed against YKL-40

Development of tumor volume with and without anti-YKL-40 treatment.

<p>T2 and T2* weighted MRI of two Balb/c scid mice with LOX tumors treated with isotype (<b>A</b>) or anti-YKL-40 monoclonal antibody (<b>B</b>) before injection of antibody (d0), five days (d5) and seven days (d7) after start of treatment. Observed hemorrhage is indicated by arrow.</p

La educación física desde una perspectiva interdisciplinar

Glosario al finalRecopila reflexiones y experiencias en educación infantil, primaria y secundaria sobre la educación física en relación con otras áreas. Fueron llevadas a cabo por docentes de educación física que apostaron por una enseñanza comprometida con la educación integral de la persona. Aporta experiencias para conocer otras culturas y adaptar la didáctica a estas. Plantea premisas para que el deporte sea un medio para la educación en valores y se relaciona con otras áreas como la lengua o la publicidad. Asimismo entre otras experiencias y propuestas sugiere el uso de material desechable en el deporte.CataluñaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Vessels and single S1P1 positive cells in the xenograft tumors: Immunohistochemical staining of anti-YKL-40 treated and control tumors for murine S1P1 (as in Figure 6B, right panel).

<p>Asterisks: vessels; arrows: Single S1P1 positive cells (<b>A</b>). Intratumoral bleeding leaves tumor tissue mostly intact: Histochemical Masson-Goldner staining of anti-YKL-40 treated and control tumors. nuclei: brown/black; connective tissue: green; erythrocytes: red (<b>B</b>).</p

Tumor growth as observed by MRI after injection of 10⁶ LOX melanoma cells during treatment with anti-YKL-40 monoclonal antibody or isotype control.

<p>For each animal, tumor volume calculated on basis of MRI data at each time point was divided by the tumor volume at day 0. <b>Black curve:</b> treatment with anti-YKL-40 antibody; <b>grey curve:</b> treatment with isotype control; **: P = 0.0011, two way ANOVA (<b>A</b>). T2* weighted MRI of two Balb/c scid mice with LOX tumors treated with isotype or anti-YKL-40 monoclonal antibody seven days after start of treatment. Observed hemorrhage is indicated by arrows (<b>B</b>).</p

Rapid effect of anti-YKL-40 treatment: T1 and T2 weighted MRI of two Balb/c scid mice with LOX tumors treated with anti-YKL-40 monoclonal antibody or isotype control before injection of antibody (d0), six hours (6 h) and 24 hours (24 h) after antibody injection.

<p>Bleeding can be seen as dark shades in the tumor (<b>A</b>). Two dissected tumors (each cut in half) 24 hours after i.v. treatment with anti-YKL-40 antibody or isotype treatment (<b>B</b>).</p

No significant difference in proliferation was observed between anti-YKL-40 treated and control tumors (N = 5, each).

<p>Given is the number of human Ki-67 positive cells per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>A</b>). Significant difference in vessel formation between anti-YKL-40 treated and control tumors (N = 5, each). Given is the percentage of murine S1P1 positive area per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>B</b>). No significant difference in leukocyte infiltration was observed between anti-YKL-40 treated and control tumors (N = 5, each). Given is the number of murine CD45 positive cells per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>C</b>).</p

LOX melanoma cells express YKL-40 <i>in vitro</i>: FACS anaylsis of <i>in vitro</i> expression of YKL-40 by LOX and U87 cells.

<p>There is a subpopulation of 21.1% with strong YKL-40 expression (M1) in the U87 cells (<b>A</b>). Anti-YKL-40 significantly reduces tube formation: Tube formation of HUVECs in U87 conditioned medium after 12 h. Medium was additionally supplemented with: Nothing (U87), 5 µg/ml anti-YKL-40 mononclonal antibody (5 µg/ml moAb) or 10 µg/ml anti-YKL-40 (10 µg/ml moAb). Representative photographs of wells with tube formation (upper panel) and column bar graph (means with SD, lower panel). The differences were significantly different (** : P = 0.0086, 1 way ANOVA) (<b>B</b>).</p

Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia

Purpose There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic variability in vitamin C transporter gene SLC23A2 could explain some inconsistencies in the literature. Methods Fruit/vegetable/vitamin C consumption from food frequency questionnaires and six low-penetrance genetic susceptibility polymorphisms in vitamin C transporter gene SLC23A2 (rs1715364, rs6133175, rs1776948, rs6139587, rs369270 and rs6052937) were examined in 434 CLL cases and 1257 randomly selected controls from primary care centres with genetic data of whom 275 cases and 1094 controls having both diet and genetic information. Logistic regression models were used to estimate odds ratio (OR) and 95 % confidence intervals (CI). Purpose There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic Results CLL patients were more likely to have a higher fruit consumption than controls (highest versus lowest quartile in g/day OR: 1.48; 95 % CI: 1.00 to 2.18; P = 0.03), whereas no associations were found with vegetable or total vitamin C intake. Based on log-additive models, rs6133175_A &gt; G (OR: 1.19, 95 % CI: 1.00 to 1.41; P = 0.05) and rs1776948_T &gt; A (OR: 1.20; 95 % CI: 1.01 to 1.41; P = 0.04) were associated with CLL. The haplogenotype analysis (rs1715364, rs6133175) supported the genotype results. No gene-diet interactions in CLL remained statistically significant after correction for multiple testing. Conclusions These data suggest that both fruit intake and genetic marker in SLC23A2 may play an independent role in CLL biology