A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

12 p.

Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

Background: The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D) growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods: The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of <300 mu m in diameter, produced by the hanging-drop method to mimic the microenvironment of avascular micrometastases prior to hypoxia occurrence. Results: Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF) secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE) cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA)-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM)-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX)-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion: 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

IPCC WGII Fifth Assessment Report (AR5): Expanding the solution space for adaptation

6 p.

Quinto informe de evaluación (AR5) del GT-II del IPPC: aumentando el espacio de las soluciones para la adaptación

6 p.

IPPC-ren II. lan-taldearen bosgarren ebaluazio txostena (AR5): egokitzerako konponbideeremua zabaltzen

6 p.

Klima-aldaketaren eraginak euskal kostaldeko mendebaldeko sakonera handiko begetazio azpimarealean

[eus] Euskal kostaldeko mareazpiko begetazioak aldaketa esanguratsuak jasan ditu azken hiru hamarkadetan. Aurretik egindako ikerketek jakinarazi dute aldaketa horiek klima-aldaketak eragindakoak direla. Ikerketa honen helburua inpaktu horri buruzko informazio gehiago lortzea da. Horretarako, sakonera handiko uretako fitobentosaren osaerari eta ugaritasunari buruzko balioespena egin da. 2014. urteko udan 7 trantsektu ezarri ziren, Kobaroneko muturretik Muskizeko muturreraino. Trantsektu horiek aurretik ikertuak izan ziren 1982 eta 2007 urteetan, eta laginketa suntsitzailea egin zen. Analisi estatistikoek aldaketa esanguratsuak erakusten dituzte sakoneko (9-11m) komunitateetan azken 32 urteetan. Uraren tenperaturaren emendioa eta eguzki-erradiazio altuagoa detektatutako aldaketen erantzuleak izan daitezke neurri batean. Pterosiphonia complanata espezie esziafiloaren gainbeherak eta Cystoseira baccata eta Aphanocladia stichidiosa espezieen ugaritzeak hipotesi hori azaltzen dute. Espero genuenaren kontra, Gelidium corneum espeziea, sakontasun gutxiko uretan gainbehera bortitza jasaten ari dena, ez da 9 metrotik beherako sakonerara lekualdatu. Hala ere, ezin da ziurtatu egungo ingurumeneko baldintzak optimoak ez direnik G. corneum espeziearen garapenerako 9-11 metroko sakoneretan. Migrazio bertikal hori ez gertatzearen arrazoi onargarriena C. baccata- rekiko lehiakortasuna dela dirudi. Bestalde, C. baccata hiru dimentsiotako habitatak eratzeko gai den tamaina handiko alga bat da, espezie askorentzat babesleku gisa diharduena. Ondorioz, haren hedapenak G. corneum-ek sakonera txikiagoetan betetzen zuen funtzioa ordezka lezake neurri batean.