IAP1 es indispensable para la angiogenesis

Este nuevo articulo señala la importancia de IAP1 y NFkB en la angiogenesis, lo que nos provee de un nuevo blanco terapeutico.

Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis

Nature Genetics 39, 1397 (2007). doi:10.1038/ng.2007.8 Authors: Massimo M Santoro, Temesgen Samuel, Tracy Mitchell, John C Reed & Didier Y R Stainier

Integrity of the blood vessel wall is essential for vascular homeostasis and organ function. A dynamic balance between endothelial cell survival and apoptosis contributes to this integrity during vascular development and pathological angiogenesis. The genetic and molecular mechanisms regulating these processes in vivo are still largely unknown. Here, we show that Birc2 (also known as cIap1) is essential for maintaining endothelial cell survival and blood vessel homeostasis during vascular development. Using a forward-genetic approach, we identified a zebrafish null mutant for birc2, which shows severe hemorrhage and vascular regression due to endothelial cell integrity defects and apoptosis. Using genetic and molecular approaches, we show that Birc2 positively regulates the formation of the TNF receptor complex I in endothelial cells, thereby promoting NF-κB activation and maintaining vessel integrity and stabilization. In the absence of Birc2, a caspase-8–dependent apoptotic program takes place that leads to vessel regression. Our findings identify Birc2 and TNF signaling components as critical regulators of vascular integrity and endothelial cell survival, thereby providing an additional target pathway for the control of angiogenesis and blood vessel homeostasis during embryogenesis, regeneration and tumorigenesis.

NF-kappa B y ciclo celular

Este es un nuevo articulo muy interesante. Aunque ya se sabia que NF-kappa B algo tenia que ver con el ciclo celular (entre otros ver 'Int J Biochem Cell Biol.Tissue inhibitor of metalloproteinases-2 growth-stimulatory activity is mediated by nuclear factor-kappa B in A549 lung epithelial cells.Lizárraga F, Maldonado V, Meléndez-Zajgla J. ) este es uno de los mecanismos empleados para tal efecto.

A cell cycle regulatory network controlling NF-B subunit activity and function EMBO J advance online publication

Abstract

Aberrantly active NF-B complexes can contribute to tumorigenesis by regulating genes that promote the growth and survival of cancer cells. We have investigated NF-B during the cell cycle and find that its ability to regulate the G1-phase expression of key proto-oncogenes is subject to regulation by the integrated activity of IB kinase (IKK), IKK, Akt and Chk1. The coordinated binding of NF-B subunits to the Cyclin D1, c-Myc and Skp2 promoters is dynamic with distinct changes in promoter occupancy and RelA(p65) phosphorylation occurring through G1, S and G2 phases, concomitant with a switch from coactivator to corepressor recruitment. Akt activity is required for IKK-dependent phosphorylation of NF-B subunits in G1 and G2 phases, where Chk1 is inactive. However, in S-phase, Akt is inactivated, while Chk1 phosphorylates RelA and associates with IKK, inhibiting the processing of the p100 (NF-B2) subunit, which also plays a critical role in the regulation of these genes. These data reveal a complex regulatory network integrating NF-B with the DNA-replication checkpoint and the expression of critical regulators of cell proliferation.

Jefes de laboratorio

Creo que esto les puede interesar.
Saludos
http://scienceblogs.com/insolence/2007/10/what_kind_of_pi_am_i.php

Revision de IAPs

Una introduccion al tema que nos interesa, junto con la revision de survivina, para los interesados.

clipped from clincancerres.aacrjournals.org The Inhibitor of Apoptosis Proteins as Therapeutic Targets in Cancer poptosis is a cell suicide process with a major role in development and homeostasis in vertebrates and invertebrates. Inhibition of apoptosis enhances the survival of cancer cells and facilitates their escape from immune surveillance and cytotoxic therapies. Among the principal molecules contributing to this phenomenon are the inhibitor of apoptosis (IAP) proteins, a family of antiapoptotic regulators that block cell death in response to diverse stimuli through interactions with inducers and effectors of apoptosis. IAP proteins are expressed in the majority of human malignancies at elevated levels and play an active role in promoting tumor maintenance through the inhibition of cellular death and participation in signaling pathways associated with malignancies. Here, we discuss the role of IAP proteins in cancer and options for targeting IAP proteins for therapeutic intervention.

Revision de la importancia de la survivina en el cancer

No solo para diagnostico y tratamiento, sino para inmunoterapia. Magali tenia la idea de hacer un kit de ELISA para detectar survivina o sus anticuerpos en pacientes. Podria ser interesante

clipped from clincancerres.aacrjournals.org The Universal Character of the Tumor-Associated Antigen Survivin Several clinical trials targeting survivin with a collection of different approaches from small molecule antagonists to immunotherapy are currently under way. With regard to the latter, spontaneous anti-survivin T-cell reactivity has been described in cancer patients suffering from a huge range of cancers of different origin, e.g., breast and colon cancer, lymphoma, leukemia, and melanoma. Thus, survivin may serve as a universal target antigen for anticancer immunotherapy. Accordingly, down-regulation of survivin as a means of immune escape would severely inflict the survival capacity of tumor cells, which highlights this protein as a prime target candidate for therapeutic vaccinations against cancer. Data from several ongoing phase I/II trials targeting survivin for patients with advanced cancer will provide further information about this idea.

Estructura tridimensional de proteinas pasajeras cromosomales

Han cristalizado este complejo, que incluye survivina y que podria ser clave para la decision de apoptosis por la misma. El articulo completo en Jeyaprakash, A.A., Klein, U.R., Lindner, D., Ebert, J., Nigg, E.A., and Conti, E. (2007). Cell Vol 131, 230-231, 19 October 2007

clipped from images.cell.com

Ten Simple Rules for Getting Published

Este es un video interesante, por favor echenle un vistazo. Esta en ingles, pero lo principal aparece escrito. Es importante considerar este tipo de cuestiones para tener una carrera exitosa en la ciencia.
http://www.scivee.tv/pubcast/16261197

Celulas mesenquimales stem de MEDULA, podrian afectar el desarrollo del cancer

Cada vez se encuentran mas datos de la participacion del resto de la economia de nuestro organismo en la iniciacion y progresion del cancer.

clipped from 132.248.107.22:2062 New work with human breast cancer cells shows that they cooperate with mesenchymal stem cells (MSCs) derived from the bone marrow to advance metastasis. The breast cancer cells prompt MSCs to produce a cytokine, CCL5, that acts on cancer cells to promote their invasion and metastasis. Significantly, the MSC-stimulated cancer cells do not acquire a stable metastatic phenotype; rather they revert to their pre-malignant state in the absence of contextual signals. This raises the possibility that metastatic programming of cancer cells may be reversed therapeutically by targeting CCL5 or its receptor. Article: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis doi:10.1038/nature06188 4 October 2007

ademas

clipped from news.yahoo.com The Nobel is a particularly striking achievement for Capecchi, (pronounced kuh-PEK'-ee). A native of Italy, he was separated from his mother at age 4 when she was taken to the Dachau concentration camp as a political prisoner during World War II. For four years, Capecchi lived on the street or in orphanages, "and most of the time hungry," he recalled in a University of Utah publication in 1997. Malnutrition sent him to a hospital where his mother found him on his ninth birthday. Within two weeks they left for the United States, where he went to school for the first time, starting in third grade despite not knowing English.

Nobel de medicina

clipped from news.yahoo.com STOCKHOLM, Sweden - Two American scientists and a Briton won the 2007 Nobel Prize in medicine on Monday for groundbreaking discoveries that led to a powerful technique for manipulating mouse genes. The prize is shared by Mario R. Capecchi, 70, of the University of Utah in Salt Lake City; Oliver Smithies, 82, a native of Britain now at University of North Carolina in Chapel Hill, and Sir Martin J. Evans, 66, of Cardiff University in Wales.

Y finalmente, cual es el elemento mas importante?

En este paper, Kroemer nos demuestra la importancia de la respuesta inmune en el efecto de las drogas antineoplasicas, la cual podria ser uno de los determinantes de las diferencias en las respuestas particulares de cada paciente y, evidentemente, un blanco a explotar. Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature Med. 13, 1050–1059 (2007) | Article | PubMed |

clipped from www.signaling-gateway.org Immunology: 'Danger' signals Chemotherapy-induced cell death triggers the release of the high-mobility group box 1 protein (HMGB1), which stimulates Toll-like receptor 4 (TLR4) and elicits an immune response that is required for the success of the therapy.