The hallmarks of cancer.

Background The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. Methods We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide with (143 women) or without trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 ...

Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression In vitro, these cells differentiated into ECs In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis

http://science.sciencemag.org/content/sci/275/5302/964.full.pdf

Isolation of putative progenitor endothelial cells for angiogenesis.

Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.

Angiogenesis in cancer, vascular, rheumatoid and other disease

The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

TGF-beta signal transduction.

La presente invention concerne l'utilisation d'agonistes du recepteur de facteur de croissance de fibroblaste (FGFR) pour diagnostiquer, prevenir et/ou traiter les etats pathologiques comprenant, entre autres, les troubles d'hyperproliferation, les maladies osseuses et les troubles vasculaires. L'invention concerne en particulier l'utilisation d'agonistes de FGFR-4 agonistes, par ex. d'anticorps anti-FGFR-4. L'invention a egalement pour objet une composition pharmaceutique comprenant l'agoniste mentionne ci-dessus et une procedure de criblage.

Agonistes du fgfr

La presente invention concerne un inhibiteur de HER3 pour le traitement du melanome, en particulier des metastases de melanome et/ou un melanome refractaire, des compositions pharmaceutiques comprenant un tel inhibiteur et un procede pour le diagnostic ou le pronostic du melanome.

Her3 en tant que déterminant pour le pronostic du mélanome

InsR is the high-affinity receptor for the polypeptide hormone insulin and is a glycosylated cell surface protein with tyrosine kinase activity. It mediates the cellular actions of insulin, including stimulation of membrane transport processes (ions, glucose, and amino acids), stimulation of glycogen synthesis, lipogenesis and protein synthesis, inhibition of lipolysis, proteolysis and glycogenolysis, and growth-promoting effects in certain cell types. InsR functions as a membrane-bound PTK. Binding of insulin to the a subunits stimulates the tyrosine kinase activity of the β subunit, which leads torapid autophosphorylation of the β subunits, and phosphorylation of cytoplasmic polypeptides that are thought to be involved in receptor-specific signal transduction. The various functions of InsR can be assayed using binding of I-labeled insulin to calculate the number of receptors per cell, autophosphorylation to assess kinase activity, or stimulation of deoxyglucose uptake. InsR is expressed at low levels in all mammalian cell types but is expressed at much higher levels in liver, fat, and muscle.

- InsR: Insulin receptor (vertebrates)

Utilisation de ligands du recepteur Flk-1 pour la modulation de l'angiogenese et de la vasculogenese. Cette invention est basee en partie sur la preuve que l'expression du recepteur kinase tyrosine Flk-1 est associee aux cellules endotheliales et au fait que le facteur de croissance endothelial vasculaire (VEGF) ait ete identifie comme ligand a haute affinite du Flk-1. Ces resultats font ressortir le role predominant du Flk-1 dans le systeme de signalisation au cours de la vasculogenese et de l'angiogenese. L'invention porte sur l'elaboration de cellules hotes exprimant le Flk-1 et les utilisations de Flk-1 exprime pour evaluer et depister les medicaments et analogues de VEGF impliques dans la modulation du Flk-1 par une action agoniste ou antagoniste. L'invention porte egalement sur l'utilisation des ligands de Flk-1, y compris d'agonistes et d'antagonistes de VEGF, pour le traitement de certaines affections, dont le cancer, par modulation de la vasculogenese et de l'angiogenese.

Flk-1 UTILISE COMME RECEPTEUR POUR FACTEUR DE CROISSANCE ENDOTHELIAL VASCULAIRE

/pdf/regulation-des-immunstimulierenden-tumorassoziierten-antigen-4mn2u7xozc.pdf

Axel Ullrich

Papers

Agonistes du fgfr

Her3 en tant que déterminant pour le pronostic du mélanome

- InsR: Insulin receptor (vertebrates)

Flk-1 UTILISE COMME RECEPTEUR POUR FACTEUR DE CROISSANCE ENDOTHELIAL VASCULAIRE

Regulation des immunstimulierenden tumorassoziierten Antigen 90K in Ovarialkarzinomzellen