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PURPOSE Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. METHODS Patients with HER-2-positive breast cancer that progresses(More)
The generation of phosphatidylinositide 3-phosphates has been observed in a variety of cellular responses. The enzymes that mediate synthesis are the phosphoinositide 3-kinases (PI3-Ks) that form a family of structurally diverse enzymes with distinct substrate specificities. In this paper, we describe the cloning of a novel human PI3-K, namely PI3-K-C2(More)
Phosphoinositide (PI) 3-kinases have been characterized as enzymes involved in receptor signal transduction in mammalian cells and in a complex which mediates protein trafficking in yeast. PI 3-kinases linked to receptors with intrinsic or associated tyrosine kinase activity are heterodimeric proteins, consisting of p85 adaptor and p110 catalytic subunits,(More)
The phosphoinositide 3-kinases (PI3-kinases) are a ubiquitously expressed enzyme family that, through the generation of phospholipid second messengers, play a key role in the regulation of many cellular processes. These include motility, proliferation and survival, and carbohydrate metabolism. Members of the PI3-kinase family and related kinases, their(More)
Normal human luminal and myoepithelial breast cells separately purified from a set of 10 reduction mammoplasties by using a double antibody magnetic affinity cell sorting and Dynabead immunomagnetic technique were used in two-dimensional gel proteome studies. A total of 43,302 proteins were detected across the 20 samples, and a master image for each cell(More)
The phosphoinositide 3-kinases (PI3-kinases) are a family of lipid kinases that have a key role in the regulation of many cellular processes including proliferation, survival, carbohydrate metabolism, and motility. There is now strong evidence that some members of the PI3-kinase family have an important role in cancer. Emerging evidence for functional(More)
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report herein the cloning and characterization of p110delta, a novel class I PI3K. Like p110alpha and p110beta, other class I PI3Ks, p110delta displays a broad(More)
Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three(More)
Mammary stromal tissue has a major role in the control and regulation of physiological processes in the breast. Recently, the function of stroma in supporting the tumourigenic process as well as responding to the oncogenic lesion has become clearer. This review differs from the conventional view in that it focuses on and discusses the newly available(More)
A total of 34 patients with advanced cancer were given weekly or daily escalating doses of oral gossypol, a cottonseed-oil constituent showing evidence of antineoplastic activity in pre-clinical studies. No major adverse events occurred and there was no evidence of haematological or biochemical disturbance. As determined by dose escalation in 17 patients,(More)