We have found that EGF-R expression is associated with the development of the Schwann cell-derive... more We have found that EGF-R expression is associated with the development of the Schwann cell-derived tumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGF-R, as did 7 of 7 other primary MPNSTs, a non-NF1 MPNST cell line, and the S100 + cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1-/mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1-/mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function.
Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to det... more Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to determine the maximum tolerated dose (MTD) of zosuquidar in combination with vinorelbine. The effects of zosuquidar on vinorelbine pharmacokinetics were also examined. Patients with advanced solid tumours were treated with escalating doses of zosuquidar administered every 8-12 h on days 7-9 and 14-16 during cycle 1 then days 0-2, 7-9, and 14-16 from cycle 2 onwards, with vinorelbine 22.5-30 mg/m2 IV on days 1, 8 and 15 every 28 days. Of 21 patients registered, 19 were treated at four dose levels (zosuquidar 100-300 mg/m2). Two patients had prolonged and febrile neutropenia at the second dose level resulting in a reduction of the dose of vinorelbine in subsequent dose levels. There was another patient with dose-limiting febrile neutropenia at dose level four which resulted in the expansion of the dose level three. Eight patients had stable disease and no objective responses were seen. Vinore...
Creating system setups for controlled performance evaluation experiments of distributed systems i... more Creating system setups for controlled performance evaluation experiments of distributed systems is time-consuming and expensive. Recreating experiment setups and reproducing experimental results that have been published by other researchers is even more challenging. In this paper, we present an experiment automation approach for evaluating distributed systems in compute cloud environments. We propose three concepts which should guide the design of experiment automation tools: (1) capture experiment plans in software modules, (2) run experiments in a publicly accessible cloud-based Elastic Lab, and (3) collaborate on experiments in an open, distributed collaboration system. We developed two tools which implement these basic concepts and discuss challenges and lessons learned during our implementation. An initial exemplary use case with Apache Cassandra on top of Amazon EC2 provides a first insight into the types of performance and scalability experiments enabled by our tools.
We have found that EGF-R expression is associated with the development of the Schwann cell-derive... more We have found that EGF-R expression is associated with the development of the Schwann cell-derived tumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGF-R, as did 7 of 7 other primary MPNSTs, a non-NF1 MPNST cell line, and the S100 + cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1-/mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1-/mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function.
Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to det... more Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to determine the maximum tolerated dose (MTD) of zosuquidar in combination with vinorelbine. The effects of zosuquidar on vinorelbine pharmacokinetics were also examined. Patients with advanced solid tumours were treated with escalating doses of zosuquidar administered every 8-12 h on days 7-9 and 14-16 during cycle 1 then days 0-2, 7-9, and 14-16 from cycle 2 onwards, with vinorelbine 22.5-30 mg/m2 IV on days 1, 8 and 15 every 28 days. Of 21 patients registered, 19 were treated at four dose levels (zosuquidar 100-300 mg/m2). Two patients had prolonged and febrile neutropenia at the second dose level resulting in a reduction of the dose of vinorelbine in subsequent dose levels. There was another patient with dose-limiting febrile neutropenia at dose level four which resulted in the expansion of the dose level three. Eight patients had stable disease and no objective responses were seen. Vinore...
Creating system setups for controlled performance evaluation experiments of distributed systems i... more Creating system setups for controlled performance evaluation experiments of distributed systems is time-consuming and expensive. Recreating experiment setups and reproducing experimental results that have been published by other researchers is even more challenging. In this paper, we present an experiment automation approach for evaluating distributed systems in compute cloud environments. We propose three concepts which should guide the design of experiment automation tools: (1) capture experiment plans in software modules, (2) run experiments in a publicly accessible cloud-based Elastic Lab, and (3) collaborate on experiments in an open, distributed collaboration system. We developed two tools which implement these basic concepts and discuss challenges and lessons learned during our implementation. An initial exemplary use case with Apache Cassandra on top of Amazon EC2 provides a first insight into the types of performance and scalability experiments enabled by our tools.
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