Search Results - (Author, Cooperation:S. D. Baker)

2011-03-11

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Acetylation ; CREB-Binding Protein/chemistry/*genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic/genetics ; Gene Expression Regulation, Neoplastic ; Histone Acetyltransferases/genetics/metabolism ; Histones/metabolism ; Humans ; Mutation/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics ; Protein Structure, Tertiary/genetics ; Recurrence

2018-11-16

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Geosciences

Computer Science

Medicine

Natural Sciences in General

Physics

Biochemistry

article

2006

Reliabilität ; Testkonstruktion ; Multiple-Choice-Verfahren ; Testentwicklung ; Kraft (Phys) ; Physik

American journal of physics, Bd. 74 (2006) H. 5, S. 449-453, 0002-9505

1943-2909

English

1569-8041

colorectal cancer ; granulocyte-colony stimulating factor ; pharmacokinetics ; phase II ; topotecan

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: The premise for the study was that topotecan (TPT) resistance in preclinical studies is associated with low level expression of the p-glycoprotein (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR) phenotype, which might be overcome in clinical practice by administering moderately (2.3-fold) higher doses of TPT that have been shown to be feasible with granulocyte colony-stimulating factor (G-CSF) support. This phase II study evaluated the anti-tumor activity of TPT administered at its highest possible solid tumor dose with G-CSF in patients with fluoropyrimdine-refractory advanced colorectal carcinoma. The study also sought to identify pharmacodynamic (PD) determinants of both activity and toxicity. Patients and methods: TPT was administered as a 30-minute infusion daily for five days every three weeks at a dose of 3.5 mg/m2/day to patients with advanced colorectal carcinoma who developed progressive disease either during treatment with fluoropyrimidine-based chemotherapy for advanced disease or within six months after receiving fluoropyrimdine-based adjuvant chemotherapy. This dose of TPT was previously determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I study involving solid tumor patients with similar risk factors for myelosuppression. Plasma sampling was performed during course 1 to characterize the pharmacokinetic (PK) and PD behavior of TPT. Results: Seventeen patients who received 89 courses of TPT and G-CSF were evaluable for toxicity; 16 patients were evaluable for anti-tumor response. Toxicity, particularly myelosuppression, was substantial. At the 3.5 mg/m2/day dose level, absolute neutrophil counts (ANC) were less than 500/µl for longer than five days in 17% of courses involving seven of 17 (41%) patients. Severe neutropenia associated with fever occurred in 12.3% of courses; and platelet counts below 25,000/µl were noted in 26.9% of courses. These toxicities resulted in dose reductions in seven of 17 (41%) patients. Nevertheless, 90% of the planned total dose of TPT was administered. No major responses were observed, though minor activity was noted in several patients. Both the median time to progression and the median survival time were short – 2.5 and four months, respectively. Although interindividual variability in the disposition of total TPT was observed, the lack of objective responses precluded PD assessments related to disease activity. Total TPT exposure was significantly higher than drug exposure achieved in similar patients at an identical dose in a previous phase I study of TPT and G-CSF, which may explain why more severe myelosuppressive effects occurred in the present study. There were no PD relationships evident between relevant PK parameters and the percent decrements in platelets and ANCs during course 1, although patients with severe toxic effects (ANC below 500/µl for more than five days and/or platelets 〈25,000/µl) had higher drug exposure than patients with less severe toxicity (P 〈 0.018 and P = 0.09, respectively). Conclusions: Based on these results, the true response rate of TPT at its solid tumor MTD with G-CSF support is unlikely to approach 20%. Although a response rate of less than 20% might be viewed as significant in this disease setting and might be confirmed with sufficient statistical certainty by treating additional patients, the substantial toxicity, inconvenience, and cost associated with this high dose TPT/G-CSF regimen does not warrant the acceptance of a lower level of anti-tumor activity as a criterion for further development.

Electronic Resource

1569-8041

DMP 840 ; pharmacodynamics ; pharmacokinetics ; phase I

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840. Patients and methods: Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. Results: A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25–86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P 〈 0.01, Wilcoxon Rank Sum test). Conclusion: The recommended dose of DMP 840 for further disease oriented evaluations is 40 mg/m2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.

Electronic Resource

1432-0630

77.55 ; 81.15

Springer Online Journal Archives 1860-2000

Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics

Physics

Abstract This paper reviews the production of silicon oxide thin films using a novel photoenhanced deposition technique incorporating a windowless nitrogen discharge lamp contained within the deposition vessel. This process has the potential to produce better semiconductor/insulator interfaces than those produced using conventional RF glow discharge techniques, since there is no damage to the growing film surface from energetic ions produced in the glow discharge plasma. The use of an internal lamp obviates the need for a window between the lamp and reaction chamber and thus overcomes the problems of attenuation of short wavelength ultraviolet radiation by the window. All the ultraviolet output of the lamp can now directly couple into the reaction gases, so the need for sensitising agents is also removed. Thin films of silicon oxide have been deposited onto single crystal silicon wafers from nitrous oxide-silane gas mixtures. The physical properties are comparable to those of high quality insulator films deposited by plasma enhanced techniques. The results of electrical measurements indicate that this material is of sufficiently high quality to be used as a low temperature deposited gate dielectric for thin film devices. To confirm this, thin film transistors (TFTs) have been fabricated using the material (and an active layer of amorphous silicon deposited in the same system) and characteristics of these TFTs are also presented.

Electronic Resource

1432-0630

77.55 ; 81.15

Springer Online Journal Archives 1860-2000

Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics

Physics

Abstract This paper reviews the production of silicon oxide thin films using a novel photoenhanced deposition technique incorporating a windowless nitrogen discharge lamp contained within the deposition vessel. This process has the potential to produce better semiconductor/insulator interfaces than those produced using conventional RF glow discharge techniques, since there is no damage to the growing film surface from energetic ions produced in the glow discharge plasma. The use of an internal lamp obviates the need for a window between the lamp and reaction chamber and thus overcomes the problems of attenuation of short wavelength ultraviolet radiation by the window. All the ultraviolet output of the lamp can now directly couple into the reaction gases, so the need for sensitising agents is also removed. Thin films of silicon oxide have been deposited onto single crystal silicon wafers from nitrous oxide-silane gas mixtures. The physical properties are comparable to those of high quality insulator films deposited by plasma enhanced techniques. The results of electrical measurements indicate that this material is of sufficiently high quality to be used as a low temperature deposited gate dielectric for thin film devices. To confirm this, thin film transistors (TFTs) have been fabricated using the material (and an active layer of amorphous silicon deposited in the same system) and characteristics of these TFTs are also presented.

Electronic Resource