Efficacy and Tolerability of Weekly Paclitaxel in Combination with High-dose Toremifene Citrate in Patients with Metastatic Breast Cancer

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.</p

Simulation study of helium bubble coalescence in tungsten at various temperatures relevant to fusion conditions

Molecular dynamics (MD) methods are used to study nanosized helium (He) bubble coalescence process in tungsten (W) at various temperatures relevant to fusion conditions, on an atomistic scale. Bubble coalescence in W is observed at a higher temperature and He/V ratio, while the calculated internal bubble pressure due to virial stress increases with the increase in the He/V ratio; bubble coalescence is significantly dependent on the bubble distance. In these MD simulations, coalescence occurs, only when the surface distance between the two bubbles is equal to 1a0, where a0 denotes the lattice constant and is approximately 0.317 nm at 2100 K. On the other hand, a bubble diameter between 1a0 and 3a0 may have relatively limited effect on the coalescence, although larger-sized bubbles may have higher migration energy. Local stress profile calculated indicates that initial bubbles can interact with each other, which may enhance the He atoms diffusion between bubbles and their coalescence. Physical contact at the initial stage of coalescence may occur between two nearby bubbles accompanied by W lattice distortion because of the limited displacement of W atoms near the bubbles and rapid migration of He atoms within the two bubbles. These results are beneficial for understanding the evolution of He bubbles in bulk W

Accurate Estimation of Brittle Fracture Toughness Deterioration in Steel Structures Subjected to Large Complicated Prestrains

Studies have suggested that brittle fractures occur in steel because microcracks in the brittle layer at grain boundaries propagate as a result of the increase in piled-up dislocations. Therefore, prestraining can approach the limits of a material, which could lead to a decrease in fracture toughness. However, strains are tensors comprising multiple components, so the effect of prestrain on fracture toughness is not simple. Additionally, the mechanism of change in critical stress due to prestrain has not been thoroughly investigated. For the lifetime evaluation of steel structures with a complicated load history, it is important to generalize the effect of complicated prestrain on the decrease in fracture toughness. In this paper, a single prestrain was applied in a direction different from the crack opening direction. A general three-point bending test was employed for fracture evaluation. Numerical analyses using the strain gradient plasticity (SGP) theory, which is a method based on the finite element method (FEM) are carried out; conventional macroscopic material damage rules are considered as well. Using these FEM analyses, the critical stress is calculated. Finally, the change in critical stress can be expressed by the yield point increase and dislocation density and formulated based on the identified micromechanisms

Establishment of damage estimation rule for brittle fracture after cyclic plastic prestrain in steel

Material damage caused by complicated prestrain like cyclic prestrain and various direction prestrain. It is so important to understand the mechanism of material damage for high-precision lifetime evaluation of steel structure. Material damage depends on not only equivalent plastic strain but the order of pestrain loaded. Also, material damage can be expressed by effective damage strain from back stress uploading and total dislocation density calculated from conventional mechanism based on strain gradient plasticity (CMSGP). These ideas can be extended to multiaxial problems and material damage can be estimated by these parameters as well as uniaxial problems

Behavior of a self-interstitial-atom type dislocation loop in the periphery of an edge dislocation in BCC-Fe

The behavior of the dislocation loop of a self-interstitial atom (SIA) near an edge dislocation and its conservative climb process were modeled in body-centered cubic Fe by incorporating loop rotation. The stable position of the loop and its rotational angle due to the interaction with an edge dislocation were evaluated through molecular dynamics simulations and calculations of the isotropic elasticity. The results were used as input variables in kinetic Monte Carlo simulations to model the absorption of the loop by the dislocation via a conservative climb. Loop rotation was found to affect the velocity of the conservative climb only at short-distances because the gradient in the interaction energy between the dislocation and an atom at the edge of the loop, which is a driving force of the conservative climb, could not be precisely evaluated without loop rotation. Depending on the distance between the dislocation and the loop, allowing the loop rotation resulted in either an increase or decrease in the velocity of the conservative climb

Mechanical Behavior of AISI 304SS Determined by Miniature Test Methods After Neutron Irradiation to 28 dpa

The mechanical properties of AISI 304 stainless steel irradiated for over a decade in the Experimental Breeder Reactor (EBR-II) were measured using miniature mechanical testing methods. The shear punch method was used to evaluate the shear strengths of the neutron-irradiated steel and a correlation factor was empirically determined to predict its tensile strength. The strength of the stainless steel slightly decreased with increasing irradiation temperature, and significantly increased with increasing dose until it saturated above approximately 5 dpa. An effective tensile strain hardening exponent was also obtained from the data which shows a relative decrease in ductility of steel with increased irradiation damage. Ferromagnetic measurements were used to observe and deduce the effects of the stress-induced austenite to martensite transformation as a result of shear punch testing