The patient experience

The impact of improved treatments for the management of hormone-sensitive breast cancer extends beyond clinical responses. Thanks to appropriate literature and access to the internet, patient awareness of treatment options has grown and patients are now, in many cases, able to engage their oncologists in informed conversations regarding treatment and what to expect in terms of efficacy and safety. Indeed, patients realize that although there is no cure for metastatic disease, treatment can greatly reduce the risk of progression and in the adjuvant setting, where treatment is administered with a curative intent, current treatment options reduce the risk of relapse. The approval of letrozole throughout the breast cancer continuum has provided patients with many reassuring options. The improvement in outcome with letrozole is achieved without a detrimental effect on overall quality of life. Adverse events such as hot flushes, arthralgia, vaginal dryness, and potential osteoporosis are most significant from the patient’s perspective, and it is important that caregivers pay attention to patients experiencing these events, as they can impact compliance unless effectively explained and managed. The major benefits of letrozole are to improve prospects for long-term survivorship in the adjuvant setting and to delay progression and the need for chemotherapy in the metastatic setting

Blinking suppression and intensity recurrences in single CdSe-oligo (phenylene vinylene) nanostructures: experiment and kinetic model

We report time-resolved single molecule fluorescence imaging of individual CdSe quantum dots that are functionalized with oligomeric conjugated organic ligands. The fluorescence intensity trajectories from these composite nanostructures display both a strong degree of blinking suppression and interesting intensity fluctuations with recurrence times on the order of 10-60 seconds (quantified by Fourier transform analysis). In addition, Time-Tagged-Time-Resolved (TTTR) fluorescence measurements of the fluorescence decay rate of individual hybrid nanostructures indicate significantly modified non-radiative decay rates relative to conventional ZnS-capped CdSe quantum dots. Modeling of fluorescence intensity trajectories using a diffusive reaction coordinate model shows that slow fluctuations in electron energies (1Se, 2Pe) can give rise to the recurrences via modified Auger-assisted hole-trapping rates. We briefly discuss a possible ligand-induced mechanism for such behavior

TGFbeta2 and TbetaRII are valid molecular biomarkers for the antiproliferative effects of tamoxifen and tamoxifen metabolites in breast cancer cells

The original publication can be found at www.springerlink.comResponse to treatment with the antiestrogen tamoxifen is variable and at least partially due to its highly complex metabolism. Tamoxifen is transformed by polymorphic and inducible cytochrome P450 enzymes to a large number of metabolites with varying biological activities. The estrogen receptor dependent growth inhibitory effect of antiestrogens is mediated by activation of antiproliferative Transforming Growth Factor beta (TGFβ) signal transduction pathways. The aim of the present study was to establish if TGFβ2 or TGFβ receptor II (TβRII), could be used as markers to assess the pharmacological potency of tamoxifen and its metabolites. Consequently, we analyzed the growth inhibitory effect of tamoxifen and its major metabolites and explored whether it correlated with their capacity to induce TGFβ2 and TβRII expression. Human breast cancer cells (MCF-7 and T47D) were treated with tamoxifen and tamoxifen metabolites and mRNA expression of TGFβ2 and TβRII was analyzed by quantitative RT-PCR. Only two metabolites 4-hydroxytamoxifen and N-desmethyl-4-hydroxytamoxifen had significant antiproliferative activity and were able to induce TGFβ2 and TβRII. Plasma concentrations of these metabolites are usually very low in patients. However, even minor growth inhibitory effects at concentrations which are below the limit of quantification in plasma samples resulted in clearly discernible effects on expression of TGFβ2 and TβRII. Taken together, our data demonstrate that TGFβ2 and TβRII are very specific and sensitive biomarkers for the antiestrogenic activity of tamoxifen metabolites in breast cancer.Miriam B. Buck, Janet K. Coller, Thomas E. Mürdter, Michel Eichelbaum and Cornelius Knabb