Nuclear transport receptor karyopherin-α2 promotes malignant breast cancer phenotypes in vitro.

Tumorigenesis and tumor progression are associated with dysfunction of the nuclear transport machinery at the level of import and export receptors (karyopherins). Recent studies have shown that the nuclear import factor karyopherin-α2 (KPNA2) is a novel prognostic marker for poor prognosis in human breast cancer. Based on the well-defined hallmarks of cancer progression, we performed a detailed in vitro characterization of the phenotypic effects caused by KPNA2 overexpression and KPNA2 silencing in benign and malignant human breast cells. KPNA2 overexpression clearly increased proliferation of MCF7 tumor cells and further led to a reduction of cell-matrix adhesion in benign MCF10A cells, whereas cell migration was significantly increased (P<0.0001) in both tumor models. Remarkably, these individual effects of KPNA2 overexpression on proliferation, cell-matrix adhesion and migration resulted in an increased colony spreading of benign MCF10A breast cells and malignant MCF7 tumor cells (P<0.001), which is a hallmark of cancer progression. Conversely, RNA interference-mediated KPNA2 silencing caused a complete inhibition of MCF7 tumor cell proliferation and migration (P<0.0001). In addition, in these experiments apoptosis was increased (P<0.05) and formation of tumor cell colonies was reduced (P<0.01). Thus, KPNA2 overexpression provoked increased aggressiveness of malignant MCF7 breast tumor cells and induced a shift in benign MCF10A breast cells toward a malignant breast cancer phenotype. In conclusion, we demonstrate for the first time in experimental tumor models that forced KPNA2 expression drives malignant features relevant for breast cancer progression, while its silencing is required for the remission of those progressive phenotypes. This study gives clear evidence that KPNA2 acts as a novel oncogenic factor in human breast cancer, in vitro.

In vitro measurement conditions for optical coherence tomography (OCT).

CONCLUSION: Tissue marking with soot-covered fine needles enables the optical coherence tomography (OCT) scanning plane to be localized within the histological specimen to an accuracy of approximately 50 microm. Tissue water content is an especially important parameter for in vitro measurements. Dehydration tends to produce an increase in surface reflections and a reduction in imaging depth. OBJECTIVES: The aim of this in vitro study was to evaluate parameters relevant to the visualization and conservation process to allow optimal images to be generated for later differentiation between healthy and degenerated tissue in vivo. MATERIALS AND METHODS: Various methods of marking samples were applied in vitro to achieve accurate overlaps of the OCT scanning plane and the corresponding section of the histological specimen. The influence of temperature and tissue water content was investigated using both porcine and human tissue. Samples were marked using fine needles, ablation craters generated by laser application, and colour markers introduced into the tissue. RESULTS: It was demonstrated that the water content of tissue exerts a direct influence on OCT imaging, whereas above 15 degrees C temperature had no effect on image quality. With regard to the marking of samples, the best results were obtained using sooted fine needles.

Multiple tuning of birdcage resonators.

A theoretical framework is presented for designing birdcage resonators for MRI and MR spectroscopy. The analogy between the birdcage problem and the phonon problem in solid-state physics is used to achieve multiple tuning. Allowing that the capacitances in the columns of the cage assume unequal values, it is possible to achieve multiple tuning and simultaneously preserve the sinusoidal current distribution necessary to set a homogeneous magnetic field. Given the physical dimensions of the columns and branches of the cage as well as the desired resonant frequencies, the corresponding values of the capacitances can be calculated exactly. Closed-form expressions for the capacitances are given in terms of the mutual inductances and the desired resonant frequencies. A detailed analysis for a symmetrical low-pass birdcage is presented. The expressions for the resonant frequencies reduce to those given by other authors when only nearest-neighbor mutual inductances are included.