Huanglian is an herb that is widely used in China for the treatment of gastroenteritis. We elected to determine whether huanglian could inhibit tumor cell growth by modulating molecular events directly associated with the cell cycle. Huanglian inhibited tumor growth and colony formation of gastric, colon, and breast cancer cell lines in a time- and dose-dependent manner. Cell growth was completely inhibited after 3 days of continuous drug exposure to 10 microg/ml of herb. This degree of growth inhibition was significantly greater than that observed with berberine, the major constituent of the herb. The inhibition of cell growth by huanglian was associated with up to 8-fold suppression of cyclin B1 protein. This resulted in complete inhibition of cdc2 kinase activity and accumulation of cells in G(2). The mRNA expression of cyclin B1 was not changed after huanglian treatment. There was no change in the protein expression of cyclins A or E. Therefore, the effect of huanglian on inhibiting tumor growth seems to be mediated by the selective suppression of cyclin B1, which results in the inhibition of cdc2 kinase activity. Inhibition of cyclin dependent kinase (cdk) activity is emerging as an attractive target for cancer chemotherapy. Huanglian represents a class of agents that can inhibit tumor cell growth by directly suppressing the expression of a cyclin subunit that is critical for cell cycle progression. These results indicate that traditional Chinese herbs may represent a new source of agents designed for selective inhibition of cyclin dependent kinases in cancer therapy.

Background-Torsion is an essential component of left ventricular (LV) function. Systolic rotation, as a component of torsion, winds the heart muscle up like a spring, setting up recoil for early diastole. We used a new two-dimensional (2D) speckle tracking strain method to study differences in twisting in sub-endocardial and sub-epicardial layers of the left ventricle in open-chest pigs. Our aim was to identify the relative contributions of the inner or outer layers of the LV wall to rotation and hence systole.

The 2DSR program can be used to study twisting action of the heart.

This new technology is a first step in the integration of ICE with EP procedures.

Background: We have developed a method for spatially-dense 3D speckle tracking that tracks speckle features in myocardium to allow calculation of full 3D displacement and strain from 4D full-volume echo images and have tested its accuracy compared to sonomicrometry in open-chest pigs. Methods: The 4D images were acquired using a Philips iE33 on 6 open-chest piglets. An array of 6 sonomicrometers (sono crystals) was implanted as 2 triangular sets at apex and mid-levels in the LV myocardium. The pair-wise crystal distances were computed offline using Sonometrics® software to yield 3D displacements. For 4D computation of speckle based mechanics, Cartesian coordinate images were entered into an envelope detection program, then a volume-based non-rigid registration was used to obtain optimal displacement between end diastolic (ED) and end systolic (ES) volumes. The displacement field was modeled using B-splines, parameterized by the location of a set of control points. Optimal locations of the control points were obtained by minimizing the sum of squared intensity differences between the ED and ES volumes. Sono crystals were located based on anatomic markers in the ED volume before the adjacent speckle patches were tracked, to ensure that image-derived strains were computed for segments matching the distances between sono crystal pairs. The method was implemented in MATLAB. Results: The comparison of the systolic strains from dense 4D speckle tracking showed a strong correlation (r 2 = 0.82) with sonomicrometry for 44 segmental strains. Conclusions: These studies show that the method we have developed can accurately compute 3D displacement and segmented LV strain from 4D data.