Cytotoxic Terpenes from the Flowers of Inula japonica against Human Hepatocarcinoma Cells.

Two new 1,10-seco-eudesmanolides (1 and 2) were isolated from the flowers of Inula japonica together with two eudesmanolide analogs (3 and 4) and two monoterpene derivatives (5 and 6). Their structures were established on the basis of detailed spectroscopic analyses and electronic circular dichroism data. All isolates were evaluated for their antiproliferative activities against human hepatocarcinoma HepG2 and SMMC-7721 cells. Japonipene B (3) exhibited the most potent effect with the IC50 values of 14.60±1.62 and 22.06±1.34 µM against HepG2 and SMMC-7721 cells, respectively. Furthermore, japonipene B (3) showed significant efficacies of arresting the cell cycle at the S/G2-M stages, inducing mitochondria-mediated apoptosis, and inhibiting cell migration in HepG2 cells.

Sesquiterpenoids isolated from the flower of Inula japonica as potential antitumor leads for intervention of paclitaxel-resistant non-small-cell lung cancer.

Three new sesquiterpene lactone dimers (1-3) were isolated from the flowers of Inula japonica together with twenty-two known sesquiterpene derivatives (4-25). Their structures were established on the basis of detailed spectroscopic analyses. All isolates were evaluated for their antiproliferative activities against paclitaxel-resistant human non-small-cell lung cancer cell line A549/PTX. The preliminary structure-activity relationship was discussed. Compound 24 exhibited the most potent effect with the IC50 value of 0.34 ± 0.10 µM, even more active than the clinically used drug paclitaxel (PTX, IC50 = 1.40 ± 0.52 µM). Compound 24 showed significant efficacy of arresting the cell cycle at the G2-M stage, inducing apoptosis through mitochondria-mediated pathway, and inhibiting cell migration and invasion. Furthermore, compound 24 could reverse multidrug resistance through suppressing the expression of ABC family proteins.

Identification of Parthenolide Dimers as Activators of Pyruvate Kinase M2 in Xenografts of Glioblastoma Multiforme in Vivo.

Herein we detail the discovery of a series of parthenolide dimers as activators of PKM2 and evaluation of their anti-GBM activities. The most promising compound 5 showed high potency to activate PKM2 with an AC50 value of 15 nM, inhibited proliferation and metastasis, and induced apoptosis of GBM cells. Compound 5 could promote tetramer formation of PKM2 and reduce nucleus translocation of PKM2 in GBM cells without influence on the expression of total PKM2, thereby inhibiting the STAT3 signal pathway in vitro and in vivo. PKM2 knockdown assay demonstrated that the anti-GBM effect of 5 mainly depended on the expression of PKM2 in vitro and in vivo. Compound 16, a prodrug of 5, markedly suppressed U118 tumor xenograft growth and reduced the weight of tumor. On the basis of these investigations, we propose that 16 might be considered as a promising lead compound for discovery of anti-GBM drugs.

Sesquiterpenoids from the roots of Inula helenium inhibit acute myelogenous leukemia progenitor cells.

One new eudesmane sesquiterpenoid, 11ß-hydroxy-13-chloro-eudesm-5-en-12, 8-olide (1), was isolated from the roots of Inula helenium together with nine eudesmanolides (2-10) and one germacranolide (11). Their structures were elucidated on the basis of detailed spectroscopic analyses. All isolates were evaluated for their antiproliferative activities against human leukemia stem-like cell line KG1a. Compound 10 exhibited the most potent effect with the IC50 value of 3.36 ±â€¯0.18 µM. A further investigation revealed that compound 10 could significantly induce apoptosis of KG1a cells. Additionally, compound 10 had an obvious effect on the levels of apoptosis-related proteins (Bcl-2, Bax, cytochrome c, caspase 9 and caspase 3), indicating that the antiproliferative effect of compound 10 on KG1a cells might be mediated through a mitochondria-dependent apoptotic pathway.

Scan equalization digital radiography (SEDR) implemented with an amorphous selenium flat-panel detector: initial experience.

It is well recognized in projection radiography that low-contrast detectability suffers in heavily attenuating regions due to excessively low x-ray fluence to the image receptor and higher noise levels. Exposure equalization can improve image quality by increasing the x-ray exposure to heavily attenuating regions, resulting in a more uniform distribution of exposure to the detector. Image quality is also expected to be improved by using the slot-scan geometry to reject scattered radiation effectively without degrading primary x-rays. This paper describes the design of a prototype scan equalization digital radiography (SEDR) system implemented with an amorphous silicon (a-Si) thin-film transistor (TFT) array-based flat-panel detector. With this system, slot-scan geometry with alternate line erasure and readout (ALER) technique was used to achieve scatter rejection. A seven-segment beam height modulator assembly was mounted onto the fore collimator to regulate exposure regionally for chest radiography. The beam modulator assembly, consisting of micro linear motors, lead screw cartridge with lead (Pb) beam blockers attached, position feedback sensors and motor driver circuitry, has been tested and found to have an acceptable response for exposure equalization in chest radiography. An anthropomorphic chest phantom was imaged in the posterior-anterior (PA) view under clinical conditions. Scatter component, primary x-rays, scatter-to-primary ratios (SPRs) and primary signal-to-noise ratios (PSNRs) were measured in the SEDR images to evaluate the rejection and redistribution of scattered radiation, and compared with those for conventional full-field imaging with and without anti-scatter grid methods. SPR reduction ratios (SPRRRs, defined as the differences between the non-grid full-field SPRs and the reduced SPRs divided by the former) yielded approximately 59% for the full-field imaging with grid and 82% for the SEDR technique in the lungs, and 77% for the full-field imaging with grid and 95% for the SEDR technique in the subdiaphragm. The SEDR technique demonstrated a substantial improvement in PSNRs over the anti-scatter grid technique. The improvements of PSNRs varied with the regions and are more pronounced in heavily attenuating regions.

An Accurate Scatter Measurement and Correction Technique for Cone Beam Breast CT Imaging Using Scanning Sampled Measurement (SSM) Technique.

We developed and investigated a scanning sampled measurement (SSM) technique for scatter measurement and correction in cone beam breast CT imaging. A cylindrical polypropylene phantom (water equivalent) was mounted on a rotating table in a stationary gantry experimental cone beam breast CT imaging system. A 2-D array of lead beads, with the beads set apart about ~1 cm from each other and slightly tilted vertically, was placed between the object and x-ray source. A series of projection images were acquired as the phantom is rotated 1 degree per projection view and the lead beads array shifted vertically from one projection view to the next. A series of lead bars were also placed at the phantom edge to produce better scatter estimation across the phantom edges. Image signals in the lead beads/bars shadow were used to obtain sampled scatter measurements which were then interpolated to form an estimated scatter distribution across the projection images. The image data behind the lead bead/bar shadows were restored by interpolating image data from two adjacent projection views to form beam-block free projection images. The estimated scatter distribution was then subtracted from the corresponding restored projection image to obtain the scatter removed projection images.Our preliminary experiment has demonstrated that it is feasible to implement SSM technique for scatter estimation and correction for cone beam breast CT imaging. Scatter correction was successfully performed on all projection images using scatter distribution interpolated from SSM and restored projection image data. The resultant scatter corrected projection image data resulted in elevated CT number and largely reduced the cupping effects.