circMYC promotes cell proliferation, metastasis, and glycolysis in cervical cancer by up-regulating MET and sponging miR-577.

OBJECTIVE: To analyze the role of circMYC in cervical cancer. METHODS: Protein and RNA expression was detected by RT-qPCR and western blotting. Transwell, CCK8, and colony formation assays were used for measuring metastasis, cell viability, and proliferation, respectively. Lactate production, glucose uptake, and ATP generation were examined to evaluate cell glycolysis. Interactions between circMYC, miR-577, and MET were determined by RNA pull-down and immunoprecipitation, and dual-luciferase reporter assays. Xenografts were established in mice to evaluate the functions of circMYC in vivo. RESULTS: circMYC was overexpressed in tumor tissue, which was related to poor prognosis. CircMYC knockdown reduced proliferation, colony formation, metastasis, and glycolysis in cervical cancer cells as well as inhibiting tumor growth in vivo. Mechanistically, circMYC targeted miR-577, and the effects of circMYC knockdown could be reversed by miR-577 inhibition. Moreover, miR-577 downregulated the expression of MET. Therefore, the oncogenic role of circMYC in cervical cancer was achieved by sponging miR-577 and maintaining MET expression. CONCLUSION: circMYC promotes cervical cancer progression through regulation of the miR-577/MET axis. circMYC may thus be a potential target for diagnosing and treating cervical cancer.

Thoracic Organ Doses and Cancer Risk from Low Pitch Helical 4-Dimensional Computed Tomography Scans.

PURPOSE: To investigate the dose depositions to organs at risk (OARs) and associated cancer risk in cancer patients scanned with 4-dimensional computed tomography (4DCT) as compared with conventional 3DCT. METHODS AND MATERIALS: The radiotherapy treatment planning CT image and structure sets of 102 patients were converted to CT phantoms. The effective diameters of those patients were computed. Thoracic scan protocols in 4DCT and 3DCT were simulated and verified with a validated Monte Carlo code. The doses to OARs (heart, lungs, esophagus, trachea, spinal cord, and skin) were calculated and their correlations with patient effective diameter were investigated. The associated cancer risk was calculated using the published models in BEIR VII reports. RESULTS: The average of mean dose to thoracic organs was in the range of 7.82-11.84 cGy per 4DCT scan and 0.64-0.85 cGy per 3DCT scan. The average dose delivered per 4DCT scan was 12.8-fold higher than that of 3DCT scan. The organ dose was linearly decreased as the function of patients' effective diameter. The ranges of intercept and slope of the linear function were 17.17-30.95 and -0.0278--0.0576 among patients' 4DCT scans, and 1.63-2.43 and -0.003--0.0045 among patients' 3DCT scans. Relative risk of cancer increased (with a ratio of 15.68:1) resulting from 4DCT scans as compared to 3DCT scans. CONCLUSIONS: As compared to 3DCT, 4DCT scans deliver more organ doses, especially for pediatric patients. Substantial increase in lung cancer risk is associated with higher radiation dose from 4DCT and smaller patients' size as well as younger age.

A measurement-based generalized source model for Monte Carlo dose simulations of CT scans.

The goal of this study is to develop a generalized source model for accurate Monte Carlo dose simulations of CT scans based solely on the measurement data without a priori knowledge of scanner specifications. The proposed generalized source model consists of an extended circular source located at x-ray target level with its energy spectrum, source distribution and fluence distribution derived from a set of measurement data conveniently available in the clinic. Specifically, the central axis percent depth dose (PDD) curves measured in water and the cone output factors measured in air were used to derive the energy spectrum and the source distribution respectively with a Levenberg-Marquardt algorithm. The in-air film measurement of fan-beam dose profiles at fixed gantry was back-projected to generate the fluence distribution of the source model. A benchmarked Monte Carlo user code was used to simulate the dose distributions in water with the developed source model as beam input. The feasibility and accuracy of the proposed source model was tested on a GE LightSpeed and a Philips Brilliance Big Bore multi-detector CT (MDCT) scanners available in our clinic. In general, the Monte Carlo simulations of the PDDs in water and dose profiles along lateral and longitudinal directions agreed with the measurements within 4%/1 mm for both CT scanners. The absolute dose comparison using two CTDI phantoms (16 cm and 32 cm in diameters) indicated a better than 5% agreement between the Monte Carlo-simulated and the ion chamber-measured doses at a variety of locations for the two scanners. Overall, this study demonstrated that a generalized source model can be constructed based only on a set of measurement data and used for accurate Monte Carlo dose simulations of patients' CT scans, which would facilitate patient-specific CT organ dose estimation and cancer risk management in the diagnostic and therapeutic radiology.

Size effect of Au/PAMAM contrast agent on CT imaging of reticuloendothelial system and tumor tissue.

Polyamidoamine (PAMAM)-entrapped Au nanoparticles were synthesized with distinct sizes to figure out the size effect of Au-based contrast agent on CT imaging of passively targeted tissues. Au/PAMAM nanoparticles were first synthesized with narrow distribution of particles size of 22.2 ± 3.1, 54.2 ± 3.7, and 104.9 ± 4.7 nm in diameters. Size effect leads no significant difference on X-ray attenuation when Au/PAMAM was ≤0.05 mol/L. For CT imaging of a tumor model, small Au/PAMAM were more easily internalized via endocytosis in the liver, leading to more obviously enhanced contrast. Similarly, contrast agents with small sizes were more effective in tumor imaging because of the enhanced permeability and retention effect. Overall, the particle size of Au/PAMAM heavily affected the efficiency of CT enhancement in imaging RES and tumors.

Predictive value of mutant p53 expression index obtained from nonenhanced computed tomography measurements for assessing invasiveness of ground-glass opacity nodules.

PURPOSE: To predict p53 expression index (p53-EI) based on measurements from computed tomography (CT) for preoperatively assessing pathologies of nodular ground-glass opacities (nGGOs). METHODS: Information of 176 cases with nGGOs on high-resolution CT that were pathologically confirmed adenocarcinoma was collected. Diameters, total volumes (TVs), maximum (MAX), average (AVG), and standard deviation (STD) of CT attenuations within nGGOs were measured. p53-EI was evaluated through immunohistochemistry with Image-Pro Plus 6.0. A multiple linear stepwise regression model was established to calculate p53-EI prediction from CT measurements. Receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of variables in differentiating preinvasive adenocarcinoma (PIA), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). RESULTS: Diameters, TVs, MAX, AVG, and STD showed significant differences among PIAs, MIAs, and IACs (all P-values <0.001), with only MAX being incapable to differentiate MIAs from IACs (P=0.106). The mean p53-EIs of PIAs, MIAs, and IACs were 3.4±2.0, 7.2±1.9, and 9.8±2.7, with significant intergroup differences (all P-values <0.001). An equation was established by multiple linear regression as: p53-EI prediction =0.001* TVs +0.012* AVG +0.022* STD +9.345, through which p53-EI predictions were calculated to be 4.4%±1.0%, 6.8%±1.3%, and 8.5%±1.4% for PIAs, MIAs, and IACs (Kruskal-Wallis test P<0.001; Tamhane's T2 test: PIA vs MIA P<0.001, MIA vs IAC P<0.001), respectively. Although not significant, p53-EI prediction has a little higher area under the curve (AUC) than the actual one both in differentiating MIAs from PIAs (AUC 0.938 vs 0.914, P=0.263) and in distinguishing IACs from MIAs (AUC 0.812 vs 0.786, P=0.718). CONCLUSION: p53-EI prediction of nGGOs obtained from CT measurements allows accurately estimating lesions' pathology and invasiveness preoperatively not only from radiology but also from pathology.

High-efficiency electrophosphorescent copolymers containing charged iridium complexes in the side chains.

A convenient approach to novel charged Ir polymers for optoelectronic devices to achieve red emission was developed. 2-(Pyridin-2-yl)benzimidazole units grafted into the side chains of macroligands (PFCz and PFP) served as ligands for the formation of charged Ir complex pendants with 1-phenylisoquinoline (1-piq). The charged Ir polymers (PFPIrPiq and PFCzIrPiq) showed exclusive Ir(1-piq)(2){N-[2-(pyridin-2-yl)benzimidazole]hexyl}(+)BF(4)(-) (IrPiq) emission, with the peak at 595 nm. The best device performances were obtained from PFCzIrPiq4 with the device configuration of ITO/PEDOT:PSS/PFCzIrPiq4+PBD (30 wt %)/TPBI/Ba/Al (PBD: 5-(4-tert-butylphenyl)-2-(biphenyl-4-yl)-1,3,4-oxadiazole; TPBI: 1,3,5-tris-(2-N-phenylbenzimidazolyl)benzene). A maximum external quantum efficiency (EQE) of 7.3 % and a luminous efficiency (LE) of 6.9 cd A(-1) with a luminance of 138 cd m(-2) were achieved at a current density of 1.9 mA cm(-2). The efficiencies remained as high as EQE=3.4 % and LE=3.3 cd A(-1) with a luminance of 3770 cd m(-2) at a current density of 115 mA cm(-2). The single-layer devices based on charged Ir polymers also showed high efficiency with the high work-function metal Ag as cathode. The maximum external quantum efficiencies of the devices were 0.64 % and 0.66 % for PFPIrPiq2 and PFPIrPiq10, respectively. A possible mechanism of an electrochemical cell associated with its electrochemical redox pathway for single-layer devices has been proposed. The results showed that the charged Ir polymers are promising candidate materials for polymer optoelectronic devices.