Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis.

BACKGROUND: Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA. METHODS: CHON-001 cells were treated with IL-1ß to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1ß-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1ß-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1ß-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1ß-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect. CONCLUSION: Circ_0044235 knockdown alleviated IL-1ß-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.

PixelPrint: A collection of three-dimensional printed CT phantoms of different respiratory diseases.

Imaging is often a first-line method for diagnostics and treatment. Radiological workflows increasingly mine medical images for quantifiable features. Variability in device/vendor, acquisition protocol, data processing, etc., can dramatically affect quantitative measures, including radiomics. We recently developed a method (PixelPrint) for 3D-printing lifelike computed tomography (CT) lung phantoms, paving the way for future diagnostic imaging standardization. PixelPrint generates phantoms with accurate attenuation profiles and textures by directly translating clinical images into printer instructions that control density on a voxel-by-voxel basis. The present study introduces a library of 3D printed lung phantoms covering a wide range of lung diseases, including usual interstitial pneumonia with advanced fibrosis, chronic hypersensitivity pneumonitis, secondary tuberculosis, cystic fibrosis, Kaposi sarcoma, and pulmonary edema. CT images of the patient-based phantom are qualitatively comparable to original CT images, both in texture, resolution and contrast levels allowing for clear visualization of even subtle imaging abnormalities. The variety of cases chosen for printing include both benign and malignant pathology causing a variety of alveolar and advanced interstitial abnormalities, both clearly visualized on the phantoms. A comparison of regions of interest revealed differences in attenuation below 6 HU. Identical features on the patient and the phantom have a high degree of geometrical correlation, with differences smaller than the intrinsic spatial resolution of the scans. Using PixelPrint, it is possible to generate CT phantoms that accurately represent different pulmonary diseases and their characteristic imaging features.

Supercritical fluid extract of Angelica sinensis promotes the anti-colorectal cancer effect of oxaliplatin.

Oxaliplatin-based chemotherapy regimens are recommended for patients with advanced colorectal cancer (CRC). However, oxaliplatin (OXA) can cause toxic side effects at the recommended dosage. Therefore, it is necessary to find new drug candidates that can synergize with OXA and thereby lower the OXA dose while still maintaining its efficacy. Angelica sinensis is a common drug in traditional Chinese medicine and has demonstrated a significant anti-CRC effect in modern pharmacological studies. The active ingredients in Angelica sinensis can be effectively extracted by a supercritical fluid extract. In this study, the supercritical fluid extract of Angelica sinensis (A-SFE) was obtained by a stable extraction process and was chemically characterized by GC/MS. The anti-cancer effect of A-SFE when applied individually was explored in vitro through MTT, scratch, and Transwell assay. The effect of A-SFE on CRC cells under the influence of tumor-associated macrophages (TAMs) was explored by a co-culture model. The results showed that A-SFE could inhibit the viability, metastasis, and invasion of HCT116 cells, especially under the influence of TAMs. When 20-100 µg/ml of A-SFE and 8-64 µg/ml of OXA were used in combination in HCT116 cells, synergistic or additive effects were shown in different concentration combinations. The CT26 syngeneic mouse model was used to explore the anti-CRC effect of OXA combined with A-SFE in vivo. The tumor volume, expression levels of Ki67, MMP9, and CD206 in the OXA + A-SFE group were less than those in the OXA group. In conclusion, A-SFE has the potential to become an adjuvant drug for OXA in the treatment of CRC, which provides new strategies for anti-colorectal cancer research.

miR-187/PDLIM1 Gets Involved in Gastric Cancer Progression and Cisplatin Sensitivity of Cisplatin by Mediating the Hippo-YAP Signaling Pathway.

Gastric cancer (GC) is one of the most prevalent malignancies in the digestive system across the world. The function and mechanism of PDLIM1, a cancer-suppressing gene, in gastric cancer progression remain unclear. This study is aimed at investigating the expression features and function of PDLIM1 in GC. RT-qPCR and western blot were used to compare the profiles of PDLIM1 and miR-187 between GC and normal tissues. The cell models of PDLIM1 overexpression and low expression were established in gastric cancer cell lines MKN45 and AGS. CCK8 and BrdU assays measured cell proliferation. Flow cytometry monitored cell apoptosis. Transwell analyzed cell invasion and migration. The influence of miR-187 overexpression on gastric cancer development was assessed. We predicted the targeted correlation between miR-187 and PDLIM1 through bioinformatics, which was corroborated via dual luciferase activity assay and RIP. Meanwhile, the cell model of PDLIM1 overexpression was built in AGS cells transfected with miR-187 mimics. A rescue experiment was conducted to assess the impact of PDLIM1 overexpression on the procancer function of miR-187. As a result, in contrast with normal paracancer tissues, PDLIM1 was substantially downregulated in GC tissues. Moreover, PDLIM1 overexpression considerably dampened proliferation, invasion, and migration in GC cells, boosted the cell apoptosis, and bolstered their sensitivity to cisplatin. PDLIM1 knockdown or miR-187 overexpression dramatically fostered GC cell proliferation, invasion, and migration and repressed cell apoptosis. Mechanism studies demonstrated that PDLIM1 vigorously restrained the profiles of the Hippo-YAP signaling pathway and the downstream target genes. miR-187 targeted PDLIM1, while miR-187 overexpression cramped PDLIM1 expression. The rescue experiment suggested that PDLIM1 overexpression weakened the procancer function of miR-187 in GC cells. In conclusion, our study demonstrated that PDLIM1 presented a low expression in GC tissues, while miR-187/PDLIM1 participated in GC development and cisplatin sensitivity by mediating the Hippo-YAP signaling pathway.

Diagnostic significance of CyclinD1 and D2-40 expression for follicular neoplasm of the thyroid.

OBJECTIVES: To evaluate the expression and differential diagnostic significance of CyclinD1 and D2-40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. METHODS: A total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2-40 was performed. RESULTS: We found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2-40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2-40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2-40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). CONCLUSIONS: CyclinD1 and D2-40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

In Vitro and In Vivo Studies on the Antibacterial Activity and Safety of a New Antimicrobial Peptide Dermaseptin-AC.

Antimicrobial resistance has been an increasing public health threat in recent years. Antimicrobial peptides are considered as potential drugs against drug-resistant bacteria because they are mainly broad-spectrum and are unlikely to cause resistance. In this study, a novel peptide was obtained from the skin secretion of Agalychnis callidryas using the "shotgun" cloning method. The amino acid sequence, molecular weight, and secondary structure of Dermaseptin-AC were determined. The in vitro antimicrobial activity, hemolysis, and cytotoxicity of Dermaseptin-AC were evaluated. MICs and minimum bactericidal concentrations (MBCs) of Dermaseptin-AC against seven different bacterial strains ranged between 2 ∼ 4 µM and 2 ∼ 8 µM. The HC50 (50% maximum hemolysis concentration) of Dermaseptin-AC against horse erythrocytes was 76.55 µM. The in vivo anti-MRSA effect was tested on immune-suppressed MRSA pneumonia in mice. Dermaseptin-AC showed anti-MRSA effects similar to the same dose of vancomycin (10 mg/kg body weight). Short-term (7 days of intraperitoneal injection, 10 mg/kg body weight) in vivo safety evaluation of Dermaseptin-AC was tested on mice. The survival rate during the 7-day injection was 80%. Dermaseptin-AC showed no obvious effect on the liver, heart, spleen, kidney, and blood, but did induce slight pulmonary congestion. The skin safety of Dermaseptin-AC was evaluated on wounds on the back skin of a rat, and no irritation was observed. IMPORTANCE In this study, we discovered a new antimicrobial peptide, Dermaseptin-AC, and studied its in vitro and in vivo antimicrobial activity. These studies provide some data for finding new antimicrobial peptides for overcoming antimicrobial resistance. Dermaseptin-AC showed strong broad-spectrum antibacterial activity and relatively low hemolysis, and was more cytotoxic to cancer cells than to normal cells. Dermaseptin-AC was active in vivo, and its anti-MRSA effect was similar to that of vancomycin when administered by intraperitoneal injection. Safety studies found that continuous injection of Dermaseptin-AC may cause mild pulmonary congestion, while there was no obvious irritation when it was applied to skin wounds. Chronic wounds are often accompanied by high bacterial burdens and, at the same time, antimicrobial resistance is more likely to occur during repeated infections and treatments. Therefore, developing Dermaseptin-AC to treat chronic wound infection may be an attractive choice.

Low-dose MDCT: evaluation of the impact of systematic tube current reduction and sparse sampling on quantitative paraspinal muscle assessment.

BACKGROUND: Wasting disease entities like cachexia or sarcopenia are associated with a decreasing muscle mass and changing muscle composition. For valid and reliable disease detection and monitoring diagnostic techniques offering quantitative musculature assessment are needed. Multi-detector computed tomography (MDCT) is a broadly available imaging modality allowing for muscle composition analysis. A major disadvantage of using MDCT for muscle composition assessment is the radiation exposure. In this study we evaluated the performance of different methods of radiation dose reduction for paravertebral muscle composition assessment. METHODS: MDCT scans of eighteen subjects (6 males, age: 71.5±15.9 years, and 12 females, age: 71.0±8.9 years) were retrospectively simulated as if they were acquired at 50%, 10%, 5%, and 3% of the original X-ray tube current or number of projections (i.e., sparse sampling). Images were reconstructed with a statistical iterative reconstruction (SIR) algorithm. Paraspinal muscles (psoas and erector spinae muscles) at the level of L4 were segmented in the original-dose images. Segmentations were superimposed on all low-dose scans and muscle density (MD) extracted. RESULTS: Sparse sampling derived mean MD showed no significant changes (P=0.57 and P=0.22) down to 5% of the original projections in the erector spinae and psoas muscles, respectively. All virtually reduced tube current series showed significantly different (P>0.05) mean MD in the psoas and erector spinae muscles as compared to the original dose except for the images of 5% of the original tube current in the erector spinae muscle. CONCLUSIONS: Our findings demonstrated the possibility of considerable radiation dose reduction using MDCT scans for assessing the composition of the paravertebral musculature. The sparse sampling approach seems to be promising and a potentially superior technique for dose reduction as compared to tube current reduction.

Spectral CT quantification stability and accuracy for pediatric patients: A phantom study.

BACKGROUND: Spectral computed tomography (spectral CT) provides access to clinically relevant measures of endogenous and exogenous materials in patients. For pediatric patients, current spectral CT applications include lesion characterization, quantitative vascular imaging, assessments of tumor response to treatment, and more. OBJECTIVE: The aim of this study is a comprehensive investigation of the accuracy and stability of spectral quantifications from a spectral detector-based CT system with respect to different patient sizes and radiation dose levels relevant for the pediatric population. MATERIALS AND METHODS: A spectral CT phantom with tissue-mimicking materials and iodine concentrations relevant for pediatric imaging was scanned on a spectral detector CT system using a standard pediatric abdominal protocol at 100%, 67%, 33% and 10% of the nominal radiation dose level. Different pediatric patient sizes were simulated using supplemental 3D-printed extension rings. Virtual mono-energetic, iodine density, effective atomic number, and electron density results were analyzed for stability with respect to radiation dose and patient size. RESULTS: Compared to conventional CT imaging, a pronounced improvement in the stability of attenuation measurements across patient size was observed when using virtual mono-energetic images. Iodine densities were within 0.1 mg/ml, effective atomic numbers were within 0.26 atomic numbers and electron density quantifications were within ±1.0% of their respective nominal values. Relative to the nominal dose clinical protocol, differences in attenuation of all tissue-mimicking materials were maintained below 1.6 HU for a 33% dose reduction, below 2.7 HU for a 67% dose reduction and below 3.7 HU for a 90% dose reduction, for all virtual mono-energetic energies equal to or greater than 50 keV. Iodine, and effective atomic number quantifications were stable to within 0.1 mg/ml and 0.06 atomic numbers, respectively, across all measured dose levels. CONCLUSION: Spectral CT provides accurate and stable material quantification with respect to radiation dose reduction (up to 90%) and differing pediatric patient size. The observed consistency is an important step towards quantitative pediatric imaging at low radiation exposure levels.

Opportunistic osteoporosis screening: contrast-enhanced dual-layer spectral CT provides accurate measurements of vertebral bone mineral density.

OBJECTIVES: Osteoporosis remains under-diagnosed, which may be improved by opportunistic bone mineral density (BMD) measurements on CT. However, correcting for the influence of intravenous iodine-based contrast agent is challenging. The purpose of this study was to assess the diagnostic accuracy of iodine-corrected vertebral BMD measurements derived from non-dedicated contrast-enhanced phantomless dual-layer spectral CT (DLCT) examinations. METHODS: Vertebral volumetric DLCT-BMD was measured in native, arterial, and portal-venous scans of 132 patients (63 ± 16 years; 32% women) using virtual monoenergetic images (50 and 200 keV). For comparison, conventional BMD was determined using an asynchronous QCT calibration. Additionally, iodine densities were measured in the abdominal aorta (AA), inferior vena cava, and vena portae (VP) on each CT phase to adjust for iodine-related measurement errors in multivariable linear regressions and a generalized estimated equation, and conversion equations were calculated. RESULTS: BMD values derived from contrast-enhanced phases using conversion equations adjusted for individual vessel iodine concentrations of VP and/or AA showed a high agreement with those from non-enhanced scans in Bland-Altman plots. Mean absolute errors (MAE) of DLCT-BMD were 3.57 mg/ml for the arterial (R2 = 0.989) and 3.69 mg/ml for the portal-venous phase (R2 = 0.987) (conventional BMD: 4.70 [R2 = 0.983] and 5.15 mg/ml [R2 = 0.981]). In the phase-independent analysis, MAE was 4.49 mg/ml for DLCT (R2 = 0.989) (conventional BMD: 4.82 mg/ml [R2 = 0.981]). CONCLUSIONS: Converted BMD derived from contrast-enhanced DLCT examinations and adjusted for individual vessel iodine concentrations showed a high agreement with non-enhanced DLCT-BMD, suggesting that opportunistic BMD measurements are feasible even in non-dedicated contrast-enhanced DLCT examinations. KEY POINTS: • Accurate BMD values can be converted from contrast-enhanced DLCT scans, independent from the used scan phase. • DLCT-BMD measurements from contrast-enhanced scans should be adjusted with iodine concentrations of portal vein and/or abdominal aorta, which significantly improves the goodness-of-fit of conversion models.

Bone mineral density measurements derived from dual-layer spectral CT enable opportunistic screening for osteoporosis.

OBJECTIVE: To investigate the in vivo applicability of non-contrast-enhanced hydroxyapatite (HA)-specific bone mineral density (BMD) measurements based on dual-layer CT (DLCT). METHODS: A spine phantom containing three artificial vertebral bodies with known HA densities was measured to obtain spectral data using DLCT and quantitative CT (QCT), simulating different patient positions and grades of obesity. BMD was calculated from virtual monoenergetic images at 50 and 200 keV. HA-specific BMD values of 174 vertebrae in 33 patients (66 ± 18 years; 33% women) were determined in non-contrast routine DLCT and compared with corresponding QCT-based BMD values. RESULTS: Examining the phantom, HA-specific BMD measurements were on a par with QCT measurements. In vivo measurements revealed strong correlations between DLCT and QCT (r = 0.987 [95% confidence interval, 0.963-1.000]; p < 0.001) and substantial agreement in a Bland-Altman plot. CONCLUSION: DLCT-based HA-specific BMD measurements were comparable with QCT measurements in in vivo analyses. This suggests that opportunistic DLCT-based BMD measurements are an alternative to QCT, without requiring phantoms and specific protocols. KEY POINTS: • DLCT-based hydroxyapatite-specific BMD measurements show a substantial agreement with QCT-based BMD measurements in vivo. • DLCT-based hydroxyapatite-specific measurements are on a par with QCT in spine phantom measurements. • Opportunistic DLCT-based BMD measurements may be a feasible alternative for QCT, without requiring dedicated examination protocols or a phantom.

Dual-layer spectral computed tomography: measuring relative electron density.

BACKGROUND: X-ray and particle radiation therapy planning requires accurate estimation of local electron density within the patient body to calculate dose delivery to tumour regions. We evaluate the feasibility and accuracy of electron density measurement using dual-layer computed tomography (DLCT), a recently introduced dual-energy CT technique. METHODS: Two calibration phantoms were scanned with DLCT and virtual monoenergetic images (VMIs) at 50 keV and 200 keV were generated. We investigated two approaches to obtain relative electron densities from these VMIs: to fit an analytic interaction cross-sectional model and to empirically calibrate a conversion function with one of the phantoms. Knowledge of the emitted x-ray spectrum was not required for the presented work. RESULTS: The results from both methods were highly correlated to the nominal values (R > 0.999). Except for the water and lung inserts, the error was within 1.79% (average 1.53%) for the cross-sectional model and 1.61% (average 0.87%) for the calibrated conversion. Different radiation doses did not have a significant influence on the measurement (p = 0.348, 0.167), suggesting that the methods are reproducible. Further, we applied these methods to routine clinical data. CONCLUSIONS: Our study shows a high validity of electron density estimation based on DLCT, which has potential to improve the procedure and accuracy of measuring electron density in clinical practice.

Three-material decomposition with dual-layer spectral CT compared to MRI for the detection of bone marrow edema in patients with acute vertebral fractures.

OBJECTIVES: To assess whether bone marrow edema in patients with acute vertebral fractures can be accurately diagnosed based on three-material decomposition with dual-layer spectral CT (DLCT). MATERIALS AND METHODS: Acute (n = 41) and chronic (n = 18) osteoporotic thoracolumbar vertebral fractures as diagnosed by MRI (hyperintense signal in STIR sequences) in 27 subjects (72 ± 11 years; 17 women) were assessed with DLCT. Spectral data were decomposed into hydroxyapatite, edema-equivalent, and fat-equivalent density maps using an in-house-developed algorithm. Two radiologists, blinded to clinical and MR findings, assessed DLCT and conventional CT independently, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). For DLCT and conventional CT, accuracy, sensitivity, and specificity for identifying acute fractures (Likert scale, 3 and 4) were analyzed separately using MRI as standard of reference. RESULTS: For the identification of acute fractures, conventional CT showed a sensitivity of 0.73-0.76 and specificity of 0.78-0.83, whereas the sensitivity (0.93-0.95) and specificity (0.89) of decomposed DLCT images were substantially higher. Accuracy increased from 0.76 for conventional CT to 0.92-0.93 using DLCT. Interreader agreement for fracture assessment was high in conventional CT (weighted κ [95% confidence interval]; 0.81 [0.70; 0.92]) and DLCT (0.96 [0.92; 1.00]). CONCLUSIONS: Material decomposition of DLCT data substantially improved accuracy for the diagnosis of acute vertebral fractures, with a high interreader agreement. This may spare patients additional examinations and facilitate the diagnosis of vertebral fractures.

Effect of radiation dose reduction on texture measures of trabecular bone microstructure: an in vitro study.

Osteoporosis is characterized by bone loss and degradation of bone microstructure leading to fracture particularly in elderly people. Osteoporotic bone degeneration and fracture risk can be assessed by bone mineral density and trabecular bone score from 2D projection dual-energy X-ray absorptiometry images. However, multidetector computed tomography image based quantification of trabecular bone microstructure showed significant improvement in prediction of fracture risk beyond that from bone mineral density and trabecular bone score; however, high radiation exposure limits its use in routine clinical in vivo examinations. Hence, this study investigated reduction of radiation dose and its effects on image quality of thoracic midvertebral specimens. Twenty-four texture features were extracted to quantify the image quality from multidetector computed tomography images of 11 thoracic midvertebral specimens, by means of statistical moments, the gray-level co-occurrence matrix, and the gray-level run-length matrix, and were analyzed by an independent sample t-test to observe differences in image texture with respect to radiation doses of 80, 150, 220, and 500 mAs. The results showed that three features-namely, global variance, energy, and run percentage, were not statistically significant ([Formula: see text]) for low doses with respect to 500 mAs. Hence, it is evident that these three dose-independent features can be used for disease monitoring with a low-dose imaging protocol.

Modified Leukocyte Filter Removes Tumor Cells from the Salvaged Blood.

BACKGROUND: Intraoperative blood salvage, an effective blood conservation strategy, has not been applied in onco-surgery, because of potential malignant cell contamination. In this study we tested effectiveness of a modified leukocyte depletion filter (M-LDF) for removal of tumor cells. MATERIALS AND METHODS: The effects of M-LDF and regular LDF on removal of cells (HepG2 cell line) were compared. The safety of M-LDF was tested with blood (collected and washed during onco-surgery), the salvaged blood mixed with tumor cells from the solid tumor of the same patient, or mixed with HepG2 cells (n=30 in each protocol). Cancer cells were identified by flow cytometry, culture and bioassay with and without filtration. RESULTS: M-LDF removed 5-log of HepG2 and nucleated cells, which was much higher than regular LDF, and cells were destroyed when they passed through M-LDF. Cytokeratin-positive cells in all samples were removed by M-LDF. Invasive growth adherent cells were found in most of unfiltered samples and 67% of the inoculated nude mice developed tumors in LDF-treated sample. Neither adherent cells nor nude mice developed tumors were found in M-LDF-treated samples. DISCUSSION AND CONCLUSION: Since M-LDF can effectively remove and destroy cancer cells in the salvaged blood, it has great potential for clinical application.

A comparison of material decomposition techniques for dual-energy CT colonography.

In recent years, dual-energy computed tomography (DECT) has been widely used in the clinical routine due to improved diagnostics capability from additional spectral information. One promising application for DECT is CT colonography (CTC) in combination with computer-aided diagnosis (CAD) for detection of lesions and polyps. While CAD has demonstrated in the past that it is able to detect small polyps, its performance is highly dependent on the quality of the input data. The presence of artifacts such as beam-hardening and noise in ultra-low-dose CTC may severely degrade detection performances of small polyps. In this work, we investigate and compare virtual monochromatic images, generated by image-based decomposition and projection-based decomposition, with respect to CAD performance. In the image-based method, reconstructed images are firstly decomposed into water and iodine before the virtual monochromatic images are calculated. On the contrary, in the projection-based method, the projection data are first decomposed before calculation of virtual monochromatic projection and reconstruction. Both material decomposition methods are evaluated with regards to the accuracy of iodine detection. Further, the performance of the virtual monochromatic images is qualitatively and quantitatively assessed. Preliminary results show that the projection-based method does not only have a more accurate detection of iodine, but also delivers virtual monochromatic images with reduced beam hardening artifacts in comparison with the image-based method. With regards to the CAD performance, the projection-based method yields an improved detection performance of polyps in comparison with that of the image-based method.

Myeloid sarcoma of the cheek and the maxillary sinus regions.

Myeloid sarcoma (MS) is a rare, extramedullary malignant tumor composed of immature myeloid precursor cells and myeloblast. Most MSs occur in the subperiosteal region of the bone, with the skull, sternum, ribs, and proximal portions of the long bones being the common sites of involvement. It is thought that the MS tumor originates in the bone marrow, and traverses the Haversian canals to reach the subperiosteum. Various reports have also described the involvement of the liver, spleen, brain, heart, pharynx, uterus, vagina, skin, kidney, and other soft tissues in the formation of the tumor.

A randomized phase II study of recombinant human endostatin plus gemcitabine/cisplatin compared with gemcitabine/cisplatin alone as first-line therapy in advanced non-small-cell lung cancer.

PURPOSE: Studies indicate that recombinant human endostatin (rh-endostatin) can inhibit tumor endothelial cell proliferation, angiogenesis, and tumor growth. This study assessed the efficacy of the combination of standard gemcitabine plus cisplatin chemotherapy with rh-endostatin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly (1:1) assigned to receive gemcitabine/cisplatin chemotherapy alone or with 7.5 mg/ m(2) of intravenously rh-endostatin on days 1 to 14 of each 3-week cycle. The primary end point was objective response rate (ORR). RESULTS: Baseline characteristics were similar between treatment arms. The best ORRs for rh-endostatin arm (n = 33) and chemotherapy-alone arm were 37.5% (95% CI: 21.3 to 47.2%) and 28.6% (95% CI: 19.8 to 37.6%), respectively. Median survival was 12.4 months in the rh-endostatin arm and 9.8 months in the chemotherapy-alone arm, and 1-year survival was 51.6% and 38.7%, respectively. Mild palpitions, diarrhea, and liver dysfunction were the most common rh-endostatin-related adverse events. Grade 3/4 hematological toxicities were all reported similar for patients in the two arms. CONCLUSION: The addition of rh-endostatin to gemcitabine plus cisplatin chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival.

Gene therapy with recombinant adenovirus encoding endostatin encapsulated in cationic liposome in coxsackievirus and adenovirus receptor-deficient colon carcinoma murine models.

Adenovirus (Ad)-based antiangiogenesis gene therapy is a promising approach for cancer treatment. Downregulation or loss of coxsackievirus and adenovirus receptor (CAR) is often detected in various human cancers, which hampers adenoviral gene therapy approaches. Cationic liposome-complexed adenoviral vectors have been proven useful in CAR-deficient cells to enhance therapeutic gene transfer in vivo. Here, we investigated the antitumor effects of recombinant adenovirus encoding endostatin (Ad-hE) encapsulated in cationic liposome (Ad-hE/Lipo) on CAR-deficient CT26 colon carcinoma murine models. In vitro, Ad-hE/Lipo enhanced adenovirus transfection in CAR-deficient cells (CT26), and endostatin gene expression was measured by both qualitative and quantitative detection. In addition, an antibody neutralizing assay indicated that neutralizing serum inhibited naked adenovirus 5 (Ad5) at rather higher dilution than the complexes of Ad5 and cationic liposomes (Ad5-CL), which demonstrated that Ad5-CL was more capable of protecting Ad5 from neutralization. In vivo, Ad-hE/Lipo treatment in the murine CT26 tumor model by intratumoral injection resulted in marked suppression of tumor growth and prolonged survival time, which was associated with a decreased number of microvessels and increased apoptosis of tumor cells. In conclusion, recombinant endostatin adenovirus encapsulated with cationic liposome effectively inhibited CAR-deficient tumor growth through an antiangiogenic mechanism in murine models without marked toxicity, thus showing a feasible strategy for clinical applications.

[Clinicopathologic study of 963 cases of mature T-cell and natural killer/T-cell lymphoma with respect to 2008 WHO classification of lymphoid neoplasms].

OBJECTIVE: To study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms. METHODS: Eleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms. RESULTS: Nine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly. CONCLUSIONS: Extranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.