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Liu Y.,CAS Shanghai Institute of Applied Physics | Cheng D.,Fudan University | Cheng D.,Shanghai Institute of Medical Imaging | Ge M.,CAS Shanghai Institute of Applied Physics | Lin W.,CAS Shanghai Institute of Applied Physics
Chemical Biology and Drug Design | Year: 2016

In 80–90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K+ solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K+ is extremely controversial, this study provides information for the understanding of different G-quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K+ solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design. © 2016 John Wiley & Sons A/S

Cheng D.,Fudan University | Cheng D.,Shanghai Institute of Medical Imaging | Li X.,Fudan University | Li X.,Shanghai Institute of Medical Imaging | And 3 more authors.
Nanoscale Research Letters | Year: 2014

Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100 μg/mL rod-shaped MNPs (rMNP, length of 200 ± 50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200 ± 50 nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was also interesting to find that killing tumor cells at either higher (500 μg/mL) or lower (20 μg/mL) concentration of MNPs was less efficient than that achieved at 100 μg/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations. © 2014 Cheng et al.; licensee Springer.

Wang C.,Fudan University | Wang C.,Shanghai Institute of Medical Imaging | Ren R.,Fudan University | Hu H.,Fudan University | And 5 more authors.
Chinese Journal of Cancer Research | Year: 2014

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that repress their targets at post transcriptional level. Existing studies have shown that miRNAs are important regulatory genes in hepatocellular carcinoma (HCC), as either tumor suppressors or oncogenes. MiR-122 is normally downregulated in HCC and regarded as a tumor suppressor. Recently miR-122 has been reported to be regulated by CEBPA, which is then involved in a novel pathway to influence proliferation of tumor cells. However it is unknown whether CEBPA is regulated by miRNAs in HCC. In this study, we find that miR-182 is upregulated in HCC model rat, and represses CEBPA in both rat and human. This further improves the current CEBPA/miR-122 pathway that controls the proliferation of tumor cells. These results suggest that miR-182 is a potential oncogene in HCC and could be used as a diagnostic marker and drug target of HCC. © Chinese Journal of Cancer Research. All rights reserved.

Zhang Y.,Fudan University | Zhang Y.,Shanghai Institute of Medical Imaging | Shi H.,Fudan University | Shi H.,Shanghai Institute of Medical Imaging | And 6 more authors.
Nuclear Medicine Communications | Year: 2011

Purpose: The objective of this study was to compare the diagnostic value obtained using single-photon emission computed tomography (SPECT)/spiral computed tomography (CT) with Tc-99m methylene-diphosphonate with that obtained using SPECT alone in patients with spinal lesions. Methods: This was a retrospective study of 56 patients who underwent planar whole-body scintigraphy because of bone pain or osseous lesions that had been detected by other imaging techniques, or for the investigation of bone metastasis in patients with extraskeletal malignancies. Only patients who had hot spots detected in their spine and who had undergone single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were included. One lesion from each patient was resected or biopsied for pathological diagnosis, and lesions for which a pathological diagnosis could be made were included in this study. Single-photon emission computed tomography (SPECT) and SPECT/CT images were independently interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the study. The physicians were aware of patients' sex, age, history of histologically confirmed extraskeletal malignancy, and whole-body scintigraphy results, but were unaware of the results of other investigations, such as X-ray, MRI, and laboratory tests. SPECT images were analyzed first, followed by SPECT/CT images. Each lesion was graded on a 4-point diagnostic scale (1, benign; 2, likely benign; 3, likely malignant; 4, malignant), and the inter-reviewer agreement and the agreement of the SPECT and SPECT/CT diagnoses with the pathology results were evaluated by κ scores. Results: The pathology results revealed 39 malignant bone tumors and 17 benign lesions. In the malignant cases, 20 were bone metastases and 19 were malignant tumors of another histological type. The reviewers rated 67.9% of lesions as equivocal (grade 2-3) by SPECT, but only 19.6% as equivocal by SPECT/CT. The κ scores for inter-reviewer agreement were 0.467 for SPECT and 0.905 for SPECT/CT (both P<0.0001). The κ scores for the agreement of the interpretation of SPECT and SPECT/CT with the pathology results were 0.493 and 0.689, respectively (both P<0.0001). Conclusion: Compared with SPECT imaging, SPECT/spiral CT hybrid imaging significantly reduced the number of lesions judged to be equivocal. This reduction allowed for a definitive diagnosis to be made by imaging in the majority of patients. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Wu D.,Fudan University | Wu D.,Shanghai Institute of Medical Imaging | Tan M.,Fudan University | Tan M.,Shanghai Institute of Medical Imaging | And 10 more authors.
Investigative Radiology | Year: 2015

Objectives: Detecting microvascular invasion (mVI) in patients with hepatocellular carcinoma is a diagnostic challenge. The present study aimed to acquire a series of quantitative perfusion parameters from liver computed tomography (CT) with a 320-slice scanner in patients with small hepatocellular carcinoma (sHCC) and study its efficacy in identifying mVI. Materials and Methods: Fifty-six patients who underwent hepatic resection for sHCC (≤3 cm) were preoperatively examined with a 320-detector row CT scanner. Histopathological analyses of liver biopsies confirmed that 18 patients had sHCC with mVI and that 38 patients had sHCC without mVI. Hepatic artery flow, portal vein flow (PVF), and perfusion index were measured in both tumor and normal liver tissues. Nonparametric receiver operating characteristic curve analysis was performed to quantify the accuracy of the perfusion CT parameters. Results: The tumor PVF (PVFtumor), difference in PVF between tumor and liver tissue (ΔPVF), and the ΔPVF/liver PVF ratio (rPVF) were significantly higher in sHCC with mVI than in sHCC without mVI (P = 0.0094, P = 0.0018, and P = 0.0007, respectively; Wilcoxon signed rank test). The PVFtumor, ΔPVF, and rPVF correctly predicted mVI in 73.2% (sensitivity, 66.7%; specificity, 76.3%; cutoff, 103.8 mL per 100 mL/min), 76.8% (sensitivity, 66.7%; specificity, 81.6%; cutoff, -53.65 mLper 100mL/min), and 83.9%(sensitivity, 77.8%; specificity, 86.8%; cutoff, -0.38) of a total of 56 patients with sHCC, respectively. Other parameters were not significantly different between the groups. Conclusions: Liver CT perfusion provides a noninvasive, quantitative method that can predict mVI in patients with sHCC through measurement of 3 perfusion parameters: PVFtumor, ΔPVF, and rPVF. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

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