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授权专利(12项目):
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2013  (8 / Total 98 )

  • 1
    Wu J, Wang C, Li S, Li S, Wang W, Li J, Chi Y, Yang H, Kong X, Zhou Y, Dong C, Wang F, Xu G, Yang J, Gustafsson JA, Guan Y. Thyroid hormone-responsive SPOT 14 homolog promotes hepatic lipogenesis, and its expression is regulated by liver X receptor alpha through a sterol regulatory element-binding protein 1c-dependent mechanism in mice. Hepatology. 2013;58:617-628.

    Abstract

    The protein, thyroid hormone-responsive SPOT 14 homolog (Thrsp), has been reported to be a lipogenic gene in cultured hepatocytes, implicating an important role of Thrsp in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Thrsp expression is known to be regulated by a variety of transcription factors, including thyroid hormone receptor, pregnane X receptor, and constitutive androstane receptor. Emerging in vitro evidence also points to a critical role of liver X receptor (LXR) in regulating Thrsp transcription in hepatocytes. In the present study, we showed that Thrsp was up-regulated in livers of db/db mice and high-fat-diet-fed mice, two models of murine NAFLD. Hepatic overexpression of Thrsp increased triglyceride accumulation with enhanced lipogenesis in livers of C57Bl/6 mice, whereas hepatic Thrsp gene silencing attenuated the fatty liver phenotype in db/db mice. LXR activator TO901317 induced Thrsp expression in livers of wild-type (WT) and LXR-β gene-deficient mice, but not in LXR-α or LXR-α/β double-knockout mice. TO901317 treatment significantly enhanced hepatic sterol regulatory element-binding protein 1c (SREBP-1c) expression and activity in WT mice, but failed to induce Thrsp expression in SREBP-1c gene-deficient mice. Sequence analysis revealed four LXR response-element-like elements and one sterol regulatory element (SRE)-binding site within a -2,468 ∼+1-base-pair region of the Thrsp promoter. TO901317 treatment and LXR-α overexpression failed to induce, whereas overexpression of SREBP-1c significantly increased Thrsp promoter activity. Moreover, deletion of the SRE site completely abolished SREBP-1c-induced Thrsp transcription.

    CONCLUSION:

    Thrsp is a lipogenic gene in the liver that is induced by the LXR agonist through an LXR-α-mediated, SREBP-1c-dependent mechanism. Therefore, Thrsp may represent a potential therapeutic target for the treatment of NAFLD.

    http://dx.doi.org/10.1002/hep.26272

  • 2
    Wu H, Chen H, Sun Y, Wan Y, Wang F, Jia B, Su X. Imaging integrin alpha(v)beta(3) positive glioma with a novel RGD dimer probe and the impact of antiangiogenic agent (Endostar) on its tumor uptake. Cancer Lett. 2013;335:75-80.

    Abstract

    Integrin αvβ3 has been recognized to play an important role in angiogenesistumor growth and metastasis. It will be of interest to apply this promising target for tumor imaging and visualization of tumor angiogenesis in vivo. In this study, a novel integrin αvβ3 targetting imaging probe, (99m)Tc-HYNIC-E[c(RGDfK)]2, was used to investigate the glioma uptake in vitro and in vivo before and after treatment with an antiangiogenic agentendostar. The results indicated that U87MG glioma cells have high expression of integrin αvβ3 and special uptake of (99m)Tc-HYNIC-E[c(RGDfK)]2 both in cell line and in tumor xenograft. The endostatin analogue endostar can inhibit the expression of integrin αvβ3 receptors in both U87MG cells in vitro and gliomatissues, which suggested that integrin pathway may play a role in antiangiogenic effect of Endostar. (99m)Tc-HYNIC-E[c(RGDfK)]2 may be a promising molecular imaging probe for integrin αvβ3 positive tumor imaging and open up the possibility to establish an molecular imaging modality for assessment of tomor antiangiogenic therapy.

    http://linkinghub.elsevier.com/retrieve/pii/S0304-3835(13)00111-0

  • 3
    Shi J, Cui L, Jia B, Liu Z, He P, Dong C, Jin X, Zhao H, Li F, Wang F. Technetium 99m-labeled VQ peptide: a new imaging agent for the early detection of tumors or premalignancies. Mol Imaging. 2013;12:318-326.

    Abstract

    There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m (99mTc)-labeled VQ peptide (99mTc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99mTc-HYNIC-VQ was prepared by a non-SnCl2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99mTc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers.


  • 4
    Liu Z. Editorial. Molecular image-guided cancer treatment: moving towards personalized medicine--Part I. Curr Pharm Biotechnol. 2013;14:643.
  • 5
    Hou Y, Qiao R, Fang F, Wang X, Dong C, Liu K, Liu C, Liu Z, Lei H, Wang F, Gao M. NaGdF4 nanoparticle-based molecular probes for magnetic resonance imaging of intraperitoneal tumor xenografts in vivo. ACS Nano. 2013;7:330-338.

    Abstract

    Differently sized NaGdF(4) nanocrystals with narrow particle size distributions were synthesized by a high temperature approach. Upon ligand exchange, the as-prepared hydrophobic NaGdF(4) nanocrystals were transferred into water by using asymmetric PEGs simultaneously bearing phosphate and maleimide groups. Further investigations demonstrated that the water-soluble NaGdF(4) nanocrystals, coated by PEG bearing two phosphate groups on the same side, exhibit not only excellent colloidal stability in water and PBS buffer, but also higher T1 relaxivity than Gd-DTPA (Magnevist). Through "click" reaction between the maleimide residue on particle surface and thiol group from the partly reduced anti-EGFR monoclonal antibody (mAb), NaGdF(4)-PEG-mAb nanoprobes were constructed, and their biocompatibility and binding specificity were evaluated through in vitro experiments. A series of in vivo experiments were then carried out for detecting intraperitoneal tumor xenografts in nude mice by using magnetic resonance (MR) imaging technique. The results revealed that the NaGdF(4)-PEG-mAb probes possessed satisfying tumor-specific targeting ability and strong MR contrast enhancement effects.

    http://http://dx.doi.org/10.1021/nn304837c

  • 6
    Dong C, Zhao H, Yang S, Shi J, Huang J, Cui L, Zhong L, Jin X, Li F, Liu Z, Jia B, Wang F. (99m)Tc-labeled dimeric octreotide peptide: a radiotracer with high tumor uptake for single-photon emission computed tomography imaging of somatostatin receptor subtype 2-positive tumors. Mol Pharm. 2013;10:2925-2933.
  • 7
    Cui L, Liu Z, Jin X, Jia B, Li F, Wang F. Evaluation of 188Re-MAG2-RGD-bombesin for potential prostate cancer therapy. Nucl Med Biol. 2013;40:182-189.

    Abstract

    Glu-RGD-bombesin (RGD-BBN) is a heterodimeric peptide that contains motifs recognizing both integrin α(v)β(3) and gastrin releasing peptide receptor (GRPR). We evaluated here (188)Re (t(1/2)=16.9 h) labeled RGD-BBN as a potential agent for radionuclide therapy of prostate cancer. RGD-BBN was conjugated with S-benzoylmercaptoacetylglycylglycyl (MAG(2)), and then labeled with (99m)Tc or (188)Re, respectively. The dual-receptor binding affinity of MAG(2)-RGD-BBN was investigated by a radioligand competition binding assay. Biodistribution study of (188)Re-MAG(2)-RGD-BBN was carried out in normal BALB/c mice and PC-3 human prostate tumor-bearing nude mice. Gamma imaging studies were performed in PC-3 tumor-bearing nude mice. Biodistribution in normal mice showed that both (99m)Tc and (188)Re-labeled MAG(2)-RGD-BBN possessed high pancreas uptake due to the high GRPR expression of this organ. Gamma imaging with both (99m)Tc and (188)Re-labeled RGD-BBN in PC-3 tumor-bearing nude mice demonstrated high tumor uptake. The PC-3 tumors were clearly visible at 1 postinjection, with high contrast to the contralateral background. The use of chelator MAG(2) enables successful and high-yield (99m)Tc and (188)Re radiolabeling of RGD-BBN with favorable tumor targeting specificity. Further optimization may allow potential clinical application of (188)Re-MAG(2)-RGD-BBN for tumor-targeted radionuclide therapy.

    http://linkinghub.elsevier.com/retrieve/pii/S0969-8051(12)00276-4


  • 8
    Li Y, Liu Z, Dong C, He P, Liu X, Zhu Z, Jia B, Li F, Wang F. Noninvasive detection of human-induced pluripotent stem cell (hiPSC)-derived teratoma with an integrin-targeting agent (99m)Tc-3PRGD2. Mol Imaging Biol. 2013;15:58-67.

    Abstract

    PURPOSE:

    Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have gained increasing interest for tissue regeneration and transplantation therapies. However, teratoma formation after iPSC transplantation is one of the most serious drawbacks that may limit their further clinical application. We investigated here whether human iPSC-derived teratomas could be detected by an integrin-targeting agent (99m)Tc-PEG(4)-E[PEG(4)-c(RGDfK)](2) ((99m)Tc-3PRGD2).

    METHODS:

    Human-induced pluripotent stem cells (hiPSCs) were generated and characterized. In vitro integrin α(v)β(3) expression levels of hiPSC- and hiPSC-derived teratoma cells were determined by flow cytometry. (99m)Tc-3PRGD2 was prepared, and planar gamma imaging and biodistribution studies were carried out in teratoma-bearing severe combined immunodeficient (SCID) mice. Positron emission tomography (PET) imaging of teratomas with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was also performed for comparison. Integrin α(v)β(3) expression in teratoma tissues was determined by immunofluorescence staining.

    RESULTS:

    (99m)Tc-3PRGD2 showed high (2.82 ± 0.21 and 2.69 ± 0.73%ID/g at 0.5 and 1 h pi, respectively) and specific (teratoma uptake decreased from 2.69 ± 0.73 to 0.53 ± 0.26%ID/g after blocking with cold 3PRGD2) uptake in teratoma tissues, and planar gamma imaging demonstrated the feasibility of noninvasively detecting the teratoma formation with (99m)Tc-3PRGD2. (18)F-FDG showed low teratoma uptake and thus failed to detect the teratomas. Ex vivo immunofluorescence staining validated the integrin α(v)β(3) expression in the vasculature during teratoma formation.

    CONCLUSION:

    Gamma imaging with (99m)Tc-3PRGD2 is a promising approach for the noninvasive monitoring of tumorigenicity after hiPSCs transplantation.

    http://dx.doi.org/10.1007/s11307-012-0571-1

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