Person: Wang, Ping
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Wang
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Ping
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Wang, Ping
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Publication GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging(American Diabetes Association, 2014) Wang, Ping; Yoo, Byunghee; Yang, Jingsheng; Zhang, Xueli; Ross, Alana; Pantazopoulos, Pamela; Dai, Guangping; Moore, AnnaNoninvasive assessment of pancreatic β-cell mass would tremendously aid in managing type 1 diabetes (T1D). Toward this goal, we synthesized an exendin-4 conjugated magnetic iron oxide–based nanoparticle probe targeting glucagon-like peptide 1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic β-cells. In vitro studies in βTC-6, the β-cell line, showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a significant transverse relaxation time (T2) shortening in the pancreata of mice injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with the nontargeted probe at 7.5 and 24 h after injection. Furthermore, ΔT2 of the pancreata of prediabetic NOD mice was significantly higher than that of diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease of probe accumulation in these animals due to β-cell loss. Of note, ΔT2 of prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We believe our results point to the potential for using this agent for monitoring the disease development and response of T1D to therapy.Publication Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer(Nature Publishing Group, 2017) Yoo, Byunghee; Kavishwar, Amol; Wang, Ping; Ross, Alana; Pantazopoulos, Pamela; Dudley, Michael; Moore, Anna; Medarova, ZdravkaTreatment of stage IV metastatic breast cancer patients is limited to palliative options and represents an unmet clinical need. Here, we demonstrate that pharmacological inhibition of miRNA-10b - a master regulator of metastatic cell viability – leads to elimination of distant metastases in a mouse model of metastatic breast cancer. This was achieved using the miRNA-10b inhibitory nanodrug, MN-anti-miR10b, which consists of magnetic nanoparticles, conjugated to LNA-based miR-10b antagomirs. Intravenous injection of MN-anti-miR10b into mice bearing lung, bone, and brain metastases from breast cancer resulted in selective accumulation of the nanodrug in metastatic tumor cells. Weekly treatments of mice with MN-anti-miR-10b and low-dose doxorubicin resulted in complete regression of pre-existing distant metastases in 65% of the animals and a significant reduction in cancer mortality. These observations were supported by dramatic reduction in proliferation and increase in apoptosis in metastatic sites. On a molecular level, we observed a significant increase in the expression of HOXD10, which is a known target of miRNA-10b. These results represent first steps into the uncharted territory of therapy targeted to the metastatic niche.Publication Molecular Imaging of Stems Cells: In Vivo Tracking and Clinical Translation(Hindawi Publishing Corporation, 2017) Rizzo, Stefania; Petrella, Francesco; Politi, Letterio S.; Wang, PingPublication Characterization of the Praesepe Star Cluster by Photometry and Proper Motions With 2MASS, PPMXL, and Pan-STARRS(IOP Publishing, 2014) Wang, Ping; Chen, Wei; Lin, C. C.; Pandey, A. K.; Huang, C. K.; Panwar, N.; Lee, C. H.; Tsai, M. F.; Tang, C.-H.; Goldman, B.; Burgett, W. S.; Chambers, K. C.; Draper, P. W.; Flewelling, H.; Grav, T.; Heasley, J. N.; Hodapp, K. W.; Huber, M. E.; Jedicke, R.; Kaiser, N.; Kudritzki, R.-P.; Luppino, G. A.; Lupton, R. H.; Magnier, E. A.; Metcalfe, N.; Monet, D. G.; Morgan, J. S.; Onaka, P. M.; Price, P. A.; Stubbs, Christopher; Sweeney, W.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.Membership identification is the first step in determining the properties of a star cluster. Low-mass members in particular could be used to trace the dynamical history, such as mass segregation, stellar evaporation, or tidal stripping, of a star cluster in its Galactic environment. We identified member candidates of the intermediate-age Praesepe cluster (M44) with stellar masses ~0.11-2.4 M ☉, using Panoramic Survey Telescope And Rapid Response System and Two Micron All Sky Survey photometry, and PPMXL proper motions. Within a sky area of 3° radius, 1040 candidates are identified, of which 96 are new inclusions. Using the same set of selection criteria on field stars, an estimated false positive rate of 16% was determined, suggesting that 872 of the candidates are true members. This most complete and reliable membership list allows us to favor the BT-Settl model over other stellar models. The cluster shows a distinct binary track above the main sequence, with a binary frequency of 20%-40%, and a high occurrence rate of similar mass pairs. The mass function is consistent with that of the disk population but shows a deficit of members below 0.3 solar masses. A clear mass segregation is evidenced, with the lowest-mass members in our sample being evaporated from this disintegrating cluster.Publication Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics(Hindawi Publishing Corporation, 2016) Wang, Ping; Petrella, Francesco; Nicosia, Luca; Bellomi, Massimo; Rizzo, StefaniaStem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging.Publication Combined Small Interfering RNA Therapy and In Vivo Magnetic Resonance Imaging in Islet Transplantation(American Diabetes Association, 2011) Wang, Ping; Yigit, Mehmet V; Medarova, Zdravka; Wei, Lingling; Dai, Guangping; Schuetz, Christian; Moore, AnnaOBJECTIVE Recent advances in human islet transplantation are hampered by significant graft loss shortly after transplantation and inability to follow islet fate directly. Both issues were addressed by utilizing a dual-purpose therapy/imaging small interfering RNA (siRNA)-nanoparticle probe targeting apoptotic-related gene caspase-3. We expect that treatment with the probe would result in significantly better survival of transplanted islets, which could be monitored by in vivo magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS We synthesized a probe consisting of therapeutic (siRNA to human caspase-3) and imaging (magnetic iron oxide nanoparticles, MN) moieties. In vitro testing of the probe included serum starvation of the islets followed by treatment with the probe. Caspase-3 gene silencing and protein expression were determined by RT-PCR and Western blot, respectively. In vivo studies included serial MRI of NOD-SCID mice transplanted with MN-small interfering (si)Caspase-3–labeled human islets under the left kidney capsule and MN-treated islets under the right kidney capsule. RESULTS Treatment with MN-siCaspase-3 probe resulted in decrease of mRNA and protein expression in serum-starved islets compared with controls. In vivo MRI showed that there were significant differences in the relative volume change between MN-siCaspase-3–treated grafts and MN-labeled grafts. Histology revealed decreased caspase-3 expression and cell apoptosis in MN-siCaspase-3–treated grafts compared with the control side. CONCLUSIONS Our data show the feasibility of combining siRNA therapy and in vivo monitoring of transplanted islets in mice. We observed a protective effect of MN-siCaspase-3 in treated islets both in vitro and in vivo. This study could potentially aid in increasing the success of clinical islet transplantation.