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- 저자 : Martin G. Pomper (검색결과 4 건)
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변영주,Mrudula Pullambhatla,Haofan Wang,Ronnie C. Mease,Martin G. Pomper 한국고분자학회 2013 Macromolecular Research Vol.21 No.5
Prostate-specific membrane antigen (PSMA) is an attractive target for the imaging of prostate cancer (PCa) due to the elevated expression on the surface of prostate tumor cells. Most PSMA-targeted low molecular weight imaging agents are inhibitors of PSMA. We have synthesized a series of substrate-based PSMA-targeted imaging agents by mimicking poly-γ-glutamyl folic acid, an endogenous substrate of PSMA. In vitro the γ-linked polyglutamate conjugates proved to be better substrates than the corresponding α-linked glutamates. However, in vivo imaging studies of γ-ray-emitting and γ-linked glutamates did not demonstrate selective uptake in PSMA-positive over PSMA-negative tumors. Subsequent chromatographic studies and in silico molecular dynamics simulations indicated that hydrolysis of the substrates is slow and access to the enzymatic active site is limited. These results inform the design of future substrate-based imaging agents for PSMA.
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Park, Jong-Sung,Oh, Yumin,Park, Ogyi,Foss, Catherine A.,Lim, Sung Mook,Jo, Dong-Gyu,Na, Dong Hee,Pomper, Martin G.,Lee, Kang Choon,Lee, Seulki Elsevier 2017 Journal of controlled release Vol.267 No.-
<P><B>Abstract</B></P> <P>TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand that can induce apoptosis in cells expressing its cognate death receptors (DRs). Previously, we demonstrated the therapeutic potential of recombinant human TRAIL in experimental rheumatoid arthritis (RA) models. However, the mechanisms of how DR-mediated apoptosis elicits these actions is not known. Here, we show that systemically administering a potent, long-acting PEGylated TRAIL (TRAIL<SUB>PEG</SUB>) is profoundly anti-rheumatic against two complementary experimental RA mouse models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA), <I>via</I> targeting IL-17 secreting Th17 cells and regulatory T cells (Treg). Systemic administration of TRAIL<SUB>PEG</SUB> after disease onset ameliorated the severity of inflammatory arthritis including arthritis indices, paw thickness, cartilage damage and neutrophil infiltration in both CIA and CAIA models. Additionally, the levels of inflammatory molecules (p-p65, ICAM-1, Cox-2, MMP3, and iNOS), pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-6, IL-17) and accumulation of activated macrophages were significantly reduced after the TRAIL<SUB>PEG</SUB> treatment. Importantly, TRAIL<SUB>PEG</SUB> decreased the number of pro-inflammatory Th17 cells in inflamed arthritic joints through TRAIL-induced apoptosis while increasing anti-inflammatory Treg population <I>in vivo</I>. These results suggest that TRAIL<SUB>PEG</SUB> ameliorates autoimmunity by targeting the Th 17-Tregs axis, making it a promising candidate drug for the treatment of RA.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Molecular Imaging of CXCL12 Promoter-driven HSV1-TK Reporter Gene Expression
Lina Alon,Dara L. Kraitchman,Michael Schär,Angel Cortez,Nirbhay N. Yadav,Rebecca Krimins,Peter V. Johnston,Michael T. McMahon,Peter C. M. van Zijl,Sridhar Nimmagadda,Martin G. Pomper,Jeff W. M. Bulte 한국생물공학회 2018 Biotechnology and Bioprocess Engineering Vol.23 No.2
The C-X-C motif chemokine 12 (CXCL12, SDF1a) and its receptor, CXCR4, play a fundamental role in several biological processes, including hematopoiesis, cardiogenesis, cancer progression, and stem cell migration. Noninvasive monitoring of CXCL12 is highly desirable for optimizing strategies that combine mobilization of therapeutic cells to combat cancer or to assist in cardiac tissue repair after myocardial infarction. Here, we report on an MRI reporter gene system for directly monitoring CXCL12 expression in vivo. Glioma cells and human adipose-derived stem cells (hADSC) were transduced with the herpes simplex virus type-1-thymidine kinase (HSV1- tk) reporter gene expressed under the CXCL12 promoter. HSV1-tk expression resulted in accumulation of the PET tracer [125I]FIAU in vitro and in vivo and induced cell death after ganciclovir treatment. Furthermore, the results show that conditional expression of the reporter gene can be induced by hypoxia in transduced cells. Transduced hADSC were incubated with the CEST MRI probe 5-methyl-5, 6- dihydrothymidine (5-MDHT) and transplanted into swine heart. Transplanted cells were clearly visible on Chemical Exchange Saturation Transfer (CEST) MRI using a 3T clinical scanner. Therefore, we conclude that it is possible to image CXCL12 expression with MRI in a large animal model, opening up a possible route to clinical translation.
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Lee, Sangmin,Jung, Seulhee,Koo, Heebeom,Na, Jin Hee,Yoon, Hong Yeol,Shim, Man Kyu,Park, Jooho,Kim, Jong-Ho,Lee, Seulki,Pomper, Martin G.,Kwon, Ick Chan,Ahn, Cheol-Hee,Kim, Kwangmeyung IPC Science and Technology Press 2017 Biomaterials Vol.148 No.-
<P><B>Abstract</B></P> <P>Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated <I>N</I>-azidoacetyl-<SMALL> <I>D</I> </SMALL>-mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated ‘artificial chemical receptors’ containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells <I>in vivo</I> after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as ‘artificial chemical receptors’ that were conjugated to bioorthogonal chemical group-containing liposomes via <I>in vivo</I> click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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