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      1. Author :
        Lu, Ko-Hsiu; Chen, Pei-Ni; Hsieh, Yi-Hsien; Lin, Chin-Yin; Cheng, Fu-Yuan; Chiu, Peng-Chou; Chu, Shu-Chen; Hsieh, Yih-Shou
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Food and Chemical Toxicology
      6. Products :
      7. Volume :
        97
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        FAK-Src; MEK/ERK; Metastasis; Osteosarcoma; RhoA/MLC2; 3-Hydroxyflavone; IVIS; IVIS BLI in vivo
      12. Abstract :
        Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 μM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin. 3-hydroxyflavone significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-steroid receptor coactivator (Src), p-mitogen/extracellular signal-regulated kinase (MEK)1/2, p-myosin light chain (MLC)2 Ser19, epithelial cell adhesion molecule, Ras homolog gene family (Rho)A and fibronectin expressions. 3-hydroxyflavone also affected the epithelial-mesenchymal transition (EMT) by down-regulating expressions of Vimentin and α-catenin with activation of the transcription factor Slug. In nude mice xenograft model and tail vein injection model showed that 3-hydroxyflavone reduced 143B tumor growth and lung metastasis. 3-hydroxyflavone possesses the anti-metastatic activity of U2OS and 143B cells by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and suppresses 143B tumor growth in vivo. This may lead to clinical trials of osteosarcoma chemotherapy to confirm the promising result in the future.
      13. URL :
        http://www.sciencedirect.com/science/article/pii/S0278691516303209
      14. Call Number :
        PKI @ user @ 12293
      15. Serial :
        19690
      1. Author :
        McKinley, Eliot T; Smith, R Adam; Zhao, Ping; Fu, Allie; Saleh, Samir A; Uddin, Md Imam; Washington, M Kay; Coffey, Robert J; Manning, H Charles
      2. Title :
        3′-Deoxy-3′-18F-Fluorothymidine PET Predicts Response to V600EBRAF-Targeted Therapy in Preclinical Models of Colorectal Cancer
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Journal of Nuclear Medicine
      6. Products :
      7. Volume :
        54
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Selective inhibition of oncogenic targets and associated signaling pathways forms the basis of personalized cancer medicine. The clinical success of V600EBRAF inhibition in melanoma, coupled with the emergence of acquired resistance, underscores the importance of rigorously validating quantitative biomarkers of treatment response in this and similar settings. Since constitutive activation of BRAF leads to proliferation in tumors, we explored 18F-FLT PET to non-invasively quantify changes in tumor proliferation that are associated with pharmacological inhibition of V600EBRAF downstream effectors and that precede changes in tumor volume. Methods—Human colorectal cancer (CRC) cell lines expressing V600EBRAF were used to explore relationships between up-regulation of p27 and phosphorylation of BRAF downstream effectors upon small molecule V600EBRAF inhibitor exposure. Athymic nude mice bearing V600EBRAF-expressing human CRC cell line xenografts were treated with a small molecule V600EBRAF inhibitor (or vehicle) daily for ten days. Predictive 18F-FLT PET was conducted prior to changes in tumor volume. Correlations were evaluated among PET imaging, inhibition of p-MEK and p-ERK by western blot, tumor proliferation by histology, and small molecule exposure by MALDI imaging mass spectrometry (IMS). Results—Treatment of CRC cell lines with PLX4720 reduced proliferation associated with target inhibition and up regulation of p27. In vivo, PLX4720 treatment reduced 18F-FLT uptake, but not 18F-FDG uptake, in Lim2405 xenografts prior to quantifiable differences in xenograft volume. Reduced 18F-FLT PET reflected a modest, yet significant, reduction of Ki67 immunoreactivity, inhibition of p-MEK and p-ERK, and elevated tumor cell p27 protein levels. Both 18F-FLT PET and 18F-FDG PET accurately reflected a lack response in HT-29 xenografts, which MALDI IMS suggested may have stemmed from limited PLX4720 exposure. Conclusions—We utilized preclinical models of CRC to demonstrate 18F-FLT PET as a sensitive predictor of response to V600EBRAF inhibitors. Since 18F-FLT PET predicted reduced proliferation associated with attenuation of BRAF downstream effectors, yet 18F-FDG PET did not, these data suggest that 18F-FLT PET may represent an alternative to 18F-FDG PET for quantifying clinical responses to BRAF inhibitors.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 4387
      15. Serial :
        14996
      1. Author :
        Roy, D.; Steyer, G. J.; Gargesha, M.; Stone, M. E.; Wilson, D. L.
      2. Title :
        3D cryo-imaging: a very high-resolution view of the whole mouse
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Anat Rec (Hoboken)
      6. Products :
      7. Volume :
        292
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Actins/genetics, Animals, Automation, Diagnostic Imaging, Fluorescence, Green Fluorescent Proteins/genetics/metabolism, Image Processing, Computer-Assisted, Imaging, Three-Dimensional/ methods, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Promoter Regions, Genetic, Whole Body Imaging
      12. Abstract :
        We developed the Case Cryo-imaging system that provides information rich, very high-resolution, color brightfield, and molecular fluorescence images of a whole mouse using a section-and-image block-face imaging technology. The system consists of a mouse-sized, motorized cryo-microtome with special features for imaging, a modified, brightfield/fluorescence microscope, and a robotic xyz imaging system positioner, all of which is fully automated by a control system. Using the robotic system, we acquired microscopic tiled images at a pixel size of 15.6 microm over the block face of a whole mouse sectioned at 40 microm, with a total data volume of 55 GB. Viewing 2D images at multiple resolutions, we identified small structures such as cardiac vessels, muscle layers, villi of the small intestine, the optic nerve, and layers of the eye. Cryo-imaging was also suitable for imaging embryo mutants in 3D. A mouse, in which enhanced green fluorescent protein was expressed under gamma actin promoter in smooth muscle cells, gave clear 3D views of smooth muscle in the urogenital and gastrointestinal tracts. With cryo-imaging, we could obtain 3D vasculature down to 10 microm, over very large regions of mouse brain. Software is fully automated with fully programmable imaging/sectioning protocols, email notifications, and automatic volume visualization. With a unique combination of field-of-view, depth of field, contrast, and resolution, the Case Cryo-imaging system fills the gap between whole animal in vivo imaging and histology.
      13. URL :
        N/A
      14. Call Number :
        142666
      15. Serial :
        8246
      1. Author :
        Zhao, Yue; Zhu, Dianwen; Baikejiang, Reheman; Li, Changqing
      2. Title :
        3D mouse shape reconstruction based on phase-shifting algorithm for fluorescence molecular tomography imaging system
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Applied Optics
      6. Products :
      7. Volume :
        54
      8. Issue :
        32
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        This work introduces a fast, low-cost, robust method based on fringe pattern and phase shifting to obtain three-dimensional (3D) mouse surface geometry for fluorescence molecular tomography (FMT) imaging. We used two pico projector/webcam pairs to project and capture fringe patterns from different views. We first calibrated the pico projectors and the webcams to obtain their system parameters. Each pico projector/webcam pair had its own coordinate system. We used a cylindrical calibration bar to calculate the transformation matrix between these two coordinate systems. After that, the pico projectors projected nine fringe patterns with a phase-shifting step of 2
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 10346
      15. Serial :
        13464
      1. Author :
        Wang, Kui; Kievit, Forrest M.; Florczyk, Stephen J.; Stephen, Zachary R.; Zhang, Miqin
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Biomacromolecules
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Ivis; Ivis Fli
      12. Abstract :
        Cationic nanoparticles (NPs) for targeted gene delivery are conventionally evaluated using 2D in vitro cultures. However, this does not translate well to corresponding in vivo studies because of the marked difference in NP behavior in the presence of the tumor microenvironment. In this study, we investigated whether prostate cancer (PCa) cells cultured in three-dimensional (3D) chitosan-alginate (CA) porous scaffolds could model cationic NP-mediated gene targeted delivery to tumors in vitro. We assessed in vitro tumor cell proliferation, formation of tumor spheroids, and expression of marker genes that promote tumor malignancy in CA scaffolds. The efficacy of NP-targeted gene delivery was evaluated in PCa cells in 2D cultures, PCa tumor spheroids grown in CA scaffolds, and PCa tumors in a mouse TRAMP-C2 flank tumor model. PCa cells cultured in CA scaffolds grew into tumor spheroids and displayed characteristics of higher malignancy as compared to those in 2D cultures. Significantly, targeted gene delivery was only observed in cells cultured in CA scaffolds, whereas cells cultured on 2D plates showed no difference in gene delivery between targeted and nontarget control NPs. In vivo NP evaluation confirmed targeted gene delivery, indicating that only CA scaffolds correctly modeled NP-mediated targeted delivery in vivo. These findings suggest that CA scaffolds serve as a better in vitro platform than 2D cultures for evaluation of NP-mediated targeted gene delivery to PCa.
      13. URL :
        http://dx.doi.org/10.1021/acs.biomac.5b01032
      14. Call Number :
        PKI @ user @ 10091
      15. Serial :
        20305
      1. Author :
        LaCrue, Alexis N; Sáenz, Fabián E; Cross, R Matthew; Udenze, Kenneth O; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S; Manetsch, Roman; Kyle, Dennis E
      2. Title :
        4 (1H)-quinolones with liver stage activity against Plasmodium berghei
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        57
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luccon) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 3990
      15. Serial :
        14278
      1. Author :
        Liu, Xin; He, Xiaowe; Yan, Zhuangzhi; Lu, Hongbing
      2. Title :
        4-D reconstruction of fluorescence molecular tomography using re-assembled measurement data
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        Biomedical Optics Express
      6. Products :
      7. Volume :
        6
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Fmt
      12. Abstract :
        Challenges remain in the reconstruction of dynamic (4-D) fluorescence molecular tomography (FMT). In our previous work, we implemented a fully 4-D FMT reconstruction approach using Karhunen- Loève (KL) transformation. However, in the reconstruction processes, the input data were scan-by-scan fluorescence projections. As a result, the reconstruction interval is limited by the data acquisition time for scanning one circle projections, leading to a long time (typically >1 min). In this paper, we propose a new method to reduce the reconstruction interval of dynamic FMT imaging, which is achieved by re-assembling the acquired fluorescence projection sequence. Further, to eliminate the temporal correlations within measurement data, the re-assembled projection sequence is reconstructed by the KL-based method. The numerical simulation and in vivo experiments are performed to evaluate the performance of the method. The experimental results indicate that after re-assembling measurement data, the reconstruction interval can be greatly reduced (~2.5 sec/frame). In addition, the proposed re-assembling method is helpful for improving reconstruction quality of the KL-based method.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 9546
      15. Serial :
        13482
      1. Author :
        Roberts, Bracken F.; Zheng, Yongsheng; Cleaveleand, Jacob; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Yuan, Yu; Chakrabarti, Debopam
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        International Journal for Parasitology: Drugs and Drug Resistance
      6. Products :
      7. Volume :
        7
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Antimalarials; Antiplasmodials; Natural-product-like compounds; Styrylquinoline; Invasion inhibitor; IVIS; IVIS BLI in vivo
      12. Abstract :
        Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits a cellular action distinct from current antimalarials, acting early on malaria parasite's intraerythrocytic life cycle including merozoite invasion. The compound is a fast-acting parasitocidal agent and also exhibits curative property in the rodent malaria model when administered orally. In this report, we describe the synthesis, preliminary structure-function analysis, and the parasite developmental stage specific action of the SQ scaffold.
      13. URL :
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350499/pdf/main.pdf
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13411
      15. Serial :
        13790
      1. Author :
        Domnanich, Katharina A.; Müller, Cristina; Farkas, Renata; Schmid, Raffaella M.; Ponsard, Bernard; Schibli, Roger; Türler, Andreas; Meulen, Nicholas P. van der
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        EJNMMI Radiopharmacy and Chemistry
      6. Products :
      7. Volume :
        1
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Ct; G8 Pet
      12. Abstract :
        BackgroundRecently, 44Sc (T1/2 = 3.97 h, Eβ+av = 632 keV, I = 94.3 %) has emerged as an attractive radiometal candidate for PET imaging using DOTA-functionalized biomolecules. The aim of this study was to investigate the potential of using NODAGA for the coordination of 44Sc. Two pairs of DOTA/NODAGA-derivatized peptides were investigated in vitro and in vivo and the results obtained with 44Sc compared with its 68Ga-labeled counterparts.DOTA-RGD and NODAGA-RGD, as well as DOTA-NOC and NODAGA-NOC, were labeled with 44Sc and 68Ga, respectively. The radiopeptides were investigated with regard to their stability in buffer solution and under metal challenge conditions using Fe3+ and Cu2+. Time-dependent biodistribution studies and PET/CT imaging were performed in U87MG and AR42J tumor-bearing mice.ResultsBoth RGD- and NOC-based peptides with a DOTA chelator were readily labeled with 44Sc and 68Ga, respectively, and remained stable over at least 4 half-lives of the corresponding radionuclide. In contrast, the labeling of NODAGA-functionalized peptides with 44Sc was more challenging and the resulting radiopeptides were clearly less stable than the DOTA-derivatized matches. 44Sc-NODAGA peptides were clearly more susceptible to metal challenge than 44Sc-DOTA peptides under the same conditions. Instability of 68Ga-labeled peptides was only observed if they were coordinated with a DOTA in the presence of excess Cu2+. Biodistribution data of the 44Sc-labeled peptides were largely comparable with the data obtained with the 68Ga-labeled counterparts. It was only in the liver tissue that the uptake of 68Ga-labeled DOTA compounds was markedly higher than for the 44Sc-labeled version and this was also visible on PET/CT images. The 44Sc-labeled NODAGA-peptides showed a similar tissue distribution to those of the DOTA peptides without any obvious signs of in vivo instability.ConclusionsAlthough DOTA revealed to be the preferred chelator for stable coordination of 44Sc, the data presented in this work indicate the possibility of using NODAGA in combination with 44Sc. In view of a clinical study, thorough investigations will be necessary regarding the labeling conditions and storage solutions in order to guarantee sufficient stability of 44Sc-labeled NODAGA compounds.
      13. URL :
        http://link.springer.com/article/10.1186/s41181-016-0013-5
      14. Call Number :
        PKI @ user @
      15. Serial :
        11787
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