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      1. Author :
        Baddour, Ralph E; Dadani, Farhan N; Kolios, Michael C; Bisland, Stuart K
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Journal of biological physics
      6. Products :
      7. Volume :
        33
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Xen29
      12. Abstract :
        Ultrasound imaging is proving to be an important tool for medical diagnosis of dermatological disease. Backscatter spectral profiles using high-frequency ultrasound (HFUS, 10-100 MHz) are sensitive to subtle changes in eukaryotic cellular morphology and mechanical properties that are indicative of early apoptosis, the main type of cell death induced following photodynamic therapy (PDT). We performed experiments to study whether HFUS could also be used to discern changes in bacteria following PDT treatment. Pellets of planktonic Staphylococcus aureus were treated with different PDT protocols and subsequently interrogated with HFUS. Changes in ultrasound backscatter response were found to correlate with antimicrobial effect. Despite their small size, distinct changes in bacterial morphology that are indicative of cell damage or death are detectable by altered backscatter spectra from bacterial ensembles using HFUS. This highlights the potential for HFUS in rapidly and non-invasively assessing the structural changes related to antimicrobial response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19669553
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9052
      1. Author :
        Xiao, Kai; Luo, Juntao; Fowler, Wiley L; Li, Yuanpei; Lee, Joyce S; Xing, Li; Cheng, R Holland; Wang, Li; Lam, Kit S
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        30
      8. Issue :
        30
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Albumins; Animals; Antineoplastic Agents; Biocompatible Materials; Bioware; Cell Line, Tumor; Drug Delivery Systems; Emulsifying Agents; Female; Humans; Male; Maximum Tolerated Dose; Mice; Mice, Nude; Nanoparticles; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; SKOV3-luc-D3 cells; Spectroscopy, Near-Infrared
      12. Abstract :
        Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs for the treatment of a variety of cancers. However, it is associated with serious side effects caused by PTX itself and the Cremophor EL emulsifier. In the present study, we report the development of a well-defined amphiphilic linear-dendritic copolymer (named as telodendrimer) composed of polyethylene glycol (PEG), cholic acid (CA, a facial amphiphilic molecule) and lysine, which can form drug-loaded core/shell micelles when mixed with hydrophobic drug, such as PTX, under aqueous condition. We have used PEG(5k)-CA(8), a representive telodendrimer, to prepare paclitaxel-loaded nanoparticles (PTX-PEG(5k)-CA(8) NPs) with high loading capacity (7.3 mg PTX/mL) and a size of 20-60 nm. This novel nanoformulation of PTX was found to exhibit similar in vitro cytotoxic activity against ovarian cancer cells as the free drug (Taxol) or paclitaxel/human serum albumin nanoaggregate (Abraxane). The maximum tolerated doses (MTDs) of PTX-PEG(5k)-CA(8) NPs after single dose and five consecutive daily doses in mice were approximately 75 and 45 mg PTX/kg, respectively, which were 2.5-fold higher than those of Taxol. In both subcutaneous and orthotopic intraperitoneal murine models of ovarian cancer, PTX-PEG(5k)-CA(8) NPs achieved superior toxicity profiles and anti-tumor effects compared to Taxol and Abraxane at equivalent PTX doses, which were attributed to their preferential tumor accumulation, and deep penetration into tumor tissue, as confirmed by near infrared fluorescence (NIRF) imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19660809
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9013
      1. Author :
        Kirby, A. C.; Beattie, L.; Maroof, A.; Rooijen, N. van; Kaye, P. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        American Journal of Pathology
      6. Products :
      7. Volume :
        175
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen10
      12. Abstract :
        Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L. donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1? red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1+ marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19644016
      14. Call Number :
        139699
      15. Serial :
        7610
      1. Author :
        Ignat M, Aprahamian M, Lindner V, Altmeyer A, Perretta S, Dallemagne B, Mutter D and Marescaux J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Gastroenterology
      6. Products :
      7. Volume :
        137
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense; AngioSense; AngioSpark; in vivo imaging; pancreatic cancer
      12. Abstract :
        BACKGROUND & AIMS: Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats.

        METHODS: FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.8-microm resolution) in a rat model of pancreatic ductal adenocarcinoma. A preliminary study described the FCFM rendering of normal and pathologic tissues. Subsequently, 2 double-blind studies compared FCFM to standard histology in (1) detection of tumors in rat models of cancer and controls and (2) detection of nodal involvement (splenic, celiac, mesenteric, and colic) 4, 5, and 6 weeks after tumor induction vs controls.

        RESULTS: Tumor cells displayed a fluorescent ductal pattern compared with non-fluorescent normal pancreas or normal follicular pattern of lymph nodes (LNs). FCFM detected all the pancreatic tumors (1.7-mm mean diameter) and identified 23 LNs that contained metastases of 99 LNs examined. Standard histologic analyses resulted in 1 false-negative result in tumor detection and 2 false negatives in LN detection, whereas FCFM produced no false-negative results. Additional serial sectioning confirmed all tumors and 16 metastatic LNs; FCFM had a negative predictive value of 100% and a positive predictive value of 69.6%.

        CONCLUSIONS: Real-time “virtual biopsy” using FCFM detects tumors and LN metastases with 100% sensitivity and 92.2% specificity in rats, making it a reliable technique for detection and staging of pancreatic cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19632230
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4540
      1. Author :
        Li, Min; Rigby, Kevin; Lai, Yuping; Nair, Vinod; Peschel, Andreas; Schittek, Birgit; Otto, Michael
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        53
      8. Issue :
        10
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Anti-Bacterial Agents; Bioware; Blotting, Southern; Chromatography, Thin Layer; Computational Biology; Cytochromes c; Genetic Complementation Test; Humans; Microscopy, Electron, Scanning; Microscopy, Immunoelectron; Mutagenesis; Peptides; Phospholipids; Polymerase Chain Reaction; Staphylococcus aureus; Xen36
      12. Abstract :
        Antimicrobial peptides (AMPs) form an important part of the innate host defense. In contrast to most AMPs, human dermcidin has an anionic net charge. To investigate whether bacteria have developed specific mechanisms of resistance to dermcidin, we screened for mutants of the leading human pathogen, Staphylococcus aureus, with altered resistance to dermcidin. To that end, we constructed a plasmid for use in mariner-based transposon mutagenesis and developed a high-throughput cell viability screening method based on luminescence. In a large screen, we did not find mutants with strongly increased susceptibility to dermcidin, indicating that S. aureus has no specific mechanism of resistance to this AMP. Furthermore, we detected a mutation in a gene of unknown function that resulted in significantly increased resistance to dermcidin. The mutant strain had an altered membrane phospholipid pattern and showed decreased binding of dermcidin to the bacterial surface, indicating that dermcidin interacts with membrane phospholipids. The mode of this interaction was direct, as shown by assays of dermcidin binding to phospholipid preparations, and specific, as the resistance to other AMPs was not affected. Our findings indicate that dermcidin has an exceptional value for the human innate host defense and lend support to the idea that it evolved to evade bacterial resistance mechanisms targeted at the cationic character of most AMPs. Moreover, they suggest that the antimicrobial activity of dermcidin is dependent on the interaction with the bacterial membrane and might thus assist with the determination of the yet unknown mode of action of this important human AMP.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19596877
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9983
      1. Author :
        Priddle, Helen; Grabowska, Anna; Morris, Teresa; Clarke, Philip A; McKenzie, Andrew J; Sottile, Virginie; Denning, Chris; Young, Lorraine; Watson, Sue
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Cloning and stem cells
      6. Products :
      7. Volume :
        11
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Cell Differentiation; Chick Embryo; Embryonic Stem Cells; Fluorescent Dyes; Humans; Luciferases; Luminescent Measurements; Mice; Mice, SCID; PC-3M-luc; Software; Stem Cell Transplantation; Teratoma
      12. Abstract :
        Research into the behavior, efficacy, and biosafety of stem cells with a view to clinical transplantation requires the development of noninvasive methods for in vivo imaging of cells transplanted into animal models. This is particularly relevant for human embryonic stem cells (hESCs), because transplantation of undifferentiated hESCs leads to tumor formation. The present study aimed to monitor hESCs in real time when injected in vivo. hESCs were stably transfected to express luciferase, and luciferase expression was clearly detected in the undifferentiated and differentiated state. When transfected hESCs were injected into chick embryos, bioluminescence could be detected both ex and in ovo. In the SCID mouse model, undifferentiated hESCs were detectable after injection either into the muscle layer of the peritoneum or the kidney capsule. Tumors became detectable between days 10-30, with approximately a 3 log increase in the luminescence signal by day 75. The growth phase occurred earlier in the kidney capsule and then reached a plateau, whilst tumors in the peritoneal wall grew steadily throughout the period analysed. These results show the widespread utility of bioluminescent for in vivo imaging of hESCs in a variety of model systems for preclinical research into regenerative medicine and cancer biology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19522673
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8961
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        26
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bioware; Cell Line, Tumor; Disease Models, Animal; DNA-Binding Proteins; Female; Flow Cytometry; Killer Cells, Natural; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID; Neoplasm Metastasis; Rats
      12. Abstract :
        The occurrence of metastases is a critical determinant of the prognosis for breast cancer patients. Effective treatment of breast cancer metastases is hampered by a poor understanding of the mechanisms involved in the formation of these secondary tumor deposits. To study the processes of metastasis, valid in vivo tumor metastasis models are required. Here, we show that increased expression of the EGF receptor in the MTLn3 rat mammary tumor cell-line is essential for efficient lung metastasis formation in the Rag mouse model. EGFR expression resulted in delayed orthotopic tumor growth but at the same time strongly enhanced intravasation and lung metastasis. Previously, we demonstrated the critical role of NK cells in a lung metastasis model using MTLn3 cells in syngenic F344 rats. However, this model is incompatible with human EGFR. Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2(-/-)gammac(-/-) mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland. In contrast, in nude and SCID mice, the remaining innate immune cells reduce MTLn3 lung metastasis formation. Furthermore, we confirm this finding with the orthotopic transplantation of the 4T1 mouse mammary tumor cell-line. Thus, we have established an improved in vivo model using a Rag2(-/-) gammac(-/-) mouse strain together with MTLn3 cells that have increased levels of the EGF receptor, which enables us to study EGFR-dependent tumor cell autonomous mechanisms underlying lung metastasis formation. This improved model can be used for drug target validation and development of new therapeutic strategies against breast cancer metastasis formation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19466569
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8940
      1. Author :
        Jason R. McCarthy, Purvish Patel, Ion Botnaru, Pouneh Haghayeghi, Ralph Weissleder and Farouc A. Jaffer
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      7. Volume :
        20
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; thrombi; VivoTag
      12. Abstract :
        Thrombosis underlies numerous life-threatening cardiovascular syndromes. Development of thrombosis-specific molecular imaging agents to detect and monitor thrombogenesis and fibrinolysis in vivo could improve the diagnosis, risk stratification, and treatment of thrombosis syndromes. To this end, we have synthesized efficient multimodal nanoagents targeted to two different constituents of thrombi, namely, fibrin and activated factor XIII. These agents are targeted via the conjugation of peptide-targeting ligands to the surface of fluorescently labeled magnetic nanoparticles. As demonstrated by in vitro and in vivo studies, both nanoagents possess high affinities for thrombi, and enable mutimodal fluorescence and magnetic resonance imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19456115
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4647
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