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      1. Author :
        He, T.; Xue, Z.; Lu, K.; Valdivia y Alvarado, M.; Wong, K. K.; Xie, W.; Wong, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Comput Med Imaging Graph
      6. Products :
      7. Volume :
        36
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States, with more than half of the cancers are located peripherally. Computed tomography (CT) has been utilized in the last decade to detect early peripheral lung cancer. However, due to the high false diagnosis rate of CT, further biopsy is often necessary to confirm cancerous cases. This renders intervention for peripheral lung nodules (especially for small peripheral lung cancer) difficult and time-consuming, and it is highly desirable to develop new, on-the-spot earlier lung cancer diagnosis and treatment strategies. PURPOSE: The objective of this study is to develop a minimally invasive multimodality image-guided (MIMIG) intervention system to detect lesions, confirm small peripheral lung cancer, and potentially guide on-the-spot treatment at an early stage. Accurate image guidance and real-time optical imaging of nodules are thus the key techniques to be explored in this work. METHODS: The MIMIG system uses CT images and electromagnetic (EM) tracking to help interventional radiologists target the lesion efficiently. After targeting the lesion, a fiber-optic probe coupled with optical molecular imaging contrast agents is used to confirm the existence of cancerous tissues on-site at microscopic resolution. Using the software developed, pulmonary vessels, airways, and nodules can be segmented and visualized for surgical planning; the segmented results are then transformed onto the intra-procedural CT for interventional guidance using EM tracking. Endomicroscopy through a fiber-optic probe is then performed to visualize tumor tissues. Experiments using IntegriSense 680 fluorescent contrast agent labeling alphavbeta3 integrin were carried out for rabbit lung cancer models. Confirmed cancers could then be treated on-the-spot using radio-frequency ablation (RFA). RESULTS: The prototype system is evaluated using the rabbit VX2 lung cancer model to evaluate the targeting accuracy, guidance efficiency, and performance of molecular imaging. Using this system, we achieved an average targeting accuracy of 3.04 mm, and the IntegriSense signals within the VX2 tumors were found to be at least two-fold higher than those of normal tissues. The results demonstrate great potential for applying the system in human trials in the future if an optical molecular imaging agent is approved by the Food and Drug Administration (FDA). CONCLUSIONS: The MIMIG system was developed for on-the-spot interventional diagnosis of peripheral lung tumors by combining image-guidance and molecular imaging. The system can be potentially applied to human trials on diagnosing and treating earlier stage lung cancer. For current clinical applications, where a biopsy is unavoidable, the MIMIG system without contrast agents could be used for biopsy guidance to improve the accuracy and efficiency.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22483054
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10364
      1. Author :
        Pribaz, J. R.; Bernthal, N. M.; Billi, F.; Cho, J. S.; Ramos, R. I.; Guo, Y.; Cheung, A. L.; Francis, K. P.; Miller, L. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of orthopaedic research : official publication of the Orthopaedic Research Society
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability, and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent Staphylococcus aureus strain (1 x 10(2) -1 x 10(4) colony forming units, CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus strains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40), or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40, and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29, and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo enhanced green fluorescence protein (EGFP)-neutrophil flourescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40, and especially Xen36, which had stable bioluminescent constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions. (c) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21837686
      14. Call Number :
        142237
      15. Serial :
        6983
      1. Author :
        Dernell, William S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        N/A
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        *Breast Cancer; *Chemotherapy; *Genes; *Luciferase; Anatomy and Physiology; Biochemistry; Bioware; Cells(Biology); Diseases; Drugs; Efficacy; Gel Polymers; Gels; Growth(Physiology); Humans; Image Processing; In Vitro Analysis.; In Vivo Analysis; Luciferase Genes; Medicine and Medical Research; Metastasis; Mouse Models; Paclitaxel Sensitivity; Poloxamer Polymers; Polymers; Preclinical Evaluations; surgery; Synergism; Toxicity; Tumor Cell Lines
      12. Abstract :
        This project evaluated paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method was shown to control local tumor disease as well as assist in control of systemic metastasis. We established 5 human breast cancer cell lines within our laboratory. We elected purchase and implement a unique (luciferase) imaging system which allows in vivo imaging of tumor growth and metastasis (and subsequently decrease animal use). Tumor cell lines were transfected with the luciferase gene. In vitro testing of cell lines established paclitaxel sensitivity and showed a synergistic effect of delivering paclitaxel by the poloxamer polymer, especially for the chemotherapy resistant cell line, MCF-7-ADR. We completed the simultaneous evaluation of local and systemic toxicity, local, regional and systemic distribution and local and systemic efficacy of locally delivered paclitaxel chemotherapy following tumor removal using the MCF-7-ADR cell line in nude mice. Intracavitary administration of taxol in poloxamer was well tolerated (locally and systemically) afld resulted in significantly improved control of local tumor regrowth and comparable control of metastasis following marginal tumor removal as compared to intravenous paclitaxel (parent drug) . Sustained drug levels (from polymer delivery) were seen in plasma and liver tissue at 60 days.
      13. URL :
        http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA437225
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8994
      1. Author :
        Welti, J. C.; Powles, T.; Foo, S.; Gourlaouen, M.; Preece, N.; Foster, J.; Frentzas, S.; Bird, D.; Sharpe, K.; van Weverwijk, A.; Robertson, D.; Soffe, J.; Erler, J. T.; Pili, R.; Springer, C. J.; Mather, S. J.; Reynolds, A. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        15
      8. Issue :
        N/A
      9. Page Numbers :
        623-41
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, 4T1, Bioware, IVIS
      12. Abstract :
        Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastases in Balb/c mice, to re-address the effects of sunitinib on the progression of metastatic disease in mice. We show that treatment of mice with sunitinib prior to intravenous injection of tumour cells can promote the seeding and growth of 4T1 lung metastases, but not RENCA lung metastases, showing that this effect is cell line dependent. However, increased metastasis occurred only upon administration of a very high sunitinib dose, but not when lower, clinically relevant doses were used. Mechanistically, high dose sunitinib led to a pericyte depletion effect in the lung vasculature that correlated with increased seeding of metastasis. By administering sunitinib to mice after intravenous injection of tumour cells, we demonstrate that while sunitinib does not inhibit the growth of 4T1 lung tumour nodules, it does block the growth of RENCA lung tumour nodules. This contrasting response was correlated with increased myeloid cell recruitment and persistent vascularisation in 4T1 tumours, whereas RENCA tumours recruited less myeloid cells and were more profoundly devascularised upon sunitinib treatment. Finally, we show that progression of 4T1 tumours in sunitinib treated mice results in increased hypoxia and increased glucose metabolism in these tumours and that this is associated with a poor outcome. Taken together, these data suggest that the effects of sunitinib on tumour progression are dose-dependent and tumour model-dependent. These findings have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22843200
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10504
      1. Author :
        Liao, A. H.; Li, Y. K.; Lee, W. J.; Wu, M. F.; Liu, H. L.; Kuo, M. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Ultrasound Med Biol
      6. Products :
      7. Volume :
        38
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, IVIS, Bioluminescence
      12. Abstract :
        The application of drug-loaded microbubbles (MBs) in combination with ultrasound (US), which results in an increase in capillary permeability at the site of US-sonication-induced MB destruction, may be an efficient method of localized drug delivery. This study investigated the mechanism underlying the US-mediated release of luciferin-loaded MBs through the blood vessels to targeted cells using an in vivo bioluminescence imaging (BLI) system. The luciferin-loaded MBs comprised an albumin shell with a diameter of 1234 +/- 394 nm (mean +/- SD) and contained 2.48 x 10(9) bubbles/mL; within each MB, the concentration of encapsulated luciferin was 1.48 x 10(-)(1)(0) mg/bubble. The loading efficiency of luciferin in MBs was only about 19.8%, while maintaining both the bioluminescence and acoustic properties. In vitro and in vivo BLI experiments were performed to evaluate the US-mediated release of luciferin-loaded MBs. For in vitro results, the increase in light emission of luciferin-loaded albumin-shelled MBs after destruction via US sonication (6.24 +/- 0.72 x 10(7) photons/s) was significantly higher than that in the luciferin-loaded albumin-shelled MBs (3.11 +/- 0.33 x 10(7) photons/s) (p < 0.05). The efficiency of the US-mediated release of luciferin-loaded MBs in 4T1-luc2 tumor-bearing mice was also estimated. The signal intensity of the tumor with US destruction at 3 W/cm(2) for 30 s was significantly higher than without US destruction at 3 (p = 0.025), 5 (p = 0.013), 7 (p = 0.012) and 10 (p = 0.032) min after injecting luciferin-loaded albumin-shelled MBs. The delivery efficiency was, thus, improved with US-mediated release, allowing reduction of the total injection dose of luciferin.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22929655
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10481
      1. Author :
        von Schwarzenberg, K.; Wiedmann, R. M.; Oak, P.; Schulz, S.; Zischka, H.; Wanner, G.; Efferth, T.; Trauner, D.; Vollmar, A. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Biol Chem
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, IVIS, Bioluminescence
      12. Abstract :
        The vacuolar H+-ATPase (V-ATPase), a multisubunit proton pump, has come into focus as an attractive target in cancer invasion. However little is known about the role of V-ATPase in cell death and especially the underlying mechanisms remain mostly unknown. We used the myxobacterial macrolide archazolid B, a potent inhibitor of the V-ATPase, as an experimental drug as well as a chemical tool to decipher V-ATPase related cell death signaling. We found that archazolid induced apoptosis in highly invasive tumor cells at nanomolar concentrations which was executed by the mitochondrial pathway. Prior to apoptosis induction archazolid lead to the activation of a cellular stress response including activation of the hypoxia-inducible factor-1 alpha (HIF1alpha) and autophagy. Autophagy was induced at low concentrations of archazolid that do not alter pH in lysosomes and was shown by degradation of p62 or fusion of autophagosomes with lysosomes. HIF1alpha was induced due to energy stress shown by a decline of the ATP level and followed by a shut down of energy consuming processes. As silencing HIF1alpha increases apoptosis, the cellular stress response was suggested to be a survival mechanism. We conclude that archazolid leads to energy stress which activates adaptive mechanisms like autophagy mediated by HIF1alpha and finally leads to apoptosis. We propose V-ATPase as a promising drugable target in cancer therapy caught up at the interplay of apoptosis, autophagy and cellular/metabolic stress.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23168408
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10480
      1. Author :
        Zhang, Z.; Hu, Z.; Gupta, J.; Krimmel, J. D.; Gerseny, H. M.; Berg, A. F.; Robbins, J. S.; Du, H.; Prabhakar, B.; Seth, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Gene Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, IVIS, Bioluminescence, Adenoviridae/genetics/*metabolism/physiology; Administration, Intravenous; Animals; Bone Neoplasms/secondary/*therapy; Cell Line, Tumor; Female; Humans; Immunocompetence; Luminescent Measurements/methods; Mammary Neoplasms, Experimental/pathology/*therapy; Mice; Mice, Inbred BALB C; Oncolytic Virotherapy/methods; Oncolytic Viruses/genetics/metabolism/physiology; Phosphorylation; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases/genetics/*metabolism; Receptors, Transforming Growth Factor beta/genetics/*metabolism; Signal Transduction; Smad2 Protein/genetics/metabolism; Telomerase/genetics; Transforming Growth Factor beta1/genetics/metabolism; Transplantation, Isogeneic/methods; Tumor Stem Cell Assay/methods; Virus Replication
      12. Abstract :
        We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFbetaRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTbetaRFc, or with two oncolytic adenoviruses, Ad.sTbetaRFc and TAd.sTbetaRFc, expressing sTGFbetaRIIFc (the human TERT promoter drives viral replication in TAd.sTbetaRFc) produced sTGFbetaRIIFc protein. Oncolytic adenoviruses produced viral replication and induced cytotoxicity in 4T1 cells. 4T1 cells were resistant to the cytotoxic effects of TGFbeta-1 (up to 10 ng ml(-1)). However, TGFbeta-1 induced the phosphorylation of SMAD2 and SMAD3, which were inhibited by co-incubation with sTGFbetaRIIFc protein. TGFbeta-1 also induced interleukin-11, a well-known osteolytic factor. Intracardiac injection of 4T1-luc2 cells produced bone metastases by day 4. Intravenous injection of Ad.sTbetaRFc (on days 5 and 7) followed by bioluminescence imaging (BLI) of mice on days 7, 11 and 14 in tumor-bearing mice indicated inhibition of bone metastasis progression (P<0.05). X-ray radiography of mice on day 14 showed a significant reduction of the lesion size by Ad.sTbetaRFc (P<0.01) and TAd.sTbetaRFc (P<0.05). Replication-deficient virus Ad(E1-).sTbetaRFc expressing sTGFbetaRIIFc showed some inhibition of bone metastasis, whereas Ad(E1-).Null was not effective in inhibiting bone metastases. Thus, systemic administration of Ad.sTbetaRFc and TAd.sTbetaRFc can inhibit bone metastasis in the 4T1 mouse mammary tumor model, and can be developed as potential anti-tumor agents for breast cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22744210
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10479
      1. Author :
        Xie, B. W.; Mol, I. M.; Keereweer, S.; van Beek, E. R.; Que, I.; Snoeks, T. J.; Chan, A.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, ProSense, MMPSense, CRi, Maestro, IVIS Animals; Benzenesulfonates/diagnostic use; Diagnostic Imaging/instrumentation/*methods; Disease Models, Animal; Disease Progression; Fluorescent Dyes/*diagnostic use; Indoles/diagnostic use; Luminescent Measurements/instrumentation/*methods; Mammary Neoplasms, Experimental/*diagnosis/pathology; Mice
      12. Abstract :
        Bioluminescence imaging (BLI) has shown its appeal as a sensitive technique for in vivo whole body optical imaging. However, the development of injectable tumor-specific near-infrared fluorescent (NIRF) probes makes fluorescence imaging (FLI) a promising alternative to BLI in situations where BLI cannot be used or is unwanted (e.g., spontaneous transgenic tumor models, or syngeneic mice to study immune effects).In this study, we addressed the questions whether it is possible to detect tumor progression using FLI with appropriate sensitivity and how FLI correlates with BLI measurements. In addition, we explored the possibility to simultaneously detect multiple tumor characteristics by dual-wavelength FLI (~700 and ~800 nm) in combination with spectral unmixing. Using a luciferase-expressing 4T1-luc2 mouse breast cancer model and combinations of activatable and targeting NIRF probes, we showed that the activatable NIRF probes (ProSense680 and MMPSense680) and the targeting NIRF probes (IRDye 800CW 2-DG and IRDye 800CW EGF) were either activated by or bound to 4T1-luc2 cells. In vivo, we implanted 4T1-luc2 cells orthotopically in nude mice and were able to follow tumor progression longitudinally both by BLI and dual-wavelength FLI. We were able to reveal different probe signals within the tumor, which co-localized with immuno-staining. Moreover, we observed a linear correlation between the internal BLI signals and the FLI signals obtained from the NIRF probes. Finally, we could detect pulmonary metastases both by BLI and FLI and confirmed their presence histologically.Taken together, these data suggest that dual-wavelength FLI is a feasible approach to simultaneously detect different features of one tumor and to follow tumor progression with appropriate specificity and sensitivity. This study may open up new perspectives for the detection of tumors and metastases in various experimental models and could also have clinical applications, such as image-guided surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22348134
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10426
      1. Author :
        Beck, Benjamin H; Kim, Hyung-Gyoon; Kim, Hyunki; Samuel, Sharon; Liu, Zhiyong; Shrestha, Robin; Haines, Hilary; Zinn, Kurt; Lopez, Richard D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast cancer research and treatment
      6. Products :
      7. Volume :
        122
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Adenocarcinoma; Animals; Bioware; Breast Neoplasms; Cell Line, Tumor; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Female; Humans; Immunotherapy, Adoptive; Indium Radioisotopes; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Radiopharmaceuticals; Receptors, Antigen, T-Cell, gamma-delta; Spleen; Tissue Distribution; T-Lymphocyte Subsets; Tomography, Emission-Computed, Single-Photon; Transplantation, Heterologous; Transplantation, Isogeneic
      12. Abstract :
        In contrast to antigen-specific alphabeta-T cells (adaptive immune system), gammadelta-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the well-documented capacity of gammadelta-T cells to innately kill a variety of malignant cells, efforts are now actively underway to exploit the antitumor properties of gammadelta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gammadelta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively transferred gammadelta-T cells would be employed therapeutically against breast cancer. Using radioisotope-labeled gammadelta-T cells, we first show that adoptively transferred gammadelta-T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma) of human breast cancer. Moreover, by using an antibody directed against the gammadelta-T cell receptor (TCR), we determined that localization of adoptively transferred gammadelta-T cells to tumor is a TCR-dependant process. Additionally, biodistribution studies revealed that adoptively transferred gammadelta-T cells traffic differently in tumor-bearing mice compared to healthy mice with fewer gammadelta-T cells localizing into the spleens of tumor-bearing mice. Finally, in both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we demonstrate that adoptively transferred gammadelta-T cells are both effective against breast cancer and are otherwise well-tolerated by treated animals. These findings provide a strong preclinical rationale for using ex vivo expanded adoptively transferred gammadelta-T cells as a form of cell-based immunotherapy for the treatment of breast cancer. Additionally, these studies establish that clinically applicable methods for radiolabeling gammadelta-T cells allows for the tracking of adoptively transferred gammadelta-T cells in tumor-bearing hosts.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19763820
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8939
      1. Author :
        Kim, Jae-Beom; Urban, Konnie; Cochran, Edward; Lee, Steve; Ang, Angel; Rice, Bradley; Bata, Adam; Campbell, Kenneth; Coffee, Richard; Gorodinsky, Alex; Lu, Zhan; Zhou, He; Kishimoto, Takashi Kei; Lassota, Peter
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PloS one
      6. Products :
      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bicuculline; Bioware; Cell Line, Tumor; Diagnostic Imaging; Female; Genetic Vectors; Lentivirus; Luciferases; Luminescent Measurements; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20186331
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8938