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      1. Author :
        Templeton, Zachary S.; Bachmann, Michael H.; Alluri, Rajiv V.; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2015
      5. Publication :
        JoVE (Journal of Visualized Experiments)
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        97
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Medicine; Metastatic niche; bone microenvironment; breast cancer metastasis; human bone; osteotropism; <em>ex vivo</em> model; explant culture system; bioluminescence imaging; IVIS; IVIS BLI
      12. Abstract :
        Bone is the most common site of breast cancer metastasis. Although it is widely accepted that the microenvironment influences cancer cell behavior, little is known about breast cancer cell properties and behaviors within the native microenvironment of human bone tissue.We have developed approaches to track, quantify and modulate human breast cancer cells within the microenvironment of cultured human bone tissue fragments isolated from discarded femoral heads following total hip replacement surgeries. Using breast cancer cells engineered for luciferase and enhanced green fluorescent protein (EGFP) expression, we are able to reproducibly quantitate migration and proliferation patterns using bioluminescence imaging (BLI), track cell interactions within the bone fragments using fluorescence microscopy, and evaluate breast cells after colonization with flow cytometry. The key advantages of this model include: 1) a native, architecturally intact tissue microenvironment that includes relevant human cell types, and 2) direct access to the microenvironment, which facilitates rapid quantitative and qualitative monitoring and perturbation of breast and bone cell properties, behaviors and interactions. A primary limitation, at present, is the finite viability of the tissue fragments, which confines the window of study to short-term culture. Applications of the model system include studying the basic biology of breast cancer and other bone-seeking malignancies within the metastatic niche, and developing therapeutic strategies to effectively target breast cancer cells in bone tissues.
      13. URL :
        http://www.jove.com/video/52656
      14. Call Number :
        PKI @ user @ 9332
      15. Serial :
        20350
      1. Author :
        Danino, T.; Prindle, A.; Hasty, J.; Bhatia, S.
      2. Title :
        Measuring growth and gene expression dynamics of tumor-targeted s. Typhimurium bacteria
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        J Vis Exp
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        77
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        The goal of these experiments is to generate quantitative time-course data on the growth and gene expression dynamics of attenuated S. typhimurium bacterial colonies growing inside tumors. We generated model xenograft tumors in mice by subcutaneous injection of a human ovarian cancer cell line, OVCAR-8 (NCI DCTD Tumor Repository, Frederick, MD). We transformed attenuated strains of S. typhimurium bacteria (ELH430:SL1344 phoPQ- (1)) with a constitutively expressed luciferase (luxCDABE) plasmid for visualization(2). These strains specifically colonize tumors while remaining essentially non-virulent to the mouse(1). Once measurable tumors were established, bacteria were injected intravenously via the tail vein with varying dosage. Tumor-localized, bacterial gene expression was monitored in real time over the course of 60 hours using an in vivo imaging system (IVIS). At each time point, tumors were excised, homogenized, and plated to quantitate bacterial colonies for correlation with gene expression data. Together, this data yields a quantitative measure of the in vivo growth and gene expression dynamics of bacteria growing inside tumors.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 5136
      15. Serial :
        14793
      1. Author :
        Abdelwahab, M. G.; Sankar, T.; Preul, M. C.; Scheck, A. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Vis Exp
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        GL261-luc2, IVIS, Glioma, Biolumninescence imaging
      12. Abstract :
        The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The cell line was originally induced by intracranial injection of 3-methyl-cholantrene into a C57BL/6 syngeneic mouse strain (1); therefore, immunologically competent C57BL/6 mice can be used. While we use GL261, the following protocol can be used for the implantation and monitoring of any intracranial mouse tumor model. GL261 cells were engineered to stably express firefly luciferase (GL261-luc). We also created the brighter GL261-luc2 cell line by stable transfection of the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used to eliminate the light attenuation caused by black skin and fur. With the use of albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging system is possible from the day of implantation (Caliper Life Sciences, Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo behavior as the parental GL261 cells. Some of the shared histological features present in human GBMs and this mouse model include: tumor necrosis, pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation (1). Prior to implantation animals were anesthetized by an intraperitoneal injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05 mg/kg), placed in a stereotactic apparatus and an incision was made with a scalpel over the cranial midline. A burrhole was made 0.1mm posterior to the bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of 3mm and withdrawn 0.4mm to a depth of 2.6mm. Two mul of GL261-luc or GL261-luc2 cells (10(7) cells/ml) were infused over the course of 3 minutes. The burrhole was closed with bonewax and the incision was sutured. Following stereotactic implantation the bioluminescent cells are detectable from the day of implantation and the tumor can be analyzed using the 3D image reconstruction feature of the IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150mug luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified using mean tumor bioluminescence over time. Tumor-bearing mice were observed daily to assess morbidity and were euthanized when one or more of the following symptoms are present: lethargy, failure to ambulate, hunched posture, failure to groom, anorexia resulting in >10% loss of weight. Tumors were evident in all of the animals on necropsy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22158303
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10486
      1. Author :
        Ren, Y.; Wang, Y.; Liu, H.; Yan, H.; Chen, J.; Hou, M.; Li, W.; Fan, Y.; Zhou, Q.
      2. Title :
        [Influence of MSA on cell growth and spontaneousn metastasis of L9981-Luc lung cancer transplanted model in nude mice by bioluminescence imaging]
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Zhongguo Fei Ai Za Zhi
      6. Products :
      7. Volume :
        16
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        BACKGROUND AND OBJECTIVE: Methylseleninic acid (MSA) is an artificially developed selenium compound. It has been proven that MSA could inhibit growth and metastasis on many tumor cells. This study investigated whether MSA has an impact on the growth and metastasis of L9981-Luc lung cancer transplanted model in nude mice or not. METHODS: A transplantated tumor model was established in nude mice. Fifteen nude mice were randomly divided into three groups: the control group treated with normal saline (0.2 mL/d), the MSA group treated with MSA solution (0.2 mL), and the cisplatin (DDP) group injected intraperitoneally with DDP (4 mg/kg/w). Inhibition of MSA on tumor growth and tumor metastasis was observed using the IVIS Imaging System 200 Series. RESULTS: A significant difference was obserced in the primary tumor bioluminescence among the three groups (P=0.002) on 21 days post-inoculation. Primary tumor bioluminescence in the DDP group (P=0.001) and in the MSA group (P=0.031) was significantly lower than that in the control group (P=0.001). No significant difference in the metastasis bioluminescence of the thoracic area was indicated among the three groups (P>0.05). CONCLUSIONS: MSA can inhibit the growth of planted tumor of transgenic lung cancer cell lines L9981-Luc in nude mice. MSA may also suppress the distant metastasis of the transplanted tumor of transgenic lung cancer cell lines L9981-Luc in nude mice.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 5143
      15. Serial :
        14776
      1. Author :
        Martins-Marques, Tania; Pinho, Maria Joao; Zuzarte, Monica; Oliveira, Carla; Pereira, Paulo; Sluijter, Joost P. G.; Gomes, Celia; Girao, Henrique
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Extracellular Vesicles
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS BLI in vivo
      12. Abstract :
        Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045474/
      14. Call Number :
        PKI @ user @ 12566
      15. Serial :
        19672
      1. Author :
        Konkalmatt, P. R.; Deng, D.; Thomas, S.; Wu, M. T.; Logsdon, C. D.; French, B. A.; Kelly, K. A.
      2. Title :
        Plectin-1 Targeted AAV Vector for the Molecular Imaging of Pancreatic Cancer
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Front Oncol
      6. Products :
      7. Volume :
        3
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Pancreatic ductal adenocarcinoma (PDAC) is highly malignant disease that is the fourth leading cause of cancer-related death in the US. Gene therapy using AAV vectors to selectively deliver genes to PDAC cells is an attractive treatment option for pancreatic cancer. However, most AAV serotypes display a broad spectrum of tissue tropism and none of the existing serotypes specifically target PDAC cells. This study tests the hypothesis that AAV2 can be genetically re-engineered to specifically target PDAC cells by modifying the capsid surface to display a peptide that has previously been shown to bind plectin-1. Toward this end, a Plectin-1 Targeting Peptide (PTP) was inserted into the loop IV region of the AAV2 capsid, and the resulting capsid (AAV-PTP) was used in a series of in vitro and in vivo experiments. In vitro, AAV-PTP was found to target all five human PDAC cell lines tested (PANC-1, MIA PaCa-2, HPAC, MPanc-96, and BxPC-3) preferentially over two non-neoplastic human pancreatic cell lines (human pancreatic ductal epithelial and human pancreatic stellate cells). In vivo, mice bearing subcutaneous tumor xenografts were generated using the PANC-1 cell line. Once tumors reached a size of approximately 1-2 mm in diameter, the mice were injected intravenously with luciferase reporter vectors packaged in the either AAV-PTP or wild type AAV2 capsids. Luciferase expression was then monitored by bioluminescence imaging on days 3, 7, and 14 after vector injection. The results indicate that the AAV-PTP capsid displays a 37-fold preference for PANC-1 tumor xenographs over liver and other tissues; whereas the wild type AAV2 capsid displays a complementary preference for liver over tumors and other tissues. Together, these results establish proof-of-principle for the ability of PTP-modified AAV capsids to selectively target gene delivery to PDAC cells in vivo, which opens promising new avenues for the early detection, diagnosis, and treatment of pancreatic cancer.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 4201
      15. Serial :
        15007
      1. Author :
        Cernak, I.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Front Neurol
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, RediJect Inflammation Probe, chemiluminescence, XenoLight
      12. Abstract :
        Due to complex injurious environment where multiple blast effects interact with the body parallel, blast-induced neurotrauma is a unique clinical entity induced by systemic, local, and cerebral responses. Activation of autonomous nervous system; sudden pressure increase in vital organs such as lungs and liver; and activation of neuroendocrine-immune system are among the most important mechanisms that contribute significantly to molecular changes and cascading injury mechanisms in the brain. It has been hypothesized that vagally mediated cerebral effects play a vital role in the early response to blast: this assumption has been supported by experiments where bilateral vagotomy mitigated bradycardia, hypotension, and apnea, and also prevented excessive metabolic alterations in the brain of animals exposed to blast. Clinical experience suggests specific blast-body-nervous system interactions such as (1) direct interaction with the head either through direct passage of the blast wave through the skull or by causing acceleration and/or rotation of the head; and (2) via hydraulic interaction, when the blast overpressure compresses the abdomen and chest, and transfers its kinetic energy to the body's fluid phase, initiating oscillating waves that traverse the body and reach the brain. Accumulating evidence suggests that inflammation plays important role in the pathogenesis of long-term neurological deficits due to blast. These include memory decline, motor function and balance impairments, and behavioral alterations, among others. Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in the brain.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21206523
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10420
      1. Author :
        Burlion, Aude; Brunel, Simon; Petit, Nicolas Y.; Olive, Daniel; Marodon, Gilles
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Frontiers in Immunology
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        graft-vs-host disease; graft vs leukemia effect; antibodies; monoclonal; mice; nsg; icOs; cD278; IVIS; IVIS BLI in vivo
      12. Abstract :
        BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells. METHODS: Here, we assessed whether a monoclonal antibody (mAb) to human ICOS was able to antagonize the costimulatory signal delivered in vivo to human T cells. To test this hypothesis, we used a xenogeneic model of GVHD where human peripheral blood mononuclear cells were adoptively transferred in immunocompromised NOD.SCID.gc-null mice (NSG). RESULTS: In this model, control mice invariably lost weight and died by day 50. In contrast, 65% of the mice receiving a single injection of the anti-hICOS mAb survived beyond 100 days. Moreover, a significant improvement in survival was obtained in a curative xeno-GVHD setting. Mechanistically, administration of the anti-hICOS mAb was associated with a strong reduction in perivascular infiltrates in liver and lungs and reduction in frequencies and numbers of human T cells in the spleen. In addition, the mAb prevented T-cell expansion in the blood during xeno-GVHD. Importantly, GVHD-protected mice retained the ability to control the P815 mastocytoma cell line, mimicking GVL in humans. CONCLUSION: A mAb-targeting human ICOS alleviated GVHD without impairing GVL in a xenograft murine model. Thus, ICOS represents a promising target in the management of BMT, preventing GVHD while preserving GVL.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491549/pdf/fimmu-08-00756.pdf
      14. Call Number :
        PKI @ catherine.lautenschlager @ 14092
      15. Serial :
        14185
      1. Author :
        Noble, Richard A.; Bell, Natalie; Blair, Helen; Sikka, Arti; Thomas, Huw; Phillips, Nicole; Nakjang, Sirintra; Miwa, Satomi; Crossland, Rachel; Rand, Vikki; Televantou, Despina; Long, Anna; Keun, Hector C.; Bacon, Chris M.; Bomken, Simon; Critchlow, Susan E.; Wedge, Stephen R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2017
      5. Publication :
        Haematologica
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS BLI in vivo
      12. Abstract :
        Inhibition of monocarboxylate transporter 1 has been proposed as a therapeutic approach to perturb lactate shuttling in tumor cells that lack monocarboxylate transporter 4. We examined the monocarboxylate transporter 1 inhibitor AZD3965, currently in phase I clinical studies, as a potential therapy for diffuse large B-cell lymphoma and Burkitt lymphoma. Whilst extensive monocarboxylate transporter 1 protein was found in 120 diffuse large B-cell lymphoma and 10 Burkitt lymphoma patient tumors, monocarboxylate transporter 4 protein expression was undetectable in 73% of the diffuse large B-cell lymphoma samples and undetectable or negligible in each Burkitt lymphoma sample. AZD3965 treatment led to a rapid accumulation of intracellular lactate in a panel of lymphoma cell lines with low monocarboxylate transporter 4 protein expression and potently inhibited their proliferation. Metabolic changes induced by AZD3965 in lymphoma cells were consistent with a feedback inhibition on glycolysis. A profound cytostatic response was also observed in vivo: daily oral AZD3965 treatment for 24 days, inhibited CA46 Burkitt lymphoma growth by 99%. Continuous exposure of CA46 cells to AZD3965 for 7 weeks in vitro resulted in a greater dependency upon oxidative phosphorylation. Combining AZD3965 with an inhibitor of mitochondrial Complex I (central to oxidative phosphorylation) induced significant lymphoma cell death in vitro and reduced CA46 disease burden in vivo. These data support clinical examination of AZD3965 in Burkitt lymphoma and diffuse large B-cell lymphoma patients with low tumor monocarboxylate transporter 4 expression and highlight the potential of combination strategies to optimally target the metabolic phenotype of tumors.%U http://www.haematologica.org/content/haematol/early/2017/04/03/haematol.2016.163030.full.pdf
      13. URL :
        http://www.haematologica.org/content/haematol/102/7/1247.full.pdf
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13651
      15. Serial :
        13849
      1. Author :
        López-Iglesias, Ana-Alicia; González-Méndez, Lorena; San-Segundo, Laura; Herrero, Ana B.; Hernández-García, Susana; Martín-Sánchez, Montserrat; Gutiérrez, Norma C.; Paíno, Teresa; Avilés, Pablo; Mateos, María-Victoria; San-Miguel, Jesús F.; Garayoa, Mercedes; Ocio, Enrique M.
      2. Title :
        Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Haematologica
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        multiple myeloma; DNA damage; novel agents; IVIS; IVIS BLI in vivo
      12. Abstract :
        Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests a need for new molecules and combinations that may further inhibit important survival pathways for these tumour cells. In this context, zalypsis is a novel compound derived from marine organisms with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction, and has been already tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with an acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations, not only in vitro, but also ex vivo and especially in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients.%U http://www.haematologica.org/content/haematol/early/2016/08/11/haematol.2016.146076.full.pdf
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 12318
      15. Serial :
        19693