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      1. Author :
        Smith, B. R.; Kempen, P.; Bouley, D.; Xu, A.; Liu, Z.; Melosh, N.; Dai, H.; Sinclair, R.; Gambhir, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nano Lett
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; *Disease Models, Animal; Ear Neoplasms/*blood supply/pathology; Humans; Mice; Microscopy, Fluorescence; Nanoparticles/*chemistry; *Nanotechnology; Nanotubes, Carbon/chemistry; Neoplasms, Experimental/*blood supply/pathology; Particle Size; Quantum Dots; Surface Properties
      12. Abstract :
        Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22650417
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10439
      1. Author :
        Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Oral Dis
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        427-32
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Maestro, Animals; Bone Density Conservation Agents/administration & dosage/*pharmacokinetics; Bone and Bones/*metabolism; Calcium/metabolism; Chelating Agents; Decalcification Technique; Diphosphonates/administration & dosage/*pharmacokinetics; Durapatite/metabolism; Edetic Acid; Female; Femur/metabolism; Fibula/metabolism; Fluorescent Dyes/diagnostic use; Fluorometry; Humerus/metabolism; Injections, Intravenous; Mandible/metabolism; Models, Animal; Radius/metabolism; Rats; Rats, Nude; Spectrophotometry, Atomic; Tibia/metabolism; Tissue Distribution; Ulna/metabolism
      12. Abstract :
        OBJECTIVES: Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. MATERIALS AND METHODS: Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. RESULTS: Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05). CONCLUSIONS: This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21122034
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10467
      1. Author :
        Yamaoka, Ippei; Kikuchi, Takeshi; Endo, Naoyuki; Ebisu, Goro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        BMC gastroenterology
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        BALB/c CrSlc mice; enteral nutrition; Ex vivo; Gastrosense 750; Hine® E-gel; in vivo; IVIS® Spectrum; Nev11121; pectin
      12. Abstract :
        BACKGROUND: Semi-solidification by gelation or increased viscosity could slow the influx of liquid enteral nutrition (EN) into the small intestine. A liquid EN formula containing pectin that gels under acidic conditions such as those found in the stomach has been developed. A new near-infrared fluorescent imaging reagent was used to non-invasively acquire real time images of gastric emptying in a murine model in vivo. We postulated that the EN formula delays gastric emptying and tested this hypothesis using imaging in vivo.
        METHODS: Male BALB/c mice were given an oral bolus injection of a liquid EN containing the fluorescence reagent GastroSense750 with or without pectin. The EN in the stomach was visualized in vivo at various intervals using a non-invasive live imaging system and fluorescent signals were monitored from the stomach, which was removed at 60 min after EN ingestion.
        RESULTS: The fluorescence intensity of signals in stomachs in vivo and in resected stomachs was lower and attenuated over time in mice given EN without, than with pectin.
        CONCLUSIONS: Adding a gelling agent such as pectin delayed the transit of liquid EN from the stomach. Fluorescence imaging can visualize the delayed gastric emptying of EN containing pectin.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/25263497
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        11641
      1. Author :
        Lin, S. A.; Patel, M.; Suresch, D.; Connolly, B.; Bao, B.; Groves, K.; Rajopadhye, M.; Peterson, J. D.; Klimas, M.; Sur, C.; Bednar, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Mol Imaging
      6. Products :
      7. Volume :
        2012
      8. Issue :
        N/A
      9. Page Numbers :
        189254
      10. Research Area :
        N/A
      11. Keywords :
        FMT, Prosense, CatB, Cathepsin B, fluorescence imaing, tomography, microCT
      12. Abstract :
        Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of alpha(v)beta(3) integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using cathepsin sensing (ProSense, CatB FAST) and alpha(v)beta(3) integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE(-/-) mice (P < 0.05) versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7 mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated (P < 0.05) versus untreated apoE(-/-) mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and alpha(v)beta(3) integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23119157
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10571
      1. Author :
        Vandamme, M.; Robert, E.; Lerondel, S.; Sarron, V.; Ries, D.; Dozias, S.; Sobilo, J.; Gosset, D.; Kieda, C.; Legrain, B.; Pouvesle, J. M.; Pape, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Int J Cancer
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        U87-MG-luc2, U-87-MG-luc2, U87MG-luc2, Bioluminescence, Glioma, IVIS
      12. Abstract :
        Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21702038
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10424
      1. Author :
        Subbarayan, P. R.; Sarkar, M.; Nagaraja Rao, S.; Philip, S.; Kumar, P.; Altman, N.; Reis, I.; Ahmed, M.; Ardalan, B.; Lokeshwar, B. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Ethnopharmacol
      6. Products :
      7. Volume :
        142
      8. Issue :
        N/A
      9. Page Numbers :
        523-30
      10. Research Area :
        N/A
      11. Keywords :
        BxPC-3, BxPC-3-luc2, IVIS, Achyranthes; Animals; Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use; Apoptosis/*drug effects; Caspase 3/genetics/metabolism; Gene Expression/drug effects; Humans; Injections, Intraperitoneal; Medicine, Ayurvedic; Mice; Mice, Nude; Pancreatic Neoplasms/*drug therapy/genetics/metabolism; Phosphorylation; *Phytotherapy; Plant Extracts/pharmacology/*therapeutic use; Plant Leaves; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/metabolism; Xenograft Model Antitumor Assays
      12. Abstract :
        ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes aspera (Family Amaranthacea) is used for cancer therapy by ayurvedic medical practitioners in India. However, due to the non formal nature of its use, there are no systematic studies validating its medicinal properties. Thus, it's utility as an anti cancer agent remains anecdotal. Earlier, we demonstrated A. aspera to exhibit time and dose-dependent preferential cytotoxicity to cultured human pancreatic cancer cells. In this report we validate in vivo anti tumor properties of A. aspera. MATERIALS AND METHODS: The in vivo anti tumor activity of leaf extract (LE) was tested by intraperitoneal (IP) injections into athymic mice harboring human pancreatic tumor subcutaneous xenograft. Toxicity was monitored by recording changes in behavioral, histological, hematological and body weight parameters. RESULTS: Dosing LE to athymic mice by I.P. injection for 32 days showed no adverse reactions in treated mice. Compared to the control set, IP administration of LE to tumor bearing mice significantly reduced both tumor weight and volume. Gene expression analysis using Real time PCR methods revealed that LE significantly induced caspase-3 mRNA (p<0.001) and suppressed expression of the pro survival kinase Akt-1 (p<0.05). TUNEL assay and immunohistochemistry confirmed apoptosis induction by activation of caspase-3 and inhibiting Akt phosphorylation in treated sets. These results are in agreement with RT PCR data. CONCLUSION: Taken together, these data suggest A. aspera to have potent anti cancer property.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22640722
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10484
      1. Author :
        Chen, J.; Gallo, K. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        4130-40
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc2-tdtomato, IVIS, tdtomato, fluorescent protein, Animals; Breast Neoplasms/enzymology/*metabolism/*pathology; Cell Line, Tumor; Cell Movement/*physiology; Chemokine CXCL12/metabolism; Female; Humans; MAP Kinase Kinase Kinases/*metabolism; MAP Kinase Signaling System; Mice; Mice, Nude; Neoplasm Invasiveness; Paxillin/*metabolism; Phosphorylation
      12. Abstract :
        MLK3 kinase activates multiple mitogen-activated protein kinases and plays a critical role in cancer cell migration and invasion. In the tumor microenvironment, prometastatic factors drive breast cancer invasion and metastasis, but their associated signaling pathways are not well-known. Here, we provide evidence that MLK3 is required for chemokine (CXCL12)-induced invasion of basal breast cancer cells. We found that MLK3 induced robust phosphorylation of the focal adhesion scaffold paxillin on Ser 178 and Tyr 118, which was blocked by silencing or inhibition of MLK3-JNK. Silencing or inhibition of MLK3, inhibition of JNK, or expression of paxillin S178A all led to enhanced Rho activity, indicating that the MLK3-JNK-paxillin axis limits Rho activity to promote focal adhesion turnover and migration. Consistent with this, MLK3 silencing increased focal adhesions and stress fibers in breast cancer cells. MLK3 silencing also decreased the formation of breast cancer lung metastases in vivo, and breast cancer cells derived from mouse lung metastases showed enhanced Ser 178 paxillin phosphorylation. Taken together, our findings suggest that the MLK3-JNK-paxillin signaling axis may represent a potential therapeutic target and/or prognostic marker in breast cancer metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22700880
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10495
      1. Author :
        Phillips, W. T.; Goins, B.; Bao, A.; Vargas, D.; Guttierez, J. E.; Trevino, A.; Miller, J. R.; Henry, J.; Zuniga, R.; Vecil, G.; Brenner, A. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Neuro Oncol
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        416-25
      10. Research Area :
        N/A
      11. Keywords :
        U-87 MG-luc2, U-87-MG-luc2, Glioma, Bioware, IVIS, Animals; Brachytherapy/*methods; Brain Neoplasms/pathology/*radiotherapy; Convection; Glioblastoma/pathology/*radiotherapy; Glioma/pathology/*radiotherapy; Liposomes; Nanoparticles/therapeutic use; Radioisotopes/*therapeutic use; Rats; Rhenium/*therapeutic use; Tumor Burden; Xenograft Model Antitumor Assays
      12. Abstract :
        Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ((186)Re)-liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of (186)Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 microL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with (186)Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4-173 days), compared with 49 days (95% CI, 44-53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (chi(2)[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (chi(2)[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by (186)Re-liposomes convection-enhanced delivery in glioma.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22427110
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10500
      1. Author :
        Oashi, K.; Furukawa, H.; Nishihara, H.; Ozaki, M.; Oyama, A.; Funayama, E.; Hayashi, T.; Kuge, Y.; Yamamoto, Y.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Invest Dermatol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        B16-F10-luc2, Melanoma, B16F10-luc2, IVIS
      12. Abstract :
        In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor dissemination, characterized by the presence of melanoma cells between the primary lesion and the draining regional lymph node basin that is clinically associated with poor prognosis. In this study, we aimed to establish an experimental animal model of melanoma ITM, as research progress in this field has been hampered by a lack of suitable experimental models. We reproduced melanoma ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a mouse with lymphedema (LE). The tumor cells at the ITM site were highly proliferative, and mice with ITMs were more likely than control mice to develop distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor-associated blood vessels were increased in the primary tumor site of the LE mice. Our established ITM melanoma mouse model enabled us to clarify the molecular determinants and pathophysiology of ITM. This ITM model is also comparable to the unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined the importance of lymphangiogenic factors in the tumor dissemination through the lymphatic system.Journal of Investigative Dermatology advance online publication, 6 September 2012; doi:10.1038/jid.2012.274.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22951727
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10501
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