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      1. Author :
        Akudugu, J. M.; Azzam, E. I.; Howell, R. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Radiat Biol
      6. Products :
      7. Volume :
        88
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer
      12. Abstract :
        Abstract Purpose: This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with (125)I-labeled 5-iodo-2 -deoxyuridine ((125)IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods: In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix carbon scaffold. Cultures were pulse-labeled for 3 h with (125)IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2'-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT((R)) EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with (125)IdU/EdU. Additional aliquots were used to determine the mean (125)I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results: Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions: These studies demonstrate the capacity of (125)IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22489958
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10514
      1. Author :
        Hamrahi, V.; Hamblin, M. R.; Jung, W.; Benjamin, J. B.; Paul, K. W.; Fischman, A. J.; Tompkins, R. G.; Carter, E. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Interdiscip Perspect Infect Dis
      6. Products :
      7. Volume :
        2012
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen44, Xen 44, Proteus mirabilis, bioluminescence imaging
      12. Abstract :
        Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22899912
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10562
      1. Author :
        Qingbei Zhang; Meng Yang; Jikun Shen; Lynnette M. Geerhold; Robert M Hoffman; H. Rosie Xing
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        International Journal of Cancer
      6. Products :
      7. Volume :
        126
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        metastasis; hemotogenous spread; prostate cancer; GFP; in vivo imaging
      12. Abstract :
        Metastasis is primarily responsible for the morbidity and mortality of cancer. Improved therapeutic outcomes and prognosis depend on improved understanding of mechanisms regulating the establishment of early metastasis. In this study, use of green fluorescent protein (GFP)-expressing PC-3 orthotopic model of human prostate cancer and two complementary fluorescence in vivo imaging systems (Olympus OV100 and VisEn FMT) allowed for the first time real-time characterization of cancer cell-endothelium interactions during spontaneous metastatic colonization of the liver and lung in live mice. We observed that prior to the detection of extra-vascular metastases, GFP-expressing PC-3 cancer cells resided initially inside the blood vessels of the liver and the lung, where they proliferated and expressed Ki-67 and exhibited matrix metalloprotenases (MMP) activity. Thus, the intravascular cancer cells produced their own microenvironment, where they could continue to proliferate. Extravasation occurred earlier in the lung than in the liver. Our results demonstrate that the intravascular microenvironment is a critical staging area for the development of metastasis that later can invade the parenchyma. Intravascular tumor cells may represent a therapeutic target to inhibit the development of extravascular metastases. Therefore, this imageable model of intravascular metastasis may be used for evaluation of novel anti-metastatic agents.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1002/ijc.24979/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4493
      1. Author :
        Sharma, Praveen K; Singh, Rajesh; Novakovic, Kristian R; Eaton, John W; Grizzle, William E; Singh, Shailesh
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International journal of cancer. Journal international du cancer
      6. Products :
      7. Volume :
        127
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Apoptosis; Bioware; Caspase 3; Cell Line, Tumor; Chemokines, CC; Disease Progression; Enzyme Activation; Etoposide; Humans; Male; Mice; Mice, Nude; PC-3M-luc; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, CCR; Signal Transduction
      12. Abstract :
        Despite recent advances in treatment and management of prostate cancer (PCa), it remains the second leading cause of cancer-related deaths among men in the US. Chemotherapy is one of the treatment alternatives for hormone refractory metastatic PCa. However, current chemotherapeutic regimens provide palliative benefit but relatively modest survival advantage primarily due to chemo-resistance and upregulated antiapoptotic machineries in PCa cells. Therefore, blocking the mechanisms responsible for suppression of apoptosis might improve current chemotherapeutic regimens. In this study, we show that CC chemokine receptor-9 (CCR9) and its natural ligand CCL25 interaction upregulates antiapoptotic proteins (i.e., PI3K, AKT, ERK1/2 and GSK-3beta) and downregulate activation of caspase-3 in PCa cells. Significant downregulation of these CCR9-mediated antiapoptotic proteins in the presence of a PI3K inhibitor (wortmannin), further suggests that the antiapoptotic action of CCR9 is primarily regulated through PI3K. Furthermore, the cytotoxic effect of etoposide was significantly inhibited in the presence of CCL25, and this inhibitory effect of CCL25 was abrogated when CCR9-CCL25 interaction was blocked using anti-CCR9 monoclonal antibodies. In conformation to these in vitro studies, significant reduction in tumor burden was found in mice receiving CCL25 neutralizing antibodies and etoposide together as compared to both as a single agent. These results suggest that the CCR9-CCL25 axis mediates PI3K/AKT-dependent antiapoptotic signals in PCa cells and could be a possible reason for low apoptosis and modest chemotherapeutic response. Therefore, targeting CCR9-CCL25 axis with cytotoxic agents may provide better therapeutic outcomes than using cytotoxic agents alone.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20127861
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8945
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International Journal of Cardiovascular Imaging
      6. Products :
      7. Volume :
        26
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Cardiovascular disease; Atherosclerosis; Vulnerable plaque; Spectroscopy; Intravascular; in vivo imaging; MMPSense
      12. Abstract :
        Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.
      13. URL :
        http://www.springerlink.com/content/kx38073782g98666/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4552
      1. Author :
        Ackermann, M.; Carvajal, I.M.; Morse, B.A.; Moreta, M.; O'Neil, S.; Kossodo, S.; Peterson, J.D.; Delventhal, V.; Marsh, H.N.; Furfine, E.S.; Konerding, M.A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        International Journal of Oncology
      6. Products :
      7. Volume :
        38
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; anti-angiogenic; anti-tumorigenic; Cancer; FMT1 (VisEn); FMT-Solaris; In vivo imaging (VisEn); intraperitoneal injection; mice
      12. Abstract :
        Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin[TM], CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human fibronectin. CT-322 treated tumors exhibited a significant reduction in tumor growth of 69%, a 2.8 times lower tumor surface area and fewer necrotic areas. Control tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in CT-322-treated tumors was characterized by a strong normalization of vasculature. This was quantified in corrosion casts of CT-322 treated tumors in which the intervascular distance (a reciprocal parameter indicative of vessel density) and the distance between two consecutive branchings were assessed, with these distances being 2.21 times and 2.37 times greater than in controls, respectively. Fluorescence molecular tomography (FMT) equally affirmed the inhibitory effects of CT-322 on tumor vasculature as indicated by a 60% reduction of the vascular probe, AngioSense, accumulating in tumor tissue, as a measurement of vascular permeability. Moreover, AngioSense accumulation was reduced as early as 24 h after starting treatment. The sum of these effects on tumor vasculature illustrates the anti-angiogenic mechanism underlying the antitumor activity of CT-322 and provides support for further evaluation of this Adnectin in combinatorial strategies with standard of care therapies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21109927
      14. Call Number :
        PKI @ user @ 8449
      15. Serial :
        4804
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