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      1. Author :
        Laurie E. Littlepage; Mark D. Sternlicht; Nathalie Rougier; Joanna Phillips; Eugenio Gallo; Ying Yu; Kurt Williams; Audrey Brenot; Jeffrey I. Gordon; Zena Werb
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Research
      6. Products :
      7. Volume :
        70
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        matrix metalloproteinase; neuroendocrine; prostate cancer; metatasis
      12. Abstract :
        Prostate cancer is the leading form of cancer in men. Prostate tumors often contain neuroendocrine differentiation, which correlates with androgen-independent progression and poor prognosis. Matrix metalloproteinases (MMP), a family of enzymes that remodel the microenvironment, are associated with tumorigenesis and metastasis. To evaluate MMPs during metastatic prostatic neuroendocrine cancer development, we used transgenic mice expressing SV40 large T antigen in their prostatic neuroendocrine cells, under the control of transcriptional regulatory elements from the mouse cryptdin-2 gene (CR2-TAg). These mice have a stereotypical pattern of tumorigenesis and metastasis. MMP-2, MMP-7, and MMP-9 activities increased concurrently with the transition to invasive metastatic carcinoma, but they were expressed in different prostatic cell types: stromal, luminal epithelium, and macrophages, respectively. CR2-TAg mice treated with AG3340/Prinomastat, an MMP inhibitor that blocks activity of MMP-2, MMP-9, MMP-13, and MMP-14, had reduced tumor burden. CR2-TAg animals were crossed to mice homozygous for null alleles of MMP-2, MMP-7, or MMP-9 genes. At 24 weeks CR2-TAg; MMP-2-/- mice showed reduced tumor burden, prolonged survival, decreased lung metastasis, and decreased blood vessel density, whereas deficiencies in MMP-7 or MMP-9 did not influence tumor growth or survival. Mice deficient for MMP-7 had reduced endothelial area coverage and decreased vessel size, and mice lacking MMP-9 had increased numbers of invasive foci and increased perivascular invasion, as well as decreased tumor blood vessel size. Together, these results suggest distinct contributions by MMPs to the progression of aggressive prostate tumor and to helping tumors cleverly find alternative routes to malignant progression.
      13. URL :
        http://cancerres.aacrjournals.org/content/70/6/2224.abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4490
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        angiogenesis imaging; in vivo imaging; Angiogenesis; Bioluminescence; Fluorescence; Molecular imaging; Optical imaging
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911541/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4488
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Molecular Imaging and Biology
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Optical imaging, Image-guided surgery, Molecular imaging, Near-infrared fluorescence
      12. Abstract :
        In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-tobackground-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.
      13. URL :
        http://www.springerlink.com/content/78233815221t6563/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4486
      1. Author :
        J-C Tseng; T Granot; V DiGiacomo; B Levin; D Meruelo
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Gene Therapy
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Sindbis virus; viral vector; vascular leakiness; molecular imaging; chemotherapy; cancer
      12. Abstract :
        Genetic instability of cancer cells generates resistance after initial responses to chemotherapeutic agents. Several oncolytic viruses have been designed to exploit specific signatures of cancer cells, such as important surface markers or pivotal signaling pathways for selective replication. It is less likely for cancer cells to develop resistance given that mutations in these cancer signatures would negatively impact tumor growth and survival. However, as oncolytic viral vectors are large particles, they suffer from inefficient extravasation from tumor blood vessels. Their ability to reach cancer cells is an important consideration in achieving specific oncolytic targeting and potential vector replication. Our previous studies indicated that the Sindbis viral vectors target tumor cells by the laminin receptor. Here, we present evidence that modulating tumor vascular leakiness, using VEGF and/or metronomic chemotherapy regimens, significantly enhances tumor vascular permeability and directly enhances oncolytic Sindbis vector targeting in tumor models. Because host-derived vascular endothelium cells are genetically stable and less likely to develop resistance to chemotherapeutics, a combined metronomic chemotherapeutics and oncolytic vector regimen should provide a new approach for cancer therapy. This mechanism could explain the synergistic treatment outcomes observed in clinical trials of combined therapies.
      13. URL :
        http://www.nature.com/cgt/journal/v17/n4/full/cgt200970a.html
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4485
      1. Author :
        Rahul Anil Sheth; Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        American Journal of Physiology: Gastrointestinal and Liver Physiology
      6. Products :
      7. Volume :
        299
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Colorectal cancer; optical imaging; molecular imaging; cancer genetics
      12. Abstract :
        Colorectal cancer remains a major cause of morbidity and mortality in the United States. The advent of molecular therapies targeted against specific, stereotyped cellular mutations that occur in this disease has ushered in new hope for treatment options. However, key questions regarding the optimal dosing schedules, dosing duration, and patient selection remain unanswered. In this review, we describe how recent advances in molecular imaging, specifically optical molecular imaging with fluorescent probes, offer potential solutions to these questions and may play a key role in improving outcomes. We begin with an overview of optical molecular imaging, including a discussion on the various methods of design for fluorescent probes and the clinically relevant imaging systems that have been built to image them. We then focus on the relevance of optical molecular imaging to colorectal cancer. We review the most recent data on how this imaging modality has been applied to the measurement of treatment efficacy for currently available as well as some as-of-yet developmental molecularly targeted therapies in animal studies. We then conclude with a discussion on how this imaging approach has already begun to be translated clinically for human use.
      13. URL :
        http://ajpgi.physiology.org/cgi/content/abstract/ajpgi.00195.2010v1
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4484
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