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  • American Association for Cancer Research (AACR)  (3)
  • Kobayashi, Hisataka  (3)
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  • American Association for Cancer Research (AACR)  (3)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4332-4332
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4332-4332
    Abstract: Word limit: 2600 characters, including abstract body and title. Optical imaging has the potential to become a robust tool in intraoperative sentinel lymph node mapping because of its portability, high spatial resolution, and absence of radiation. Most preclinical and clinical studies have used conventional fluorescent agents, which need excitation light to emit fluorescence. However, excitation light also induces autofluorescence (background signal) from intrinsic fluorophores in the normal tissue, lowering the target-to-background ratio. We developed two new methods for optical sentinel lymph node mapping to eliminate background signals using two unique nano-particles; an upconverting nano-particle (UCNP) and a self-illuminating bioluminescence resonance energy transfer quantum-dot (BRET-QD) nano-particle. UCNPs are unique nano-sized particles that emit light at shorter wavelengths with excitation in the near infrared (NIR). Since fluorophores typically emit light at longer wavelengths than the excitation light, there is no autofluorescence. Moreover, by changing the composition of the doping metals, UCNPs can be designed to emit at specific wavelengths. When UCNPs were injected into the chin of anesthetized mice, and excited at 950-nm, superficial neck lymph nodes were successfully depicted with no background signals in the visible-range (peak 550 nm) or NIR-range (peak 800 nm) in all mice. Furthermore, with serial injection of the visible and NIR-range UCNPs, simultaneous lymphatic imaging was achieved in two colors. The BRET-QD is self-illuminating and employs the substrate, coelenterazine, which reacts with luciferase conjugated on the BRET-QD. The bioluminescent light in blue efficiently excites the NIR QD, and emits photons in the NIR, therefore, there is no autofluorophore excitation. Moreover, by changing the QDs within BRET-QD, it is possible to alter their emission wavelength. BRET-QD655, (QD655 in its core), was injected at different sites (chin, ear, forepaws, and hind paws) of anesthetized mice. After BRET-QD655 injection, coelenterazine was intravenously injected and imaging was performed without excitation light. In all mice, sentinel lymph nodes in each lymphatic basin were clearly visualized with ultra-low background signals, and lasted at least 30 min after coelenterazine injections. In conclusion, we demonstrate that optical imaging using two unique nano-particles were able to depict sentinel lymph nodes with minimal autofluorescence. This enables the direct, real time sentinel lymph node mapping without extensive post processing of the images. These two novel nano-particles have the potential to be robust tools for sentinel lymph node detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4332.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3618-3618
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3618-3618
    Abstract: Three modes of cancer therapy, surgery, radiation and chemotherapy, have been central to modern oncologic therapy. Molecular targeted cancer therapies have been introduced to target specific pathways, while minimizing side effects but have had limited success except in several notable cases. The concept of amplifying the effect of molecular targeting by applying physical energy to the bound conjugate is relatively new. In this study, we describe a hydrophilic photosensitizer based on a near infrared (NIR) phthalocyanine dye, IR700, which is covalently conjugated to one of several humanized monoclonal antibodies (MAb) targeting human epidermal growth factor receptor (EGFR) type 1 (HER1) and 2 (HER2). When exposed to light the conjugate induces highly selective cell death in vivo, a process termed “photo-activatable immunotherapy” (PIT). In vitro studies were conducted with Trastuzumab-IR700 bound to HER2-expressing NIH3T3 cells (3T3/HER2) and panitumumab-IR700 bound to HER1-expressing A431 cells which were then irradiated with non harmful NIR light. EGFR-negative Balb3T3 cells were used as controls. In vivo studies were conducted with 3T3/HER2 and A431 xenograft tumors 1 day after intravenous administration of MAb-IR700 followed by non harmful, transcutaneous NIR light. MAb-IR700 demonstrated specific binding to target receptors on the cell membrane, which was followed by gradual internalization into endolysosomal compartments. MAb-IR700 bound target-specific cell death could be induced within 5 minutes of exposure to NIR light and resulted in cellular swelling, bleb formation, and rupture of vesicles indicating necrotic cell death. No phototoxicity was observed in co-cultured receptor-negative Balb3T3 cells after incubation with MAb-IR700, even when MAb-IR700 was not removed from the medium during light exposure. EGFR target-specific accumulation of MAb-IR700 was observed in the mouse xenograft tumors on NIR fluorescence images. Greater than 90% tumor shrinkage within 3 days of the NIR irradiation, was measured, with no apparent side effects, but was only observed in EGFR-expressing tumors. Furthermore, IR700 fluorescence produced by the MAb conjugate permitted guidance of light delivery and allowed for monitoring after therapy. The MAb-IR700 PIT was most effective, when conjugates were bound to the cell membrane, but showed no phototoxicity, when unbound, suggesting a novel mechanism for PIT compared with conventional photodynamic therapies. Target selective PIT based on MAb-IR700 conjugate membrane binding enables selective treatment of cancer with no apparent side effect to normal cells or surrounding tissue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2011-3618
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 3
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 4, No. 5 ( 2011-05-01), p. 767-773
    Abstract: Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Vaccines for HPV infection can reduce the risk of developing cervical cancer. To further improve such vaccines and to explore other methods of preventing or treating viral infection, longitudinal studies in experimental animals are desirable. Here, we describe a newly developed multicolor endoscopic fluorescence imaging system to visualize early HPV infection with fluorescent protein–encoded pseudoviruses (PsV) in the female genital tract of living mice. With this imaging method, the course of HPV PsV infection and the effects of intervention to prevent infection can be monitored in a single mouse over time. Female immunocompetent or athymic mice were pretreated with a vaginal spermicide and then HPV PsV composed of an authentic viral capsid and encapsidating green or red fluorescent protein (GFP or RFP) reporter gene was intravaginally instilled. Expression of GFP or RFP was detected 1 day after PsV challenge, which peaked after 2 or 3 days and decreasing thereafter. No fluorescence was detected in vaccine-treated immunocompetent mice. By using serial infection of the same PsV type (HPV16) encoding either GFP or RFP, different infection patterns of repeated exposure can be monitored. This method offers the ability to monitor experimental virus infections before and after intervention, thereby accelerating the development of appropriate prevention and therapy. Cancer Prev Res; 4(5); 767–73. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2422346-3
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