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| 1 | Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody显示文摘AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer. | Winn Aung Atsushi B Tsuji Aya Sugyo Hiroki Takashima Masahiro Yasunaga Yasuhiro Matsumura Tatsuya Higashi | 2018 | World Journal of Gastroenterology2018，24，48： | 7 |
| 2 | The effect of mental effort on open- and close-loop accommodation 显示文摘 | Winn B Gihnartin B Montimer LC | 1991 | Ophthalmic Physiol Opt1991，11，： | 1 |
| 3 | A Tool for Safety Professionals and Design Engineers 显示文摘 | Gary L Winn B Gopalakrishnan Magdy Akladios | 2002 | Professional Safety2002，，10： | 1 |
| 4 | Market imperfections, opportunity and sustainable entrepreneurship 显示文摘 | Cohen B Winn M | 2007 | Journal of Business Venturing2007，22，1： | 1 |
| 5 | Hyperglycemia and neurologic outcome in patient with head injury显示文摘 | LAM A M WINN H R CULLEN B F | 1991 | J Neurosurg1991，75，4： | 1 |
| 6 | Market imperfections, opportunity and sustainable entrepreneurship显示文摘 | COHEN B WINN M I | 2007 | Journal of Business Venturing2007，，1： | 1 |
| 7 | The multifocal visual evoked potential显示文摘 | Hood D C Odel J G Winn B J | 2003 | Journal of Neuro-Ophthalmology2003，23，4： | 1 |
| 8 | Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2in poorly differentiated colorectal carcinomas显示文摘 | Winn B Tavares R Matoso A | 2010 | Hum Pathol2010，41，1： | 1 |
| 9 | Dynamic effects of bang-bang control on the thermal performance walls of various constructions 显示文摘 | Bums P J Han K Winn C B | 1991 | Energy1991，46，3： | 1 |
| 10 | Nearwork induced transient myopia during myopia progression 显示文摘 | Vera-Diaz FA Strang NC Winn B | 2002 | Curr Eye Res2002，24，4： | 1 |
| 11 | The effect of mental effort on open-and closed-loop accommodation显示文摘 | Winn B Gilmartin B Mortimer LC | 1991 | Ophthalmic Physiol Opt1991，11，4： | 1 |
| 12 | Phase Ⅱ trial of carboplatin plus cisplatin in recurrent and advanced squamous cell carcinoma of the head and neck 显示文摘 | Dimery IW Brooks B J Winn R | 1991 | J Clin Oncol1991，9，11： | 1 |
| 13 | Market imperfections, opportunity and sustainable entrepreneurship显示文摘 | Cohen B Winn M | 2007 | Journal of Business Vent- uring2007，22，1： | 1 |
| 14 | Power spectrum analysis in the study of ocular mechanisms 显示文摘 | Pugh JR Eadie AS Winn B | 1987 | Ophthalmic Physiol Opt1987，7，3： | 1 |
| 15 | Effect of target luminance on microfluctuations of accommodation 显示文摘 | GRAY LS WINN B GILMARTIN B | 1993 | Ophthalmic Physiol Opt1993，13，3： | 1 |
| 16 | Nearwork induced transient myopia during myopia progression 显示文摘 | VERA-DIAZ FA STRANG NC WINN B | 2002 | Curr Eye Res2002，24，4： | 1 |
| 17 | Nearwork induced transi-ent myopia during myopia progression 显示文摘 | Vera-Dias F A Strang N C Winn B | 2002 | Curr Eye Res2002，24，2： | 1 |
| 18 | Nearwork induced transient myopia during myopia progression显示文摘 | Vera-Diaz FA Strang NC Winn B | 2002 | Curr Eye Res2002，24，4： | 1 |
| 19 | Optimal dispatch strategy in remote hybrid power systems显示文摘 | Barley C D Winn C B | 1996 | Solar Energy1996，58，4： | 1 |
| 20 | Organizational quality: An exami- nation of the Malcolm Baldrige quality framework 显示文摘 | Winn B A Cameron K S | 1998 | Re- search in Higher Education1998，39，5： | 1 |
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