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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 | Apoptosis observable in peripheral T lymphocytes from patients with chronic hepatitis B显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，1： | 1 |
| 3 | Apoptosis Observed in Peripheral T Lymphocytes Observed in Peripheral T Lymphocytes from Patients with Chronic Hepatitis B显示文摘 | Yuh K Sugyo S | 1996 | Gastroenterology1996，111，： | 1 |
| 4 | Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B 显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，1： | 1 |
| 5 | Apoptosis oberserved in peripheral T lymphocytes form patients with chronic hepatitis B显示文摘 | YUH K SUGYO S | 1996 | Gastroenterology1996，111，1： | 1 |
| 6 | Apoptosis observed in peripheral T lymphocytes from patients with chronichepatitis B显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，1： | 1 |
| 7 | Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B显示文摘 | NAKAMURA K YUH K SUGYO S | 1996 | Gastroenterology1996，111，： | 1 |
| 8 | Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B显示文摘 | NAKAMURA K YUH K SUGYO S | 1996 | Gastroenterology1996，111，1： | 1 |
| 9 | Apoptosis observed in peripheral T lymphocytes from patients with patients with chronic hepatitis B显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，1： | 1 |
| 10 | Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，： | 1 |
| 11 | Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse model显示文摘 | Sudo H Tsuji AB Sugyo A | 2010 | Genomics2010，95，4： | 1 |
| 12 | Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B 显示文摘 | Nakamura K Yuh K Sugyo S | 1996 | Gastroenterology1996，111，1： | 1 |
| 13 | Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts显示文摘 | Atsushi B. Tsuji Chizuru Sogawa Aya Sugyo Hitomi Sudo Jun Toyohara Mitsuru Koizumi Masaaki Abe Okio Hino Yoshi-nobu Harada Takako Furukawa Kazutoshi Suzuki Tsuneo Saga | 2009 | Nuclear Medicine and Biology2009，，4： | 1 |
| 14 | Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/m TOR inhibitor显示文摘AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm alone.RESULTS We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2 AX-positive cells and decreased p-4 EBP1 expression. CONCLUSION The therapeutic efficacy of ^(90) Y-ITGA6 B4-RIT can be improved by combining with dual PI3 K and m TOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application. | Winn Aung Atsushi B Tsuji Hitomi Sudo Aya Sugyo Yoshinori Ukai Katsushi Kouda Yoshikazu Kurosawa Takako Furukawa Tsuneo Saga Tatsuya Higashi | 2017 | World Journal of Gastroenterology2017，23，42： | 0 |
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