Photoimmunotherapy Inhibits Tumor Recurrence After Surgical Resection on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model.

Photoimmunotherapy Inhibits Tumor Recurrence After Surgical Resection on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model.
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DOI:
10.1245/s10434-015-4553-9
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发表时间:
2015-12
影响因子:
3.7
通讯作者:
Bouvet M
Bouvet M
中科院分区:
医学2区
文献类型:
--
作者:
Hiroshima Y;Maawy A;Zhang Y;Guzman MG;Heim R;Makings L;Luiken GA;Kobayashi H;Tanaka K;Endo I;Hoffman RM;Bouvet M

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光免疫疗法(PIT)使用基于近红外(NIR)酞菁染料IR 700的靶向特异性光敏剂,在用NIR光照射后诱导肿瘤坏死,以杀死癌细胞,例如手术后残留的癌细胞。本研究的目的是在表达癌胚抗原(CEA)的患者源性原位异种移植(PDOX)裸鼠模型中使用PIT对胰腺癌切除术后的手术床进行消毒。在确认肿瘤植入后,将小鼠随机分为两组:仅明亮光手术(BLS)和BLS + PIT。每个治疗组由7只荷瘤小鼠组成。在标准明视野下用MVX 10长工作距离、高放大倍数显微镜对所有小鼠进行BLS。对于BLS + PIT,在手术前24小时向所有小鼠静脉注射与IR 700偶联的抗CEA抗体(抗CEA-IR 700)(50 μg)。手术后,用690 ± 5 nm的红色发光二极管以150 mW/cm 2的功率密度照射切除床。抗CEA-IR 700标记并照亮胰腺癌PDOX。在BLS后通过荧光检测PDOX的最小残留癌。仅BLS处理的小鼠的局部复发率为85.7%,BLS + PIT处理的小鼠的局部复发率为28.6%(p = 0.05)。仅BLS处理的小鼠的平均复发肿瘤重量为1149.0 ± 794.6 mg,BLS + PIT处理的小鼠的平均复发肿瘤重量为210.8 ± 336.9 mg(p = 0.015)。抗CEA-IR 700能够标记和照亮胰腺癌PDOX裸鼠模型,足以用于PIT。PIT通过消除BLS后残留的癌细胞来减少复发。
Photoimmunotherapy (PIT) uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, to induce tumor necrosis after irradiation with NIR light to kill cancer cells, such as those that remain after surgery. The purpose of the present study was to sterilize the surgical bed after pancreatic cancer resection with PIT in carcinoembryonic antigen (CEA)-expressing, patient-derived, orthotopic xenograft (PDOX) nude mouse models. After confirmation of tumor engraftment, mice were randomized to two groups: bright light surgery (BLS)-only and BLS + PIT. Each treatment arm consisted of seven tumor-bearing mice. BLS was performed under standard bright-field with an MVX10 long-working distance, high-magnification microscope on all mice. For BLS + PIT, anti-CEA antibody conjugated with IR700 (anti-CEA-IR700) (50 μg) was injected intravenously in all mice 24 h before surgery. After the surgery, the resection bed was then irradiated with a red-light-emitting diode at 690 ± 5 nm with a power density of 150 mW/cm2. Anti-CEA-IR700 labelled and illuminated the pancreatic cancer PDOX. Minimal residual cancer of the PDOX was detected by fluorescence after BLS. The local recurrence rate was 85.7 % for BLS-only and 28.6 % for BLS + PIT-treated mice (p = 0.05). The average recurrent tumor weight was 1149.0 ± 794.6 mg for BLS-only and 210.8 ± 336.9 mg for BLS + PIT-treated mice (p = 0.015). Anti-CEA-IR700 was able to label and illuminate a pancreatic cancer PDOX nude mouse model sufficiently for PIT. PIT reduced recurrence by eliminating remaining residual cancer cells after BLS.
DOI: 10.1073/pnas.89.12.5645
发表时间: 1992-06-15
影响因子: 11.1
作者:
FU, XY;GUADAGNI, F;HOFFMAN, RM
通讯作者: HOFFMAN, RM
DOI: 10.1002/jso.2930470303
发表时间: 1991-07-01
影响因子: 2.5
作者:
YAMAGUCHI, K;ENJOJI, M;TSUNEYOSHI, M
通讯作者: TSUNEYOSHI, M
DOI: 10.1073/pnas.88.20.9345
发表时间: 1991-10-01
影响因子: 11.1
作者:
FU, XY;BESTERMAN, JM;HOFFMAN, RM
通讯作者: HOFFMAN, RM
DOI: 10.1038/nm.2554
发表时间: 2011-11-06
期刊: Nature medicine
影响因子: 82.9
作者:
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DOI: 10.1371/journal.pone.0117417
发表时间: 2015
期刊: PloS one
影响因子: 3.7
作者:
Hiroshima Y;Zhang Y;Zhang N;Maawy A;Mii S;Yamamoto M;Uehara F;Miwa S;Yano S;Murakami T;Momiyama M;Chishima T;Tanaka K;Ichikawa Y;Bouvet M;Murata T;Endo I;Hoffman RM
通讯作者: Hoffman RM