Background/Aims Laparoscopy is important in staging pancreatic cancer, but false negatives remain problematic. Making tumors fluorescent has the potential to improve the accuracy of staging laparoscopy. Methodology Orthotopic and carcinomatosis models of pancreatic cancer were established with BxPC-3 human pancreatic cancer cells in nude mice. Alexa488-anti-CEA conjugates were injected via tail vein 24 hours prior to laparoscopy. Mice were examined under bright field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes measured included time to identification of primary tumor for the orthotopic model and number of metastases identified within 2 minutes for the carcinomatosis model. Results FL enabled more rapid and accurate identification and localization of primary tumors and metastases than BL. Using BL took statistically significantly longer time than FL. More metastatic lesions were detected and localized under FL compared to BL and with greater accuracy, with sensitivities of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough to detect metastatic lesions <1mm. Conclusions The use of fluorescence laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody permits rapid detection and accurate localization of primary and metastatic pancreatic cancer in an orthotopic model. The results of the present report demonstrate the future clinical potential of fluorescence laparoscopy.
There is a strong association between poor survival and increased macrophage density in many cancers. In the current study, we determined whether macrophages from tumor-bearing mice (tumor-educated macrophages) had greater tumor-promoting capability than macrophages from non-tumor-bearing mice. Ten transgenic nude mice ubiquitously-expressing GFP were injected subcutaneously with the human pancreatic cancer cell line, BXPC3 stably expressing RFP. GFP-expressing macrophages from tumor-bearing transgenic GFP mice were harvested and defined as “tumor-educated macrophages”. Macrophages were also harvested from transgenic GFP mice (n=10) without subcutaneous tumors and identified as “naïve macrophages.” Three groups of mice were studied: 1) A control group without addition of macrophages (n=10); 2) A naïve group, with weekly intraperitoneal (ip) injection of 106 naïve macrophages per mouse (n=10); and 3) A tumor-educated group, with weekly ip injection of 106 tumor-educated macrophages per mouse (n=10). The study ended with termination of the tumor-educated group after 8 weeks due to a pre-morbid state identified in all mice. At this time, all mice in each of the three study arms were terminated, imaging was performed, and total tumor weight was obtained. In the control group, the average primary tumor weighed 668 mg; only three mice (30%) developed peritoneal metastases with an average weight of 241 mg. The naïve-macrophage group had an average tumor weight of 823 mg (p=0.51); 50% developed peritoneal metastases with an average weight of 975 mg (p=0.029). The tumor-educated-macrophage group had an average primary tumor weight of 2095 mg (p=0.001); 75% of mice developed peritoneal metastases with an average weight of 2135 mg (p=0.008). When comparing naïve- to tumor-educated- groups, primary tumor weight was significantly greater in the tumor-educated group (p=0.003), and the average weight of metastasis was 2.2 times greater in the tumor educated group, however this did not reach statistical significance (p = 0.17). When comparing naïve- to tumor-educated-groups, there was no statistically significant difference with regard to body weight (p=0.87), or weight of metastasis (p=0.68); however primary tumor weight was significantly greater in the tumor-educated group (p=0.013). Tumor-educated-macrophages specifically promote tumor growth progression in an orthotopic nude mouse model of pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1690. doi:1538-7445.AM2012-1690
The use of FL enables the identification of tumor foci that cannot be seen with standard laparoscopy. The technology described in this report has important potential for the clinical development of FL.
We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as “tumor-educated-macrophages” (Edu) and macrophages harvested from mice without tumors as “naïve-macrophages” (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.