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Abstract The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR‐II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR‐II fluorophore, XW‐03‐66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW‐03‐66 self‐assembles into nanoparticles (≈80 nm) and has a systemic circulation half‐life ( t 1/2 ) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV‐ OSCC, XW‐03‐66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR‐II image‐guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications.
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Understanding Ductal Carcinoma In Situ Invasion using a Multiscale Agent-Based Model *
Ductal carcinoma in situ (DCIS) is commonly treated clinically through surgical resection. Although surgical options exist for resection, it is unclear which is optimal to reduce the likelihood of future invasive disease. This is further complicated by challenges in determining correct surgical margins from disease diagnostics, with mammographic imaging misidentifying surgical margins by as much as 2 cm vs. histological examination. We have implemented a threedimensional, hybrid multiscale model of DCIS to study disease initiation and progression. In order to shed new light on current biological questions and clinical challenges surrounding the disease, we present here an improved version of this model, with more biologically relevant molecular signaling pathways, cell phenotype hierarchies, and duct architecture variation. In particular, a cell necrosis, lysis and calcification pathway has been incorporated into the model to help better understand the relationship between diagnostic imaging and the true extent of disease invasion. We observe that deficiencies in availability of molecular signaling molecules that upregulate cell proliferation may be overcome by dynamic shifts in phenotypic distributions within the disease mass. Hypoxia, necrosis, and calcification together functioned as a hypoxia relief mechanism, and were observed to maintain a consistent distance between the DCIS leading edge and the site of necrosis onset, providing insights for improving surgical margins.
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- Award ID(s):
- 1716737
- PAR ID:
- 10097952
- Date Published:
- Journal Name:
- The 40th Annual International IEEE EMBS Conference
- Page Range / eLocation ID:
- 5846 to 5849
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1109/EMBC.2018.8513542
