Browsing by Subject "window chamber"

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    A Novel Preclinical Murine Model to Monitor Inflammatory Breast Cancer Tumor Growth and Lymphovascular Invasion.
    (Cancers, 2023-04) Rickard, Ashlyn G; Sannareddy, Dorababu S; Bennion, Alexandra; Patel, Pranalee; Sauer, Scott J; Rouse, Douglas C; Bouchal, Samantha; Liu, Harrison; Dewhirst, Mark W; Palmer, Gregory M; Devi, Gayathri R
    Inflammatory breast cancer (IBC), an understudied and lethal breast cancer, is often misdiagnosed due to its unique presentation of diffuse tumor cell clusters in the skin and dermal lymphatics. Here, we describe a window chamber technique in combination with a novel transgenic mouse model that has red fluorescent lymphatics (ProxTom RFP Nu/Nu) to simulate IBC clinicopathological hallmarks. Various breast cancer cells stably transfected to express green or red fluorescent reporters were transplanted into mice bearing dorsal skinfold window chambers. Intravital fluorescence microscopy and the in vivo imaging system (IVIS) were used to serially quantify local tumor growth, motility, length density of lymph and blood vessels, and degree of tumor cell lymphatic invasion over 0-140 h. This short-term, longitudinal imaging time frame in studying transient or dynamic events of diffuse and collectively migrating tumor cells in the local environment and quantitative analysis of the tumor area, motility, and vessel characteristics can be expanded to investigate other cancer cell types exhibiting lymphovascular invasion, a key step in metastatic dissemination. It was found that these models were able to effectively track tumor cluster migration and dissemination, which is a hallmark of IBC clinically, and was recapitulated in these mouse models.
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    Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo.
    (Proc Natl Acad Sci U S A, 2014-04-15) Juhas, Mark; Engelmayr, George C; Fontanella, Andrew N; Palmer, Gregory M; Bursac, Nenad
    Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration.
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    Optical imaging of immune response following synergistic immune photothermal therapy (SYMPHONY) for bladder cancer using a murine window chamber model
    (2020) Wang, Yuxiang

    Cancer is a significant threat to human health with more than eight million deaths each year in the world. Therefore, numerous technologies have been implemented or under development to effectively treat cancer.

    One novel therapeutic platform is implemented using nanoparticle-mediated photothermal therapy. Gold NanoStars (GNS), are a unique form of gold nanoparticles (GNPs) that have unique therapeutic potential because of their star-shaped geometry. Enhanced light absorption and higher photon-to-heat conversion efficiency are introduced by GNS’s plasmonic properties. In the application of hyperthermia, this photothermal process can be exploited to specifically heat tumors and, more importantly, to amplify the antitumor immune response following the highly immunogenic thermal death of cancer cells. Meanwhile, when combined with immune checkpoint inhibition immunotherapy (IT), this SYnergistic iMmuno PHOtothermal NanotherapY (SYMPHONY) has been shown to reverse tumor-mediated immunosuppression, thereby leading to the treatment of not only primary tumors but also cancer metastasis. This phenomenon is called the “abscopal effect”. However, the immune response has not been clearly quantified yet. Our hypothesis was that different treatment modalities (PTT only, GNS-PTT, IT, SYMPHONY) will trigger different levels of immune response including the decrease of immunosuppressive cells and the influx of cytotoxic cells, which could be observed by imaging immune cell reporters.

    Accordingly, two specific aims were set for this study: 1. to develop a pre-clinical murine model to quantify different levels of immune response mimicking the tumor metastatic environment; 2. to quantify immune response following SYMPHONY using imaging analysis techniques.

    To achieve the specific aims, window chamber models combined with in vivo fluorescence imaging techniques provide an ideal platform to mimic cancer metastasis in the chamber and longitudinally monitor immune response through the prevalence of fluorescent reporters specifically localized to immune cells of interest. We utilized a dual tumor mouse model, consisting of a primary tumor grown in the flank of the mouse which received the SYMPHONY therapy, as well as a secondary tumor located in the window chamber through which we could image and observe the abscopal response to therapy. In this study, we demonstrate the optical imaging procedure following synergistic immune photothermal therapy (SYMPHONY) of bladder cancer using the immune-GFP-labeled murine window chamber model, for the purpose of quantifying the immune response at this mimicked-tumor metastasis site. Four groups were established: the SYMPHONY group, the photothermal therapy group, the immune therapy group, and the Gold NanoStars (GNS) control group.

    Higher immune responses were observed in the tumor regions compared to the non-tumor regions. The in vivo fluorescence imaging along with the window chamber technique demonstrates the feasibility and convenience of following such a longitudinal study like SYMPHONY. However, although temporal changes in reporter intensity were observed, with a limited number of samples, we cannot thus far identify significant differences among the treatment groups. Approaches for further characterizing this model are discussed.