Research

    Project 1: The ILLUMINATE Study

    Our clinical research team is conducting a Phase-2 clinical trial with a drug, pegsitacianine based on the fluorescent nanoparticles developed in our lab. This study is to investigate whether pegsitacianine can be used to image head and neck cancers as well as unknown primary cancers (UPC) of the head and neck after being given intravenously. More precise detection of unknown primary cancers and precise delineation of cancer margins can potentially assist surgeons intraoperatively and allow more complete tumor resections. The study is divided into 2 parts:

    Part 1

    Patients with visible head and neck cancer will be given pegsitacianine before undergoing oncologic surgery and imaged to detect cancer margins.

    Part 2

    Patients with unknown primary cancer (UPC) of the head and neck will be given pegsitacianine before undergoing exam under anesthesia or laryngoscopy intended to identify their primary cancer.

     

    For more details refer to the attached flyer and ClinicalTrials.gov, Identifier: NCT05576974. If you are interested in participating in the trial, please contact the Department of Otolaryngology by phone at research department at Email

    Reference:

    Fluorescent nanoprobe lights the way to reducing spread of cancer cells | Cancer | Discovery | ENT | UT Southwestern Medical Center 

    Selected publications:

    • Wang Y, Zhou K, Huang G, Hensley C, Huang X, Ma X, Zhao T, Sumer BD, DeBerardinis RJ, Gao J. A Nanoparticle-based Strategy for the Imaging of a Broad Range of Tumours by Nonlinear Amplification of Microenvironment Signals. Nat. Mater. 2014, 13, 204-212. PDF
    • Zhao T, Huang G,Yang S, Ramezani, S, Li Y, Wang Y, Ma X, Xie XJ, Thibodeaux J, Sun X, Sumer BD, Gao J. A Transistor-like pH Nanoprobe for Tumour Detection and Image-Guided Surgery. Nature Biomed. Eng. 2016, 1, 0006. (Featured by Science daily news, Dallas Morning News, NBC5, and CBS11) PDF
    • Huang G, Zhao T, Wang C, Nham K, Xiong Y, Gao X, Wang Y, Hao G, Ge WP, Sun XK, Sumer BD, Gao J. PET Imaging of Occult Tumours by Temporal Integration of Tumour-Acidosis Signals. Nature Biomed. Eng. 2020, 4, 314. PDF
    • Bennett ZT, Feng Q, Bishop JA, Huang G, Sumer BD, Gao J. Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles. Theranostics. 2020, 10(7), 3340-3350. PDF
    • Voskuil FJ, Steinkamp PJ, Zhao T, van der Begt B, Koller M, Doff JJ, Jayalakshmi Y, Hartung JP, Gao J, Sumer BD, Witjes MJH, van Dam GM. Exploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery. Nature Comm. 2020, 11, 3257. PDF
    Purple slide with heat spot

    Using a fluorescent camera during surgery, nanoparticles illuminate the tumor in this patient's tongue guiding the surgeon during the procedure.

    Project 2: Tumor Acidosis: Hallmark of Cancer

    Tumor Acidosis: Hallmark of Cancer

    Cancer cells are metabolically active and use the glycolytic pathway to generate energy, resulting in high uptake of glucose and preferential production of lactate (Warburg effect). Exportation of lactic acid/CO2 leads to a pH drop within the tumor microenvironment. Our lab has developed a series of pH-activatable fluorescence probes with different pH transitions attached to different fluorescent dyes, such as rhodamine, Cy5 or ICG. These pH-activatable fluorescence probes give us the ability to image tumors, study tumor acidosis (Warburg effect), and investigate the tumor immune microenvironment (TIME).

    Research Interest

    Surgical specimens collected from patients enrolled in our tissue biobank are used to study the tumor immune microenvironment (TIME) including the effects of acidosis on infiltrating immune cells. This is especially relevant to understanding the differences between HPV+ and HPV- squamous cell carcinoma since oropharyngeal cancers arise in tonsillar tissue that is immunologically active.

    Our Laboratory Tissue Biobank

    Our biological specimen repository has 10,000+ specimens from 900+ patients that are preserved using a variety of advanced techniques intended to allow long-term access to live cells, RNA, DNA and proteins from solid and liquid specimens. At the forefront of biomedical research, our repository serves as a pivotal resource for the collection, preservation, and distribution of high-quality specimens sourced from patients with head and neck malignancies and benign tumors. With a commitment to accelerating scientific discoveries, our repository plays a crucial role in facilitating interdisciplinary investigations, fostering collaborations, and ultimately paving the way for innovative therapies and personalized treatment strategies. All studies are compliant with the policies of the UT Southwestern Human Research Protection Program (HRPP) Department, are HIPAA compliant and IRB approved (STU 092013-032).

    Human tumor specimens treated with UPS nanoprobes (orange).

    Fig 1: To test the sensitivity and specificity of different nanoprobes: Human tumor tissue specimens treated with UPS nanoprobes (orange) . UPS activation map displays a heterogeneous pattern of extracellular acidity in the tumor microenvironment of patient samples.  A variety of UPS transition pH’s can be selected.

    T-cell infiltration(aqua) in the same cancer as well as expression of MCT-1 on cancer cells (yellow).Placeholder

    Fig 2: T-cell infiltration(aqua) in the same cancer as well as expression of MCT-1 on cancer cells (yellow).

    Project 3: Our Laboratory Tissue Biobank

    Our biological specimen repository has 10,000+ specimens from 900+ patients that are preserved using a variety of advanced techniques intended to allow long-term access to live cells, RNA, DNA and proteins from solid and liquid specimens. At the forefront of biomedical research, our repository serves as a pivotal resource for the collection, preservation, and distribution of high-quality specimens sourced from patients with head and neck malignancies and benign tumors. With a commitment to accelerating scientific discoveries, our repository plays a crucial role in facilitating interdisciplinary investigations, fostering collaborations, and ultimately paving the way for innovative therapies and personalized treatment strategies. All studies are compliant with the policies of the UT Southwestern Human Research Protection Program (HRPP) Department, are HIPAA compliant and IRB approved (STU 092013-032).

    Last updated 9/10/2024

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