A5102729927- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Esophageal Cancer Research and Treatment
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Nanoplatforms for cancer theranostics
- Photoacoustic and Ultrasonic Imaging
- Colorectal Cancer Screening and Detection
- Gastric Cancer Management and Outcomes
- Glycosylation and Glycoproteins Research
- Cancer Research and Treatments
- Diabetes and associated disorders
- Advanced Fluorescence Microscopy Techniques
- T-cell and B-cell Immunology
- Photodynamic Therapy Research Studies
- Gut microbiota and health
- Advanced Breast Cancer Therapies
- Helminth infection and control
- Genetic factors in colorectal cancer
- Gastrointestinal Tumor Research and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Biosensors and Analytical Detection
- Colorectal Cancer Surgical Treatments
- HER2/EGFR in Cancer Research
- Metastasis and carcinoma case studies
Baylor College of Medicine
2023-2024
Agenus (United States)
2023-2024
University of Michigan
2011-2021
Michigan United
2011-2017
Michigan Medicine
2012-2016
Air Force Medical University
2010
A fluorescently labeled peptide enables first-in-human targeted endoscopic imaging of esophageal neoplasia.
Abstract Conventional immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) elicit durable survival but primarily in patients with immune-inflamed tumors. Although the mechanisms underlying response to anti–CTLA-4 remain poorly understood, Fc-gamma receptor (FcγR) IIIA coengagement seems critical for activity, potentially explaining modest clinical benefits of approved antibodies. We demonstrate that engineered enhanced FcγR affinity leverages FcγR-dependent...
Cancer is one of the major causes mortality and morbidity in our healthcare system. Molecular imaging an emerging methodology for early detection cancer, guidance therapy, monitoring response. The development new instruments exogenous molecular probes that can be labeled multi-modality critical to this process. Today, at a crossroad, targeted agents are expected broadly expand ability detect manage cancer. This integrated strategy will permit clinicians not only localize lesions within body...
Gastrointestinal cancers are heterogeneous and can overexpress several protein targets that be imaged simultaneously on endoscopy using multiple molecular probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide-field fluorescence detection of colonic dysplasia. Excitation at 440, 532, 635 nm is delivered into single spiral fiber, collected by ring light-collecting optical fibers placed around the instrument periphery. Specific-binding peptides selected with phage...
Colorectal cancer (CRC) is a major cause of cancer-related deaths in much the world. Most CRCs arise from pre-malignant (dysplastic) lesions, such as adenomatous polyps, and current endoscopic screening approaches with white light do not detect all dysplastic lesions. Thus, new strategies to identify including non-polypoid are needed. We aim validate novel peptides that specifically target colonic epithelium vivo. used phage display peptide binds mucosa vivo genetically engineered mouse...
<h3>Objective</h3> To demonstrate a near-infrared (NIR) peptide that is highly specific for colonic adenomas on fluorescence endoscopy in vivo. <h3>Design</h3> A 3 mm diameter endoscope was adapted to deliver 671 nm illumination and collect NIR (696–736 nm). Target (QPIHPNNM) control (YTTNKH) peptides were labelled with Cy5.5, dye, characterised by mass spectra. The topically administered separately (100 μM) through the endoscope9s instrument channel into distal colon of <i>CPC;Apc</i> mice,...
<b>Background and study aims:</b> To demonstrate the clinical use of a multimodal endoscope with targeted fluorescently labeled peptide for quantitative detection Barrett's neoplasia. <b>Patients methods:</b> We studied 50 patients esophagus using prototype peptide. Co-registered fluorescence reflectance images were converted to ratios correct differences in distance geometry over image field view. The ratio segmented unique threshold that maximized variance between high low intensities...
We report the development, characterization, and validation of a peptide specific for extracellular domain HER2. This probe chemistry was developed molecular imaging by using structural model to select an optimal combination amino acids that maximize likelihood unique hydrophobic hydrophilic interactions with HER2 3. The sequence KSPNPRF identified conjugated either FITC or Cy5.5 via GGGSK linker Fmoc-mediated solid-phase synthesis demonstrate flexibility this chemical structure be labeled...
Colorectal cancer initially lies dormant as dysplasia, a premalignant state that provides an opportunity for early detection. Dysplasia can be flat in morphology, focal size, and patchy distribution, thus it appears "invisible" on conventional wide-field endoscopy.We aim to develop validate peptide is specific epidermal growth factor receptor (EGFR), cell surface target overexpressed colonic adenomas readily accessible imaging.We expressed purified the extracellular domain of EGFR use with...
Improved methods for early cancer detection arising from Barrett’s oesophagus (BE) are still needed. Imaging molecular expression patterns in BE patients can target neoplasia. We demonstrate a multiplexed fluorescence imaging approach to detect premalignant lesions with two fluorescently labeled heptapeptides specific EGFR and ErbB2. Twenty-two underwent endoscopic multimodal scanning fiber endoscope (mmSFE). In this pilot study, 92% of neoplastic could be imaged by comparison pathology,...
Conventional white-light colonoscopy aims to reduce the incidence and mortality of colorectal cancer (CRC). CRC has been found arise from missed polypoid flat precancerous lesions. We aimed establish proof-of-concept for real-time endoscopic imaging colonic adenomas using a near-infrared peptide that is specific claudin-1.
We demonstrate a handheld multiphoton endomicroscope with 3.4 mm distal diameter that can repetitively image mouse colon in vivo.A 2D resonant MEMS mirror was developed to perform beam scanning Lissajous pattern.The instrument has an effective numerical aperture of 0.63, lateral and axial resolution 2.03 9.02 μm, respectively, working distance 60 field-of-view 300 × μm 2 .Hoechst injected intravenously mice stain cell nuclei.We were able collect histology-like images vivo at 5 frames/sec,...
We demonstrate vertical cross-sectional (XZ-plane) images of near-infrared (NIR) fluorescence with a handheld dual axes confocal endomicroscope that reveals specific binding Cy5.5-labeled peptide to pre-malignant colonic mucosa. This view is perpendicular the tissue surface, and similar used by pathologists. The scan head 10 mm in outer diameter (OD), integrates one dimensional (1-D) microelectromechanical systems (MEMS) X-axis scanner bulky lead zirconate titanate (PZT) based Z-axis...
EGFR is a promising cell surface target for in vivo imaging that highly overexpressed hepatocellular carcinoma (HCC), common cancer worldwide. Peptides penetrate easily into tumors deep imaging, and clear rapidly from the circulation to minimize background. We aim demonstrate use of an specific peptide detect HCC xenograft mice with photoacoustic imaging. Nude implanted human cells overexpress were injected intravenously Cy5.5-labeled scrambled control peptides respectively. Photoacoustic...