Detection of Barrett's neoplasia with a near-infrared fluorescent heterodimeric peptide.

Background: Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects.

Methods: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800.

Membrane Bound Peroxiredoxin-1 Serves as a Biomarker for Detection of Sessile Serrated Adenomas.

Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAF mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs .

Evidence of Duodenal Epithelial Barrier Impairment and Increased Pyroptosis in Patients With Functional Dyspepsia on Confocal Laser Endomicroscopy and "Ex Vivo" Mucosa Analysis.

Introduction: Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities.

Methods: This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18).

Per-oral Endoscopic Myotomy Biopsies of Achalasia Patients Reveal Schwann Cell Depletion in the Muscularis Propria.

Achalasia is a neurodegenerative condition resulting in abnormal lower esophageal sphincter relaxation and impaired upstream esophageal body peristalsis. The pathophysiology and natural history of achalasia remain unclear, and evaluation of the histopathogenesis of achalasia has traditionally been challenging because the esophageal wall muscularis propria is not typically accessible via routine endoscopic biopsies.

Integrated Imaging Methodology Detects Claudin-1 Expression in Premalignant Nonpolypoid and Polypoid Colonic Epithelium in Mice.

Objectives: Conventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa.

Methods: A peptide specific for claudin-1 is labeled with Cy5.

Autoimmune Gastritis.

Context.—: Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes.

Sorafenib encapsulated in nanocarrier functionalized with glypican-3 specific peptide for targeted therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with increasing incidence. Chemotherapy is required for HCC patients after receiving surgical resection. Serious off-target induced side effects and systemic toxicity limit the clinical utility of drugs.

Identification of Tumor Specific Peptide as EpCAM Ligand and Its Potential Diagnostic and Therapeutic Clinical Application.

Tumor targeting agents are being developed for early tumor detection and therapeutics. We previously identified the peptide SNFYMPL (SNF*) and demonstrated its specific binding to human esophageal specimens of high-grade dysplasia (HGD) and adenocarcinoma with imaging ex vivo. Here, we aim to identify the target for this peptide and investigate its potential applications in imaging and drug delivery.

Disrupting Inflammation-Associated CXCL8-CXCR1 Signaling Inhibits Tumorigenicity Initiated by Sporadic- and Colitis-Colon Cancer Stem Cells.

Dysfunctional inflammatory pathways are associated with an increased risk of cancer, including colorectal cancer. We have previously identified and enriched for a self-renewing, colon cancer stem cell (CCSC) subpopulation in primary sporadic colorectal cancers (CRC) and a related subpopulation in ulcerative colitis (UC) patients defined by the stem cell marker, aldehyde dehydrogenase (ALDH). Subsequent work demonstrated that CCSC-initiated tumors are dependent on the inflammatory chemokine, CXCL8, a known inducer of tumor proliferation, angiogenesis and invasion.

Approach to the Liver Biopsy in the Patient With Chronic Low-Level Aminotransferase Elevations.

Pathologists sometimes encounter a liver biopsy from an asymptomatic patient with unexplained low-level parenchymal liver enzyme elevations. These biopsies often have minor histologic changes but are otherwise almost entirely normal. This can lead to the quandary of whether or not the features are clinically meaningful and how one must formulate a diagnosis from the possibly nonspecific findings of a near-normal biopsy.

Mid- and Deep-Zone Gastritis: A Histologic Pattern Associated With Autoimmune Disease but Distinct From Autoimmune Atrophic Gastritis.

Objectives: We sought to characterize a histologic pattern of mid- and deep-zone gastritis, distinct from the typical pattern of Helicobacter pylori or autoimmune gastritis and to see if it had any clinicopathologic association(s).

Methods: We analyzed inflammatory patterns and composition, excluded autoimmune gastritis using immunohistochemistry, and reviewed the medical record for demographics, medical/surgical history, presenting symptoms, endoscopic findings, and medications for 28 cases.

Results: All cases had inflammation in the middle and/or deep mucosal zones with sparing of the superficial/pit compartment.

Multiplexed Targeting of Barrett's Neoplasia with a Heterobivalent Ligand: Imaging Study on Mouse Xenograft in Vivo and Human Specimens ex Vivo.

Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells.

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury.

The esophagus, a straight tube that connects the pharynx to the stomach, has the complex architecture common to the rest of the gastrointestinal tract with special differences that relate to its function as a conduit of ingested substances. For instance, it has submucosal glands that are unique and have a specific protective function. It has a squamous lining that exists nowhere else in the gut except the anus and it has a different submucosal nerve plexus when compared to the stomach and intestines.

Use of Appropriate Surveillance for Patients With Nondysplastic Barrett's Esophagus.

Background & Aims: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Guidelines recommend that patients with nondysplastic BE (NDBE) undergo surveillance endoscopy every 3-5 years. We aimed to identify factors associated with surveillance endoscopy of patients with NDBE and identify trends in appropriate surveillance endoscopy of NDBE at a large tertiary care center.

Melanoma induced immunosuppression is mediated by hematopoietic dysregulation.

Tumors are associated with expansion of immunosuppressive cells such as tumor associated macrophages (TAMs), regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). These cells promote tumor growth, angiogenesis, metastasis and immune escape. Cancer patients frequently present symptoms such as anemia, leukocytosis and/or cytopenia; associated with poor prognosis.

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia.

The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2.

In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide.

ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo.

Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy.

Background & Aims: Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients.

Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo.

Background & Aims: Conventional white-light colonoscopy aims to reduce the incidence and mortality of colorectal cancer (CRC). CRC has been found to arise from missed polypoid and flat precancerous lesions. We aimed to establish proof-of-concept for real-time endoscopic imaging of colonic adenomas using a near-infrared peptide that is specific for claudin-1.