Search results for "AEP"
showing 10 items of 115 documents
Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma
2021
A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…
IL-10 signaling prevents gluten-dependent intraepithelial CD4(+) cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine
2019
Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive. We have demonstrated that under homeostatic conditions in mice, gluten drives the differentiation of anti-inflammatory T cells producing large amounts of the immunosuppressive cytokine interleukin-10 (IL-10). Here we addressed whether this dominant IL-10 axis prevents gluten-depend…
Galectin-3 Released by Pancreatic Ductal Adenocarcinoma Suppresses γδ T Cell Proliferation but Not Their Cytotoxicity
2020
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment with a dense desmoplastic stroma. The expression of β-galactoside-binding protein galectin-3 is regarded as an intrinsic tumor escape mechanism for inhibition of tumor-infiltrating T cell function. In this study, we demonstrated that galectin-3 is expressed by PDAC and by γδ or αβ T cells but is only released in small amounts by either cell population. Interestingly, large amounts of galectin-3 were released during the co-culture of allogeneic in vitro expanded or allogeneic or autologous resting T cells with PDAC cells. By focusing on the co-culture of tumor cells and γδ T cells, we obse…
Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity
2020
Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in …
Novel Insight Into the Molecular and Metabolic Mechanisms Orchestrating IL-17 Production in γδ T Cells
2019
Increasing evidence has demonstrated that IL-17-producing γδ T cells (γδ T17) play a tumor-promoting role in a series of cancers via various mechanisms in mice and human cancers, though the relationship between γδ T17 and human tumors has yet to be extensively characterized and established. Molecular signals such as intrinsic cascade, environmental cues and cellular metabolic pathways including nutrient uptake and utilization in γδ T17 cells are significantly important for their activation, differentiation, and function. Understanding the molecular mechanisms and metabolic pathways of γδ T17 cells in both the physiological setting and tumor environment would contribute to the development of…
Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data
2021
Background: Syndecan-1 (CD138
Auditory-evoked potentials to changes in sound duration in urethane-anesthetized mice
2019
Spectrotemporally complex sounds carry important information for acoustic communication. Among the important features of these sounds is the temporal duration. An event‐related potential called mismatch negativity indexes auditory change detection in humans. An analogous response (mismatch response) has been found to duration changes in speech sounds in rats but not yet in mice. We addressed whether mice show this response, and, if elicited, whether this response is functionally analogous to mismatch negativity or whether adaptation‐based models suffice to explain them. Auditory‐evoked potentials were epidurally recorded above the mice auditory cortex. The differential response to the chang…
Perspectives of Chromo and Magnifying Endoscopy
2003
The goal of every routine endoscopy in the gut is the early diagnosis of malignant and premalignant changes of the mucosa. Chromo- and magnifying endoscopes are exciting new tools and offer detailed analysis of the colonic mucosal surface and pit pattern architecture. This review summarizes recent advances in endoscopic characterization of colorectal lesions using magnification endoscopy and chromoendoscopy. Surface analysis of the colon using chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions with high specificity. The precise delineation of the borders and a more detailed macroscopic analysis of the lesions are further advantages. In particular, flat adenoma…
Chromoendoscopy in Inflammatory Bowel Disease
2012
Chromoendoscopy with methylene blue or indigo carmine significantly increases the diagnostic yield of finding intraepithelial neoplasia in patients with longstanding colitis. The number needed to treat is 14 for panchromoendoscopy to identify 1 additional patient with dysplasia. Chromoendoscopy can greatly facilitate the identification of flat lesions harboring intraepithelial neoplasia. Chromoendoscopy can guide biopsies and clearly reduces the amount of biopsies that are needed per patient. Magnifying endoscopy or CLE are additional techniques, which can be used in conjunction with chromoendoscopy to further reduce the amount of biopsies and to further increase the diagnostic yield. Chrom…
Evolving endoscopic strategies for detection and treatment of neoplastic lesions in inflammatory bowel disease
2013
The paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology. Modern technology has demonstrated a remarkably improved capacity to detect and characterize subtle neoplastic lesions. As such, practices of obtaining interval random biopsy specimens to identify “invisible”neoplasia and of recommending total proctocolectomy for treatment of early neoplastic lesions are gradually being phased out. Further research is required to confirm the safety and effectiveness of endoscopic resection of more advanced neoplastic lesions, including DALMs and lesions bearing HG-IEN. Moving forward, studies evaluating CRC risk profiles in IBD patients wou…