Lung tumors with neuroendocrine morphology include typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The World Health Organization emphasizes the importance of mitotic count in differentiating these tumors. We studied the case of a 58-year-old male nonsmoker with recurrent pneumonia and an endobronchial mass, which was removed by right middle lobectomy. The patient was alive with no recurrent disease at 36-month follow-up. Histologically, the tumor showed well developed neuroendocrine morphology but contained up to 20 mitoses per 10 high-power fields and was therefore diagnosed as a large cell neuroendocrine carcinoma. However, several features, including the carcinoid-like morphology and endobronchial location of the tumor, absence of smoking history, and promising clinical course, were more characteristic of an atypical carcinoid than of a large cell neuroendocrine carcinoma. It may be necessary to redefine histologic criteria to allow a higher mitotic rate for classification as an atypical carcinoid.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/BF03033739 | DOI Listing |
Background: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Background: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFBackground: Accumulating evidence suggests that the presynaptic protein α-synuclein (α-syn), is involved in the pathophysiology of AD and elevated in the cerebrospinal fluid (CSF). The role of Natural Killer (NK) cells of the innate immune system in AD has largely been overlooked. In a murine model, depletion of NK cells augmented the accumulation of pathological α-syn.
View Article and Find Full Text PDFCurr Mol Med
January 2025
Medical Laboratory Technology Department, Beirut Arab University, Beirut, Lebanon.
Cancer stem cells (CSCs) are the key drivers of tumorigenesis and relapse. A growing body of evidence reveals the tremendous power of CSCs to directly resist innate and adaptive anti-tumor immune responses. The immunomodulatory property gives CSCs the ability to control the tumor immune microenvironment (TIME).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!