A Minimal Fragment of MUC1 Mediates Growth of Cancer Cells

The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*1110, containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*1110 are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma

An Investigation on the Levels of Vascular Endothelial Growth Factor (VEGF) in the Unstimulated Whole Saliva of Patients with Recurrent Aphthous Stomatitis

Statement of Problem: Recurrent aphthous stomatitis (RAS) is one of the most common inflammatory diseases encountered in dental practice, but the precise etiology and pathogenesis of the disease is not fully understood. Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic cytokine involved in angiogenesis andwound healing. There is evidence that VEGF could play an important role in recruiting inflammatory infiltrates like those in RAS.Purpose: The aim of this study was to investigate salivary levels of VEGF in various stages of RAS.Materials and Methods: In a case/crossover study, salivary VEGF levels were determined in 31 patients with RAS. Their saliva was collected by the spitting method in specially prepared tubes in two stages; the active phase (first week) and the remission phase. Salivary levels were then determined using the Sandwich ELISA technique and the data were analyzed by the Wilcoxon test.Results: Patients in the remission period had increased VEGF values, 571.774(347.5499) pq/ml, as compared to the acute stage, 424.758 (235.1474), and the difference was significant (P< 0.05).Conclusion: Salivary VEGF levels seem to be associated with ulcer development in RAS, supporting the concept of a potential association between RAS and VEGF

Phytochemistry and bioactivity of Pedicularis sibthorpii growing in Iran

The methanol extract of the aerial parts of the medicinal plant Pedicularis sibthorpii Boiss., Scrophulariaceae, growing in the Azerbaijan province of Iran, was found to be active in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and the antibacterial agar well diffusion assays, but no general toxicity was observed in the brine shrimp lethality assay. A combination of solid-phase extraction (SPE) and preparative reversed-phase high-performance liquid chromatography (prep-RP-HPLC) analyses of the methanolic extract afforded three phenylethanoids (verbascoside, martynoside and isomartynoside), an iridoid (aucubin), a flavonoid (luteolin 7-O-&#946;-D-glucopyranoside) and mannitol, and the structures of these compounds were elucidated unambiguously by spectroscopic means. The distribution of the isolated compounds within the genus Pedicularis has also been discussed

Treatment efficacy modelling combining anti-PARP1 Olaparib® and fractioned irradiation on 3D Triple-Negative breast cancer cultures

International audienc