23 research outputs found

    Assessment of folate receptor-β expression in human neoplastic tissues

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    Over-expression of folate receptor alpha on cancer cells has been frequently exploited for delivery of folate-targeted imaging and therapeutic agents to tumors. Because limited information exists on expression of the beta isoform of the folate receptor in human cancers (FR-β), we have evaluated the immunohistochemical staining pattern of FR-β in 992 tumor sections from 20 different human cancer types using a new anti-human FR-β monoclonal antibody. FR-β expression was shown to be more pronounced in cells within the stroma, primarily macrophages and macrophage-like cells than cancer cells in every cancer type studied. Moreover, FR-β expression in both cancer and stromal cells was found to be statistically more prominent in females than males. A significant positive correlation was also observed between FR-β expression on stromal cells and both the stage of the cancer and the presence of lymph node metastases. Based on these data we conclude FR-β may constitute a good target for specific delivery of therapeutic agents to activated macrophages and that accumulation of FR-β positive macrophages in the stroma could serve as a useful indicator of a tumor's metastatic potential

    A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed

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    Apoptosis is generally believed to be a process thatrequires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the criticalroles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis invivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery. Palchaudhuri etal. describe the discovery of a small molecule called "Raptinal" that induces unusually rapid apoptotic cell death via the intrinsic pathway. Their work describes the utility of Raptinal as a tool for apoptosis induction relative to other available small molecules

    A High-Throughput Microtiter Plate Based Method for the Determination of Peracetic Acid and Hydrogen Peroxide

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    <div><p>Peracetic acid is gaining usage in numerous industries who have found a myriad of uses for its antimicrobial activity. However, rapid high throughput quantitation methods for peracetic acid and hydrogen peroxide are lacking. Herein, we describe the development of a high-throughput microtiter plate based assay based upon the well known and trusted titration chemical reactions. The adaptation of these titration chemistries to rapid plate based absorbance methods for the sequential determination of hydrogen peroxide specifically and the total amount of peroxides present in solution are described. The results of these methods were compared to those of a standard titration and found to be in good agreement. Additionally, the utility of the developed method is demonstrated through the generation of degradation curves of both peracetic acid and hydrogen peroxide in a mixed solution.</p></div

    Overview of selective hydrogen peroxide quantitation.

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    <p>A.) Chemical reaction between hydrogen peroxide and cerium (IV) sulfate. B.) Chemical reaction between peracetic acid and cerium (IV) sulfate. C.) Multiple wavelength cerium (IV) sulfate standard curve (n = 4). Error bars represent standard deviation and are typically smaller than the plotted marker.</p

    Comparison of hydrogen peroxide quantitation.

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    <p>The amount of hydrogen peroxide in various dilutions from a stock peracetic acid/hydrogen peroxide solution were determined via titration or the microtiter plate based method (n = 3, error bars represent standard deviation).</p

    Effect of sulfuric acid concentration on peroxide – potassium iodide reaction.

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    <p>A.) Various concentrations of sulfuric acid were used to react (A) 15 mM total peroxides with 250 mM potassium iodide or (B) only 250 mM potassium iodide (n = 3). Error bars represent standard deviation.</p
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