55 research outputs found

    Nanodiamond as a New Hyperpolarizing Agent and Its <sup>13</sup>C MRS

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    In this work, we have hyperpolarized carbonaceous nanoparticles (<i>D</i> ā‰ˆ 10 nm), that is, ā€œnanodiamondsā€, with 1.1% <sup>13</sup>C (natural abundance) using dynamic nuclear polarization (DNP). The polarization buildup curve showed a signal enhancement with relative intensity up to 4700 at 1.4 K and 100 mW microwave power. <sup>13</sup>C magnetic resonance spectra (MRS) were obtained from the sample at 7 T, and the signal decayed with a <i>T</i><sub>1</sub> of 55 Ā± 3s. Notably, polarization was possible in the absence of added radical, consistent with previous results showing endogenous unpaired electrons in natural nanodiamonds. These likely contribute to the shorter <i>T</i><sub>1</sub>ā€™s compared to those of highly pure diamond. Despite the relatively short <i>T</i><sub>1</sub>, these observations suggest that natural nanodiamonds may be useful for in vivo applications

    Ī”R2* calculated from normal tissue in a single mouse acquired on three different days.

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    <p>In this case, first- and second- pass circulation of CA injection is observed. Only first ā€“pass circulation was used in DSC analysis.</p

    Drug Resistance and Cellular Adaptation to Tumor Acidic pH Microenvironment

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    Despite advances in developing novel therapeutic strategies, a major factor underlying cancer related death remains resistance to therapy. In addition to <i>biochemical</i> resistance, mediated by xenobiotic transporters or binding site mutations, resistance can be <i>physiological</i>, emerging as a consequence of the tumorā€™s physical microenvironment. This review focuses on extracellular acidosis, an end result of high glycolytic flux and poor vascular perfusion. Low extracellular pH, pHe, forms a physiological drug barrier described by an ā€œion trappingā€ phenomenon. We describe how the acid-outside plasmalemmal pH gradient negatively impacts drug efficacy of weak base chemotherapies but is better suited for weakly acidic therapeutics. We will also explore the physiologic changes tumor cells undergo in response to extracellular acidosis which contribute to drug resistance including reduced apoptotic potential, genetic alterations, and elevated activity of a multidrug transporter, p-glycoprotein, pGP. Since low pHe is a hallmark of solid tumors, therapeutic strategies designed to overcome or exploit this condition can be developed

    VIFs from Gd-DTPA (a) and P792 (c).

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    <p>VIFs were smoothed by temporal spline-fit function for Gd-DTPA (b) and P792 (d).</p

    Signal amplitude change of DSC on tumor tissue (left column) and normal tissue (right column).

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    <p>Three rows represent three separate measurements (top row: Day 1; middle row: Day 3; bottom row: Day 5) for a single animal. The 95% confidence limits for significant changes in signal are shown on each graph (dot line), The bolus was injected at 0 seconds.</p

    SU86.86 cells exhibit phenotypic and genotypic changes following selection by IH.

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    <p>SU86.86 cells were treated with IH for 50 cycles, had clonal populations raised, and grown in normoxia for 2 months. A significant decrease in expression of E-cadherin (A) and p53 (B) was detected by quantitative Real-Time PCR. IH-selected SU86.86 clones also exhibited an increase in resistance to etoposide (C) and hypoxia (D).Results of selection of RKO cells following IH-selection (E-H). We do not detect any changes in p53 or E-cadherin expression within clones of RKO IH-selected (E,F). Furthermore, these cells did not exhibit resistance to etoposide (G), nor hypoxia (H).</p

    Selection of MCF10A cells by intermittent hypoxia (IH) induces drug resistance and reduced expression of p53 and E-cadherin.

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    <p>(A) Multiple intermittent hypoxia regimens were tested at 1%O<sub>2</sub> and 0.2% O<sub>2</sub> over 6 days. Factor survival is expressed as compared to cells grown in parallel in normoxia (21%O<sub>2</sub>). MCF10A cells undergoing repetitive cycles of 16 hours hypoxia followed by 8 hrs reoxygenation exhibited the most cell death. (B) MCF10A cells were cultured in 50 cycles of IH in the selective regimen described in (A), and individual cells were isolated to be raised as clones, and then passaged for 2 months in normoxia. These clonal populations were tested for etoposide resistance. Heterogeneity in the IH-selected clones was detected, while a significant overall increase in etoposide resistance was measured. (C) MCF10A IH-selected clones 4 and 9 were further tested for resistance to multiple cytotoxic conditions, including treatment to the microtubule stabilizing docetaxel, the folate metabolism inhibitor methotrexate, as well as hypoxia and reduction of growth factors. Intermittent hypoxia exhibited increased survival to all of these conditions except for survival to growth factor removal. (D,E) Intermittent hypoxia exhibits changes in the expression of p53 and E-cadherin. Quantitative Real-Time PCR was performed on each IH-selected and passage control clone. Reduced <i>p53</i> and E-cadherin mRNA expression levels were detected in IH-selected control clones. Factor expression is relative to the average of control clones.</p
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