Image_1_Expert guidance on prophylaxis and treatment of dermatologic adverse events with Tumor Treating Fields (TTFields) therapy in the thoracic region.pdf

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used with other cancer treatment modalities. The most common AE associated with TTFields therapy is mild-to-moderate skin events, which can be treated with topical agents and may be managed without significant treatment interruptions. Currently, there are no guidelines for oncologists regarding the management of TTFields therapy-related skin AEs in the thoracic region, applicable for patients with pleural mesothelioma or NSCLC. This publication aims to provide guidance on preventing, minimizing, and managing dermatologic AEs in the thoracic region to help improve patient quality of life and reduce treatment interruptions that may impact outcomes with TTFields therapy.</p

Image_2_Expert guidance on prophylaxis and treatment of dermatologic adverse events with Tumor Treating Fields (TTFields) therapy in the thoracic region.pdf

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used with other cancer treatment modalities. The most common AE associated with TTFields therapy is mild-to-moderate skin events, which can be treated with topical agents and may be managed without significant treatment interruptions. Currently, there are no guidelines for oncologists regarding the management of TTFields therapy-related skin AEs in the thoracic region, applicable for patients with pleural mesothelioma or NSCLC. This publication aims to provide guidance on preventing, minimizing, and managing dermatologic AEs in the thoracic region to help improve patient quality of life and reduce treatment interruptions that may impact outcomes with TTFields therapy.</p

Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0353-2">https://link.springer.com/article/10.1007/s12325-016-0353-2</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Principal cell ablation increases hemolymph phosphate and decreases life span, rescue by addition of sevelamer to the culture medium.

<p>A, B: Micrographs of 10 days old males with expression of GFP (green) in principal cells (<b>A</b>) or females with expression of GFP along with <i>reaper</i> (<i>rpr</i>) in principal cells after culture for ten days at 29°C (<b>B</b>). Epifluorescent microphotograph (10X) of tubule and gut of the same genotypes shown in A+B. Ablation of GFP-positive cells (green) by <i>rpr</i> is nearly complete with the exception of a few segments as shown schematically in the inset. As a consequence when compared to <i>rpr</i>-negative tubules (<b>C</b>), the majority of the tubule stained with propidium iodide (red) is made up of GFP-negative cells in (<b>D</b>). Median life span (<b>E</b>, n = 60–120 per condition) or hemolymph phosphate concentration (<b>F</b>, n = 3 with collections from 15 flies) of females expressing <i>rpr</i> or <i>GFP</i>-RNAi in principal cells after culture on standard medium containing 30 mM sodium phosphate (P30) normalized when cultured on 1% sevelamer (Sev1%) for 14 days.</p

RNAi-mediated inhibition of MAPK-signaling <i>in vivo</i> decreases hemolymph phosphate. A:

<p>The most advanced developmental stage with induced knockdown was scored on standard medium (1 = embryonic, 2 = first and second instar larva, 3 = third instar larva, 4 = pupal lethal, 4.5 = developmental delay, adult, 5 = adult). <b>B:</b> hemolymph phosphate concentration of young adult females cultured at 29°C for five days, and <b>C:</b> median life span of adult males cultured at 29°C on standard medium (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753.s010" target="_blank">Table S1</a>). <b>a:</b> p<0.05, <b>b:</b> p<0.007 vs. Luc/GFP/white controls. P<0.017 was used to test for multiple comparisons between three treatments.</p

Significant outliers in development, life span, and hemolymph phosphate.

<p><i>Drosophila</i> gene names for developmental lethal mutants and outliers in life span and hemolymph phosphate assays shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone-0056753-g006" target="_blank">Figures 6</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone-0056753-g007" target="_blank">7</a>. Significance for longevity and hemolymph phosphate is based on Student’s t-test (p<0.05). Bold script indicates genes that remain significant after Bonferroni’s correction for multiple comparisons when we used p<0.003 for the life span assay based on 17 outliers and when we used p<0.007 and p<0.0125 for the hemolymph assay based on seven and four outliers, respectively. Underline script is used for longer/higher outliers, while regular script is used for shorter/lower outliers. (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753.s010" target="_blank">Table S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone-0056753-g007" target="_blank">Figs. 7</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone-0056753-g008" target="_blank">8</a> for detailed results).</p

Phosphate supplementation or inhibitors of phosphate uptake influences adult life span.

<p>Median life span of adult <i>y w</i> males cultured on standard medium (SM): Control (C, n = 550), 30 mM sodium phosphate (P30, n = 465), 30 mM sodium sulfate (S30, n = 245), 1% sevelamer (Sev1, n = 207), 1 mM phosphonoformic acid (PFA1, n = 130), and the combinations: Sev1+P30 (n = 115), PFA1+P30 (n = 137), or defined medium (DM) supplemented with 1.5, 27, or 53 mM sodium phosphate (P1.5, n = 202; P27, n = 200; P53, n = 194). P<0.005 was used to test for multiple comparisons between eleven treatments.</p

S2R+ genome-wide RNAi screen. A:

<p>heatmap of z-scores for 146 verified genes, cell count/well based on DAPI signal (first column), dpERK signal after 10 min. phosphate stimulation (middle column), and dpERK signal after 10 min. insulin stimulation (third column), green indicates positive regulators, red indicates negative regulators. <b>B:</b> Functional classification of 146 verified genes based on GO term categories using the DAVID tool (<a href="http://david.abcc.ncifcrf.gov/" target="_blank">http://david.abcc.ncifcrf.gov/</a>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753-Huangda1" target="_blank">[27]</a>, and FlyMine (<a href="http://www.flymine.org/" target="_blank">www.flymine.org/</a>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753-Lyne1" target="_blank">[28]</a>. <b>C:</b> Number of genes identified in prior DRSC screens.</p

<i>In vivo</i> secondary screen using the <i>da</i>-<i>Gal4</i>^ts as driver identifies genetic modifiers of <i>Drosophila</i> larval development, and adult hemolymph phosphate and lifespan.

<p><b>A:</b> Developmental stage on standard medium, <b>B:</b> hemolymph phosphate concentration of young adult females cultured at 29°C for five days, and % change of life span on standard medium supplemented with 1% sevelamer (<b>C</b>), or 30 mM sodium phosphate (<b>D</b>) when compared to standard medium alone (<b>E</b>) (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753.s010" target="_blank">Table S1</a>).</p

Adult hemolymph phosphate, phosphate excretion and whole fly Pi. A:

<p>Excretion of phosphate after culture of <i>y w</i> females for five days on standard medium (C) alone or supplemented with 1% sevelamer (Sev1%) and 30 mM sodium phosphate (P30) (n = 3 pooled collections of 15–20 flies). <b>B:</b> hemolymph phosphate concentration (n = 3 pooled collections of 15 flies) and <b>C:</b> whole fly phosphate (n = 10) of flies cultured as described for A. Note that <i>y w</i> and CS flies have lower hemolymph phosphate concentrations than OR and <i>w¹¹¹⁸</i> flies and the F1 generation females that express control RNAis (see Methods and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056753#pone.0056753.s005" target="_blank">Fig. S5</a>), which is likely due to differences in genetic background.</p