Phase I trial of selenium plus chemotherapy in gynecologic cancers

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Phase I trial of selenium plus chemotherapy in gynecologic cancers Mihae Song, Muthu N. Kumaran, Murugesan Gounder, Darlene G. Gibbon, Wilberto Nieves-Neira, Ami Vaidya, Mira Hellmann, Michael P. Kane, Brian Buckley, Weichung Shih, Paula B. Caffrey, Gerald D. Frenkel, Lorna Rodriguez-Rodriguez Gynecologic Oncology Volume 150, Issue 3, Pages 478-486 (September 2018) DOI: 10.1016/j.ygyno.2018.07.001 Copyright © 2018 Terms and Conditions

Fig. 1 Alterations in gene and protein expression following treatment with selenious acid plus chemotherapy. A. Genes up- and down-regulated following treatment with selenium plus chemotherapy. Shown are only those genes which exhibited an increase or decrease in expression in all samples tested by microarray analysis (i.e., breast and ovarian cancer cell lines, as well as patient tumor specimens) following exposure to selenious acid plus chemotherapy compared with the control samples. CASP3: Caspase 3; ABCD3: ATP-binding cassette, sub-family D (ALD), member 3; RAD51AP1: RAD51 associated protein 1; CCNE2: Cyclin E2; SLC26A2: Solute carrier family 26, member 2; CENPF: Centromere protein F; NPL: N-acetylneuraminate pyruvate lyase; WBP4: WW domain binding protein 4; GLI3: Glioma-associated oncogene family zinc finger 3; HIST1H3G: Histone Cluster 1 H3 family member G; HIST1H2BG: Histone cluster 1 H2B family member G; DIP2C: Disco interacting protein 2 homolog C; LTBP3: Latent transforming growth factor beta binding protein 3. B. Downregulation of RAD51AP1 protein expression in the presence of selenious acid plus carboplatin. Western blot of MCF-7/Adr cells showing changes in RAD51AP1 protein expression following treatment with selenious acid, carboplatin, and the combination of selenious acid and chemotherapy. C. Quantification of Western blot image shown in Fig. 1B using ImageJ software (https://imagej.nih.gov/ij/) available from NIH. The corrected (e.g., background subtracted) integrated densities of the RAD51AP1 bands are plotted at three carboplatin concentrations with (red bars) and without selenious acid (blue bars). Results are normalized with respect to the integrated density of the RAD51AP1 band under conditions of 30 μM carboplatin without selenious acid (set at 100%). Gynecologic Oncology 2018 150, 478-486DOI: (10.1016/j.ygyno.2018.07.001) Copyright © 2018 Terms and Conditions

Fig. S1 Plasma elemental selenium concentration in different dose cohorts in cycle 1 (n = 5; 800 μg), (n = 3; 1000 μg), (n = 5; 1200 µg), (n = 3; 2000 μg); (n = 4; 5000 μg). A. Plasma selenium concentration-time profile at different dose cohorts. B. Baseline concentration subtracted (stripped) plasma selenium concentration-time profile at different dose cohorts. Gynecologic Oncology 2018 150, 478-486DOI: (10.1016/j.ygyno.2018.07.001) Copyright © 2018 Terms and Conditions

Fig. S2 Kaplan-Meier curve of progression-free survival in subgroup of patients (n = 28) with stage III/IV ovarian/fallopian tube/peritoneal cancers. Gynecologic Oncology 2018 150, 478-486DOI: (10.1016/j.ygyno.2018.07.001) Copyright © 2018 Terms and Conditions