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Advances in Brief

The Histone Deacetylase Inhibitor, CBHA, Inhibits Growth of Human Neuroblastoma Xenografts in Vivo, Alone and Synergistically with All-Trans Retinoic Acid

Dennis C. Coffey, Martha C. Kutko, Richard D. Glick, Lisa M. Butler, Glenn Heller, Richard A. Rifkind, Paul A. Marks, Victoria M. Richon and Michael P. La Quaglia
Dennis C. Coffey
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Martha C. Kutko
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Richard D. Glick
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Lisa M. Butler
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Glenn Heller
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Richard A. Rifkind
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Paul A. Marks
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Victoria M. Richon
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Michael P. La Quaglia
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DOI:  Published May 2001
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    Fig. 1.

    s.c. growth of the SMS-KCN-69n neuroblastoma xenograft in SCID mice treated with daily i.p. injections of vehicle (Control), atRA alone, or CBHA (50, 100, or 200 mg/kg) alone or combined with atRA. The dose of atRA was 2.5 mg/kg. Bars, mean tumor volume ± SE. Measurements were obtained every 2–3 days during the 3-week treatment course (total of nine measurements). Tumor volumes for days 1, 6, 11, 16, and 21 are shown. Tumors were implanted 7 days before the start of treatment. Treatment commenced on day 1, when the average tumor volume was 91 ± 2.7 mm3.

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    Fig. 2.

    Effect of treatment with CBHA and atRA on hematopoiesis in SCID mice bearing SMS-KCN-69n human neuroblastoma xenografts. Complete blood counts were obtained upon death on the final day of treatment for 3 or 4 animals from each group. P was not significant for each parameter across all groups by ANOVA (see text). WBC count (WBC) is expressed in thousands, hemoglobin (Hgb) as gm/dl, and platelets (Plt) as the value × 105.

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    Fig. 3.

    Accumulation of acetylated core histone H3 in SMS-KCN-69n neuroblastoma xenografts after administration of CBHA. Tumors were excised from mice on the final day of treatment, ∼2 h after the final i.p. injection of vehicle (Control) or 50, 100, or 200 mg/kg CBHA (column headings), and histones were isolated. Acetylation of histone H3 was analyzed by Western blotting of histone samples using antibodies to acetylated histone H3 (top panel). Two separate tumors are shown for each dose. Coomassie Blue-stained polyacrylamide gel of the histone samples (bottom panel) controls for protein loading variation.

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    Group average weight changes for the eight experimental groups

    Weights were obtained three times/week throughout the treatment course. The beginning and ending weights are shown, as well as the average change in grams and percentages.
    CBHA (mg/kg)RA (mg/kg)Start weightaFinal weightaChange (%)b P c
    0023.8 ± 0.7626 ± 0.842.2 (9)
    02.526.1 ± 0.7726.3 ± 0.800.2 (0)0.04
    50022.7 ± 0.8524.4 ± 0.711.7 (7)0.81
    502.526.7 ± 1.0425.6 ± 0.75−1.1 (−4)<0.01
    100028.2 ± 1.3427.9 ± 1.32−0.3 (−1)<0.01
    1002.525.3 ± 0.6724.6 ± 0.58−0.7 (−2)<0.01
    200027.1 ± 0.924.9 ± 0.79−2.2 (−8)<0.01
    2002.527.2 ± 0.825.4 ± 0.78−1.8 (−6)<0.01
    • a All values are presented as the mean ± SE in grams for each treatment group. Initial and final body weights refer to the weight of the mice at the start of treatment and at the end of the study (day 21), respectively, with tumors in situ.

    • b Weight change is listed as the difference between the group mean final and the initial weights in grams with the percent change in parentheses.

    • c The P indicates whether the distribution of average weight change was significantly different from that of control. Derived by the nonparametric Wilcoxon rank-sum test.

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Cancer Research: 61 (9)
May 2001
Volume 61, Issue 9
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The Histone Deacetylase Inhibitor, CBHA, Inhibits Growth of Human Neuroblastoma Xenografts in Vivo, Alone and Synergistically with All-Trans Retinoic Acid
Dennis C. Coffey, Martha C. Kutko, Richard D. Glick, Lisa M. Butler, Glenn Heller, Richard A. Rifkind, Paul A. Marks, Victoria M. Richon and Michael P. La Quaglia
Cancer Res May 1 2001 (61) (9) 3591-3594;

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The Histone Deacetylase Inhibitor, CBHA, Inhibits Growth of Human Neuroblastoma Xenografts in Vivo, Alone and Synergistically with All-Trans Retinoic Acid
Dennis C. Coffey, Martha C. Kutko, Richard D. Glick, Lisa M. Butler, Glenn Heller, Richard A. Rifkind, Paul A. Marks, Victoria M. Richon and Michael P. La Quaglia
Cancer Res May 1 2001 (61) (9) 3591-3594;
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