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Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.

Takahashi R, Yamagishi M, Nakano K, Yamochi T, Yamochi T, Fujikawa D, Nakashima M, Tanaka Y, Uchimaru K, Utsunomiya A, Watanabe T - Cancer Sci. (2014)

Bottom Line: Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells.The HH inhibitors are suggested as drug candidates for ATL therapy.Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

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Related in: MedlinePlus

GANT61 treatment reduced cell viabilities of primary ATL samples. (a) Effect of GANT61 in primary PBMC samples. The PBMC from healthy donors (n = 7), asymptomatic carriers (n = 3) and ATL patients (n = 5) were exposed in 5 μM of GANT61 for 72 h. Cells were maintained in media with 1% self-serum. **P < 0.01. (b) GANT61-dependent apoptosis in ATL samples. The PBMC from healthy donors (n = 4) and ATL patients (n = 4) were treated with 5 μM of GANT61 for 72 h. Graphs show percentiles of apoptotic popula-tion in CD4+ cells **P < 0.01.
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fig07: GANT61 treatment reduced cell viabilities of primary ATL samples. (a) Effect of GANT61 in primary PBMC samples. The PBMC from healthy donors (n = 7), asymptomatic carriers (n = 3) and ATL patients (n = 5) were exposed in 5 μM of GANT61 for 72 h. Cells were maintained in media with 1% self-serum. **P < 0.01. (b) GANT61-dependent apoptosis in ATL samples. The PBMC from healthy donors (n = 4) and ATL patients (n = 4) were treated with 5 μM of GANT61 for 72 h. Graphs show percentiles of apoptotic popula-tion in CD4+ cells **P < 0.01.

Mentions: Finally, we evaluated the pharmacological activity of GANT61 on primary ATL samples. Although GANT61 did not show a clear effect on PBMC derived from healthy donors and HTLV-1 carriers, its treatment specifically reduced the viability of ATL samples significantly (Fig.7a). Flow cytometry demonstrated that GANT61 specifically killed CD4+ leukemic cells from ATL patients via apoptosis induction (Fig.7b).


Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.

Takahashi R, Yamagishi M, Nakano K, Yamochi T, Yamochi T, Fujikawa D, Nakashima M, Tanaka Y, Uchimaru K, Utsunomiya A, Watanabe T - Cancer Sci. (2014)

GANT61 treatment reduced cell viabilities of primary ATL samples. (a) Effect of GANT61 in primary PBMC samples. The PBMC from healthy donors (n = 7), asymptomatic carriers (n = 3) and ATL patients (n = 5) were exposed in 5 μM of GANT61 for 72 h. Cells were maintained in media with 1% self-serum. **P < 0.01. (b) GANT61-dependent apoptosis in ATL samples. The PBMC from healthy donors (n = 4) and ATL patients (n = 4) were treated with 5 μM of GANT61 for 72 h. Graphs show percentiles of apoptotic popula-tion in CD4+ cells **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4462393&req=5

fig07: GANT61 treatment reduced cell viabilities of primary ATL samples. (a) Effect of GANT61 in primary PBMC samples. The PBMC from healthy donors (n = 7), asymptomatic carriers (n = 3) and ATL patients (n = 5) were exposed in 5 μM of GANT61 for 72 h. Cells were maintained in media with 1% self-serum. **P < 0.01. (b) GANT61-dependent apoptosis in ATL samples. The PBMC from healthy donors (n = 4) and ATL patients (n = 4) were treated with 5 μM of GANT61 for 72 h. Graphs show percentiles of apoptotic popula-tion in CD4+ cells **P < 0.01.
Mentions: Finally, we evaluated the pharmacological activity of GANT61 on primary ATL samples. Although GANT61 did not show a clear effect on PBMC derived from healthy donors and HTLV-1 carriers, its treatment specifically reduced the viability of ATL samples significantly (Fig.7a). Flow cytometry demonstrated that GANT61 specifically killed CD4+ leukemic cells from ATL patients via apoptosis induction (Fig.7b).

Bottom Line: Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells.The HH inhibitors are suggested as drug candidates for ATL therapy.Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus