Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo.

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137's cytostatic effect comparatively to other hematological malignancy cells. Flow cytometry cell cycle analysis revealed an increase in subG1 and G2/M populations after CBL0137 cell treatment, but the prevalent type of arrest varied. Apoptosis activation by CBL0137 measured by Annexin-V/PI dual staining was more active in AML and MM cells. RT2 PCR array showed that changes caused by CBL0137 in signaling pathways involved in cancer pathogenesis were more intensive in AML and MM cells. On the murine model of AML WEHI-3, CBL0137 showed significant anticancer effects in vivo, which were evaluated by corresponding changes in spleen and liver. Thus, more pronounced anticancer effects of CBL0137 in vitro were observed in respect to AML and MM. Experiments in vivo also indicated the perspective of CBL0137 use for AML treatment. This in accordance with the frontline treatment approach in AML using epigenetic drugs.

Lymphocyte subpopulations in melanoma patients treated with dendritic cell vaccines.

The main goal of cancer immunotherapy is to induce or boost tumor-specific effector cells able to eliminate or reduce tumor progression. In this study, we characterized lymphocyte phenotypes in melanoma patients receiving dendritic cell (DC)-based vaccinotherapy. We found that several biological markers served as unfavorable prognostic factors for patients' response to therapy. This included decrease of CD4+ and CD8+ lymphocyte levels, 10% and higher increase of CD16+CD3+CD8+ lymphocyte population, and increase of CD16+CD8+perforin+ T lymphocytes, especially in combination with decreased levels of CDI6+CD8(-)perforin+ and CD8+CD16(-)perforin+ cells. Increase in CD8+CD16(-)perforin+ T lymphocytes with normal levels of CD16+CD8(-)perforin+ cells and the absence of CD16+CD8+perforin+ and regulatory lymphocytes were shown to be the positive prognostic markers for patients' response to DC vaccines.