Immunomodulatory Synthetic Glycocluster Molecule Prevents Melanoma Growth In Vivo.

Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster and a transmembrane macrophage activator independent of the mannose receptor. TADM induces Th1-type immune responses and suppresses Th2-type cytokines in acute and chronic allergic inflammation models in vivo. We, therefore, wanted to test whether TADM could also facilitate anti-tumour tissue responses similar to what has been observed for the immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4.

Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin.

Therapeutic protocols including EGFR antibodies in the context of oxaliplatin-based regimens have variable clinical effect in colorectal cancer. Here, we tested the effect of the EGFR antibody cetuximab in different sequential combinations with oxaliplatin on the growth of colorectal cancer cells in vitro and in vivo. Cetuximab reduced the efficacy of oxaliplatin when administered before oxaliplatin but provided additive effect when administered after oxaliplatin regardless of the KRAS or BRAF mutation status of the cells.

Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity-dependent manner.

Dual specificity phosphatase-3 (Dusp3/Vhr) regulates cell cycle progression by counteracting the effects of mitogen-activated protein kinases (Mapk) Erk1/2 and Jnk. Despite the known upregulation of Dusp3 at M phase in mammalian cells, its mitotic functions are poorly characterized. Here, we report that loss of Dusp3 by RNAi leads to the formation of multipolar spindles in human mitotic cancer cells in an Erk1/2-dependent manner.

Centmitor-1, a novel acridinyl-acetohydrazide, possesses similar molecular interaction field and antimitotic cellular phenotype as rigosertib, on 01910.Na.

Mitosis is an attractive target for the development of new anticancer drugs. In a search for novel mitotic inhibitors, we virtually screened for low molecular weight compounds that would possess similar steric and electrostatic features, but different chemical structure than rigosertib (ON 01910.Na), a putative inhibitor of phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathways.

Loss of Pax5 promotes plasma cell differentiation.

Pax5 is indispensable for the commitment of early lymphoid progenitors to the B cell lineage as well as for the development of B cells. To better understand the functional importance of Pax5 at the later stages of B cell differentiation, we established a Pax5-deficient DT40 B cell line. The Pax5(-/-) cells exhibited slower growth, decreased surface IgM expression, and total loss of B cell receptor signaling.

Ikaros has a crucial role in regulation of B cell receptor signaling.

The transcription factor Ikaros, a key regulator of hematopoiesis, has an essential role in lymphocyte development. In mice, fetal lymphoid differentiation is blocked in the absence of Ikaros, and whereas T cells develop postnatally, B cells are totally absent. The significance of Ikaros in the B cell development is evident, but how Ikaros regulates B cell function has neither been established nor previously been studied with B cells that lack Ikaros expression.