G2-phase arrest through p21(WAF1 / Cip1) induction and cdc2 repression by gnidimacrin in human hepatoma HLE cells.

Gnidimacrin (NSC252940) shows significant antiproliferating activity against human tumor cell lines. This compound binds to and directly activates protein kinase C (PKC). Human hepatoma HLE cells, which lose p53 function and retinoblastoma protein (Rb) expression, are resistant to gnidimacrin.

Interleukin (IL)-4 promotes T helper type 2-biased natural killer T (NKT) cell expansion, which is regulated by NKT cell-derived interferon-gamma and IL-4.

CD1d-restricted natural killer T (NKT) cells can rapidly produce T helper type 1 (Th1) and Th2 cytokines and also play regulatory or pathological roles in immune responses. NKT cells are able to expand when cultured with alpha-galactosylceramide (alpha-GalCer) and interleukin (IL)-2 in a CD1d-restricted manner. However, the expansion ratio of human NKT cells is variable from sample to sample.

Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells.

Pironetin, isolated from Streptomyces sp., is a potent inhibitor of microtubule assembly and the first compound identified that covalently binds to alpha-tubulin at Lys352. We examined whether pironetin is an effective agent against human small cell lung cancer H69 cells, including two cell lines resistant to the microtubule-targeted drugs vindesine (H69/VDS) and paclitaxel (H69/Txl) that interact with beta-tubulin.

Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Valpha14 natural killer T cells.

Mouse natural killer T cells with an invariant Valpha14-Jalpha18 TCR rearrangement (Valpha14i NKT cells) are able to regulate immune responses through rapid and large amounts of Th1 and Th2 cytokine production. It has been reported that in vivo administration of the Valpha14i NKT cell ligand, alpha-galactosylceramide (alpha-GalCer) significantly reduced morbidity and mortality of acute graft-versus-host disease (GVHD) in mice. In this study, we examined whether adoptive transfer of in vitro-expanded Valpha14i NKT cells using alpha-GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells of C57BL/6 mice into (B6xDBA/2) F(1) mice.

Phenotypical and functional alterations during the expansion phase of invariant Valpha14 natural killer T (Valpha14i NKT) cells in mice primed with alpha-galactosylceramide.

Invariant Valpha14 natural killer T (Valpha14i NKT) cells are a unique immunoregulatory T-cell population that is restricted by CD1d. The glycolipid alpha-galactosylceramide (alpha-GalCer) is presented by CD1d and causes robust Valpha14i NKT-cell activation. Three days after injection of alpha-GalCer, Valpha14i NKT cells vigorously increase in number and then gradually decrease to normal levels.

Cytokine production and migration of in vitro-expanded NK1.1(-) invariant Valpha14 natural killer T (Valpha14i NKT) cells using alpha-galactosylceramide and IL-2.

Mouse natural killer T cells with invariant Valpha14 rearrangement (Valpha14i NKT cells) can rapidly produce both Th1 and Th2 cytokines and regulate various immune responses, such as autoimmunity and tumor immunity. In this study, we describe the phenotypical and functional characterization of in vitro-expanded mouse Valpha14i NKT cells from spleen using a combination of alpha-galactosylceramide (alpha-GalCer) and IL-2. The expanded Valpha14i NKT cells retained the memory/activated (CD44(+)CD69(+)CD62L(-)) and CD4(+) or CD4(-)8(-) double negative phenotypes but modulated or lost the classical NKT cell marker, NK1.

The mouse natural killer T cell-associated antigen recognized by U5A2-13 monoclonal antibody is intercellular adhesion molecule-1.

Natural Killer T (NKT) cells in mice are generally defined as NK1.1(+) T cells, although NK1.1 antigen is expressed only in C57BL/6 and related strains.

U5A2-13, an antigen originally found on mouse NK-like T cells, is an early inducible cell surface antigen during lymphoid activation.

We have previously reported a monoclonal antibody (mAb), U5A2-13 mAb, which originally recognizes a phenotypically and functionally similar population of natural killer (NK)-like T cells. In this study, we found that U5A2-13 antigen (U5A2-13) was expressed not only on NK-like T cells but also on T and B cells during activation. In contrast to the low levels of U5A2-13 on freshly harvested T and B cells, the activation of these cells by various stimuli resulted in high levels of expression of U5A2-13 in vitro and in vivo.

Involvement of PKC betaII in anti-proliferating action of a new antitumor compound gnidimacrin.

Daphnane-type diterpene gnidimacrin (NSC 252940) shows significant antitumor activity against murine tumors and human tumor cell lines. This compound binds to and directly activates protein kinase C (PKC), arresting the cell cycle at the G(1) phase through inhibition of cdk2 activity in human K562 leukemia cells. In our study, we examined whether cellular PKC is involved in the antiproliferating effect of gnidimacrin.

Squamocin-O(1) and squamocin-O(2), new adjacent bis-tetrahydrofuran acetogenins from the seeds of Annona squamosa.

Two bis-tetrahydrofuran acetogenins, squamocin-O(1) (1) and squamocin-O(2) (2), were isolated from a MeOH extract of seeds of Annona squamosa L. Their structures were determined by spectral means including precursor-ion scanning mass spectral analysis for their aminal derivatives. The configurations at the oxymethine chiral centers were assigned as 12R,15R,16R,19R,20R,23R,24S,28S,36S for 1 and 12S,15R,16R,19R,20R,23R,24S, 28S,36S for 2, based on 1H NMR analysis of their Mosher's ester derivatives and CD data.