A new marine-derived macrolide designated as neopeltolide (1) has been isolated from a deep-water sponge of the family Neopeltidae. Its structure was elucidated on the basis of spectroscopic data interpretation. Neopeltolide (1) is a potent inhibitor of the in vitro proliferation of the A-549 human lung adenocarcinoma, the NCI-ADR-RES human ovarian sarcoma, and the P388 murine leukemia cell lines, with IC50's of 1.2, 5.1, and 0.56 nM, respectively. Neopeltolide (1) also inhibited the growth of the fungal pathogen Candida albicans with a minimum inhibitory concentration of 0.62 microg/mL.

Leiodermatolide is a structurally unique macrolide, isolated from the deep-water marine sponge Leiodermatium sp., which exhibits potent antiproliferative activity against a range of human cancer cell lines (IC50 <10 nM) and dramatic effects on spindle formation in mitotic cells. Its unprecedented polyketide skeleton and stereochemistry were established using a combination of experimental and computational (DP4) NMR methods, and molecular modelling.

The purpose of this study was to determine whether constitutive NF-kappaB activity regulates the expression level of interleukin-8 (IL-8) in metastatic human melanoma cells. Cultures of metastatic human A375 melanoma cells expressed higher levels of IL-8 mRNA and protein than nonmetastatic A375 human melanoma cells. No discernible differences in IL-8 half-life were found between metastatic and nonmetastatic cells, but cells that overexpressed IL-8 had a higher transcription rate and increased IL-8 promoter activity. Analysis of the IL-8 promoter using deletion mutants revealed that the region within -133 was essential for constitutive IL-8 promoter activity and that mutation of NF-kappaB binding sites eliminated the constitutive IL-8 promoter activity. The activation of constitutive IL-8 transcription directly correlated with the level of constitutive NF-kappaB activity. Transfection of melanoma cells with a dominant-negative mutant IkappaBalpha expression vector (pLXSN-IkappaBalphaM) significantly decreased the level of constitutive NF-kappaB activity and expression of IL-8, demonstrating that constitutive NF-kappaB/relA activities contribute to overexpression of IL-8 in highly metastatic human melanoma cells.

IntroductionBreast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult.MethodsNon-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls.ResultsDespite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3–4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3–4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males.DiscussionThese results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted.