20 research outputs found
Mass Homozygotes Accumulation in the NCI-60 Cancer Cell Lines As Compared to HapMap Trios, and Relation to Fragile Site Location
Runs of homozygosity (ROH) represents extended length of homozygotes on a long genomic distance. In oncology, it is known as loss of heterozygosity (LOH) if identified exclusively in cancer cell rather than in matched control cell. Studies have identified several genomic regions which show consistent ROH in different kinds of carcinoma. To query whether this consistency can be observed on broader spectrum, both in more cancer types and in wider genomic regions, we investigated ROH patterns in the National Cancer Institute 60 cancer cell line panel (NCI-60) and HapMap Caucasian healthy trio families. Using results from Affymetrix 500 K SNP arrays, we report a genome wide significant association of ROH regions between the NCI-60 and HapMap samples, with much a higher level of ROH (11 fold) in the cancer cell lines. Analysis shows that more severe ROH found in cancer cells appears to be the extension of existing ROH in healthy state. In the HapMap trios, the adult subgroup had a slightly but significantly higher level (1.02 fold) of ROH than did the young subgroup. For several ROH regions we observed the co-occurrence of fragile sites (FRAs). However, FRA on the genome wide level does not show a clear relationship with ROH regions
Multifaceted link between cancer and inflammation
10.1042/BSR20100136Bioscience Reports3211-15BRPT
Marine compounds inhibit growth of multiple myeloma in vitro and in vivo
Purpose: The prognosis of patients with multiple myeloma (MM) is still dismal
despite recent improvements achieved by introducing new therapeutic agents.
However, there remains an urgent need for progress in myeloma drug development.
We here show that novel marine-derived compounds can exert potent anti-myeloma
activity.
Experimental Design: Nine marine-derived compounds were applied at low nM
concentrations (0.1-100 nM) to MM cell lines (OPM-2, NCI-H929, U266, RPMI-8226),
to primary human myeloma cells and to peripheral blood mononuclear cells. Apoptosis
was determined by flow cytometry. In addition, eGFP-transgenic MM cell lines
growing with mesenchymal cells from bone marrow were used to visualize tumors
by fluorescence stereomicroscopy. Anti-myeloma activities were studied in vitro in
3D spheroids and in vivo in myeloma xenografts on chicken embryos. Tumor size was
analyzed by measuring GFP content with a GFP ELISA. Anti-angiogenic activities of
compounds were tested in an in vivo gelatin sponge assay with conditioned media
from primary bone marrow-derived endothelial cells.
Results: We identified a subset of marine compounds with strong anti-myeloma
activity in vitro and in vivo. Moreover, some of the compounds inhibited myelomarelated
angiogenesis in the in vivo gelatin sponge assay. They merit further drug
development to improve treatment options for MM
Combined CXCR3/CXCR4 measurements are of high prognostic value in chronic lymphocytic leukemia due to negative co-operativity of the receptors.
Lignans and sesquiterpene lactones from Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae)
Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds
(hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of
Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-
2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-
2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranosyl-2′-O-methacrylate,
(7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-7,8,7′,8′-tetrahydronaphtho [8,8′-c]furan-1(3H)-one, and
(7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-3′,4′-dihydroxy-8'-(hydroxymethyl)-7,8,7′,8′-tetrahydronaphthalen-8-carboxylic
acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and
D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-
3′,4′-dihydroxy-7,8,7′,8′-tetrahydronaphtho [8,8′-c]furan-1(3H)-one and (7S,8R,8′R)-7-(3,4-dihydroxyphenyl)-
3′,4′-dihydroxy-8'-(hydroxymethyl)-7,8,7′,8′-tetrahydronaphthalen-8-carboxylic acid were determined
using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-
3-carboxy-O-β-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma
cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100mM against MM1S strain. No neurotoxicity
was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-
3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring
neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-
(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, hypochoeroside D,
and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD.
Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-
(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside and sesquiterpene lactone hypochoeroside
C