TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.

Glioma-initiating cells (GICs) are responsible for the initiation and recurrence of gliomas. Here, we identify a molecular mechanism that regulates the self-renewal capacity of patient-derived GICs. We show that TGF-beta and LIF induce the self-renewal capacity and prevent the differentiation of GICs.

High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene.

TGFbeta acts as a tumor suppressor in normal epithelial cells and early-stage tumors and becomes an oncogenic factor in advanced tumors. The molecular mechanisms involved in the malignant function of TGFbeta are not fully elucidated. We demonstrate that high TGFbeta-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma.

Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells.

We determined differentially expressed genes in HT29 human colon cancer cells, both after short treatment with methotrexate (MTX) and after the resistance to MTX had been established. Screening was performed using Atlas Human Cancer 1.2K cDNA arrays.

Sensitization of human erythroleukemia K562 cells resistant to methotrexate by inhibiting IMPDH.

Background: Methotrexate (MTX) is an inhibitor of dihydrofolate reductase (DHFR), an enzyme involved in nucleotide synthesis, and is widely used in therapy, but its efficacy is often compromised by the development of resistance in cancer cells. To identify potential targets as modulators in MTX chemotherapy, we determined gene expression profiles upon MTX treatment.

Material/methods: Expression profiles in human erythroleukemia K562 cells were determined after short treatment with MTX or once resistance to MTX was established.

Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells.

We performed a functional genomic analysis to study the effect of epicatechin and polyphenolic cocoa extract in the human colon adenocarcinoma cell line Caco-2. The specific Human Hematology/Immunology cDNA arrays by Clontech, containing 406 genes in duplicate, were used. The differentially expressed genes were classified according to their level of expression, calculated as the ratio of the value obtained after each treatment relative to control cells, with a statistical significance of P < 0.

Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages.

With the aim of identifying new target genes that could contribute to limit foam cell formation, we analyzed changes in the pattern of gene expression in human THP-1 macrophages treated with atorvastatin and oxidized-LDL (oxLDL). To this end, we used a human cDNA array containing 588 cardiovascular-related cDNAs. Exposure to oxLDL resulted in differential expression of 26 genes, while coincubation with atorvastatin modified the expression of 29 genes, compared to treatment with oxLDL alone.

The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors.

We examined the effect of suboptimal concentrations of cyclin-dependent kinase inhibitors, which do not interfere with cell proliferation, on retinoblastoma expression in hamster (Chinese hamster ovary K1) and human (K562 and HeLa) cells. To achieve this, we used the chemical inhibitors roscovitine and olomoucine (which inhibit CDK2 preferentially), UCN-01 (which also inhibits CDK4/6) and p21 (as an intrinsic inhibitor). All chemical inhibitors and overexpression of p21 strongly induced retinoblastoma protein expression.