ABSTRACT
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype. RESULTS: Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031). CONCLUSIONS: Our study identified CRBP1 as a radiation-sensitive predictor in RC.
Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation , Gene Expression Regulation, Neoplastic/radiation effects , Promoter Regions, Genetic/genetics , Radiation Tolerance/genetics , Rectal Neoplasms/genetics , Retinol-Binding Proteins, Cellular/genetics , Blotting, Western , Cell Proliferation , Humans , Oligonucleotide Array Sequence Analysis , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Retinol-Binding Proteins, Cellular/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
Lipid metabolism in chylomicron and VLDL were examined in daunomycin-induced nephrotic rats. 1) There was no difference in intestinal cholesterogenesis between the control rats and daunomycin-induced nephrotic rats. 2) The apoprotein content of chylomicron and VLDL increased in daunomycin-induced nephrotic rats. 3) Daunomycin-induced nephrotic rats showed increases in the content of apo B-48 and C-III, and a decrease in that of apo E in chylomicron. The apoprotein composition of VLDL in daunomycin-induced nephrotic rats showed increased apo B and decreased apo E. These results suggest that increased chylomicron-cholesterol is not due to increased intestinal cholesterogenesis, but to decreased chylomicron catabolism in daunomycin-induced nephrotic rats. Increased apoprotein in VLDL may contribute to the decreased catabolism by reducing LPL activity in the plasma and increased secretion from the liver of daunomycin induced nephrotic rats.
Subject(s)
Chylomicrons/metabolism , Lipoproteins, VLDL/metabolism , Nephrotic Syndrome/metabolism , Animals , Apoproteins/metabolism , Cholesterol/metabolism , Chromatography, Agarose , Daunorubicin/adverse effects , Male , Nephrotic Syndrome/chemically induced , Rats , Rats, WistarABSTRACT
We describe a 43-year-old male patient with congenital antithrombin III deficiency requiring haemodialysis due to extension of venous thrombus from recurrent deep vein thrombosis. During dialysis with adequate heparinization, the patient often revealed clot formation in the extracorporeal circuit resulting in unexpected discontinuation of dialysis. When either a combination of antithrombin III concentrate plus heparin or the newly developed synthetic antithrombin preparation, MD805, was infused during dialysis, he could be uneventfully dialysed with either of the two regimens. The functional antithrombin III activity with MD805 increased to the same level as that obtained with antithrombin III concentrate, and it was possible to achieve an antithrombotic effect, as measured from the APTT and thrombin-antithrombin III complex with MD805 during and after dialysis. We thus found that MD805 could be used as an anticoagulant drug when an AT III-deficient patient required anticoagulation in the extracorporeal circulation.
