Cerulenin overcomes the protective effects of IL-6, IGF-1 and BMSCs on MM cell growth

(A, B, C) MM.1S and U266 cells were cultured for 48 h with the indicated concentrations [0 μmol/l (□), 3·15 μmol/l () 6·25 μmol/l (), 12·5 μmol/l ()] of Cerulenin, in the presence or absence of IL-6 (1 or 10 ng/ml: A), IGF-1 (10 or 50 ng/ml: B), or BMSC (C). Cell growth was assessed by [H]-thymidine uptake. Cerulenin inhibits MM cell growth and overcomes the stimulating effect of IL-6 (A) or IGF-1 (B) ( < 0·05), and BMSC ( < 0·05) (C). Values represent mean ± SD of quadruplicate cultures.<p><b>Copyright information:</b></p><p>Taken from "Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma"</p><p></p><p>British Journal of Haematology 2008;141(5):659-671.</p><p>Published online Jan 2008</p><p>PMCID:PMC2408665.</p><p>Journal compilation © 2008 Blackwell Publishing Ltd</p

Cerulenin induces apoptosis via activation of caspase-independent pathway

(A) MM.1S cells were cultured for 24 h with Cerulenin at the indicated doses. Induction of apoptosis by Cerulenin was determined by Apo2·7 staining and flow-cytometric analysis. (B) MM.1S cells were cultured with Cerulenin (50 μmol/l) for the indicated times (left panel), and preincubated with or without Z-VAD-FMK (50 μmol/l) for 1 h prior to treatment with Cerulenin for 12 h at the indicated doses (right panel). Total cell lysates (20 μg /lane) were subjected to Western blotting using anti-caspase -8, -9, -3, PARP, and α-tubulin Abs. FL, CF indicate the full length and cleaved form, respectively. (C, D) MM.1S cells were treated with the indicated dose of Cerulenin for 24 h, with or without Z-VAD-FMK (25 μmol/l or 50 μmol/l) 1 h pretreatment. Cytotoxicity was determined by MTT assay (C). Values represent mean ± SD of quadruplicate cultures. The percentage of apoptotic cells was determined by flow-cytometric analysis for APO2·7 staining (D). (E) Mitochondrial proteins AIF and Endo G were released into the cytosolic fraction from mitochondria after Cerulenin (50 μmol/l) treatment in MM.1S cells. Total cell lysates (20 μg/lane) were subjected to Western blotting using anti-AIF, Endo G, VDAC and α-tubulin Abs.<p><b>Copyright information:</b></p><p>Taken from "Retraction: Fatty acid synthase is a novel therapeutic target in multiple myeloma"</p><p></p><p>British Journal of Haematology 2008;141(5):659-671.</p><p>Published online Jan 2008</p><p>PMCID:PMC2408665.</p><p>Journal compilation © 2008 Blackwell Publishing Ltd</p

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers

<div><p>Background</p><p>Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD.</p><p>Methods</p><p>We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m²). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated.</p><p>Results</p><p>In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with <i>P</i> value < 0.05 (<i>CX3CR1</i> rs3732379, <i>SHROOM3</i> rs17319721, <i>MTP</i> rs1800591, <i>PIP5K1B</i> rs4744712, <i>APOA5</i> rs662799, <i>BRAP</i> rs3782886, <i>SPATA5L1</i> rs2467853, and <i>MCP1</i> rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, <i>BRAP</i> rs3782886 and <i>SPATA5L1</i> rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09–1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively).</p><p>Conclusions</p><p>After adjustment for clinical factors, kidney function was associated with <i>BRAP</i> rs3782886 and <i>SPATA5L1</i> rs2467853 and the GRS for CKD that we developed was associated CKD.</p></div

Multivariate linear regression analysis of the association between eGFR and SNPs.

<p>Multivariate linear regression analysis of the association between eGFR and SNPs.</p

Univariate and multivariate logistic regression analysis of SNP Score and CKD.

<p>Univariate and multivariate logistic regression analysis of SNP Score and CKD.</p

Clinical characteristics between the participants with or without chronic kidney disease.

<p>Clinical characteristics between the participants with or without chronic kidney disease.</p